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In response to the pressing global challenge of antibiotic resistance, time efficient design and synthesis of novel antibiotics are of immense need. Polycyclic polyprenylated acylphloroglucinols (PPAP) were previously reported to effectively combat a range of gram‐positive bacteria. Although the exact mode of action is still not clear, we conceptualized a late‐stage divergent synthesis approach to expand our natural product‐based PPAP library by 30 additional entities to perform SAR studies against methicillin‐resistant Staphylococcus aureus (MRSA). Although at this point only data from cellular assays are available and understanding of molecular drug‐target interactions are lacking, the experimental data were used to generate 3D‐QSAR models via an artificial intelligence training and to identify a common pharmacophore model. The experimentally validated QSAR model enabled the estimation of anti‐MRSA activities of a virtual compound library consisting of more than 100,000 in‐silico generated B PPAPs, out of which the 20 most promising candidates were synthesized. These novel PPAPs revealed significantly improved cellular activities against MRSA with growth inhibition down to concentrations less than 1 μm. [ABSTRACT FROM AUTHOR]

Assessing bacterial communities across water resources is crucial for understanding ecological dynamics and improving water quality management. This study examines the functional profiles of bacterial communities in drinking water resources in Mega Manila, Philippines, including Laguna Lake tributaries, pre-treatment plant sites, groundwater sources, and post-treatment plant sites. Using eDNA sequencing, flux balance analysis, and taxonomy-to-phenotype mapping, we identified metabolic pathways involved in nutrient metabolism, pollutant degradation, antibio- tic synthesis, and nutrient cycling. Despite site variations, there are shared metabolic pathways, suggesting the influence of common ecological factors. Site-specific differences in pathways like ascorbate, aldarate, and phenylalanine metabolism indicate localized environmental adaptations. Antibiotic synthesis pathways, such as streptomycin and polyketide sugar unit biosynthesis, were detected across sites. Bacterial communities in raw and pre-treatment water showed potential for pollutant degradation such as for endocrine-disrupting chemicals. High levels of ammonia-oxidizing and sulfate-reducing bacteria in pre- and post-treatment water suggest active nitrogen removal and pH neutralization, indicating a need to reassess existing water treatment approaches. This study underscores the adaptability of bacterial communities to environmental factors, as well as the importance of considering their functional profiles in assessing drinking water quality resources in urban areas. [ABSTRACT FROM AUTHOR]

Soil microbiomes play a pivotal role in shaping plant health and their ability to suppress the pathogens. However, the specific microbial features that confer disease suppression in agricultural soils have remained unknown. In this study, we aim to elucidate the mechanistic roles of soil key bacteria contributing to disease suppression in banana Panama disease by using a comprehensive soil survey focusing on suppressive, and conducive soils. Through an initial field survey across twelve paired locations, we identified five fields with significantly lower pathogen abundances compared to their co-located counterparts. Subsequent greenhouse experiments validated the disease-suppressive nature of soils collected from Jianfeng (JF) and Lingao (LG), both exhibiting low pathogen densities. Furthermore, four OTUs classified as Massilia (OTU44), Flavisolibacter (OTU396), Brevundimonas (OTU632) and Pseudomonas (OTU731), respectively, were identified as key players in suppressing pathogen invasion as they were significantly enriched in suppresive groups and pathogen inoculated treatments. The present results might suggest a vital link between these soil bacteria and pathogen inhibition in banana rhizosphere via a greenhouse experiment. The abundance of nonribosomal peptide synthetase (NRPS) genes, which was responsible for antibiotic synthesis and significantly enriched in the banana rhizosphere after beneficial microorganism inoculation, displayed a significant and negative correlation with pathogen abundance while a positive correlation with relative abundance of Pseudomonas. This result suggests that the up-regulation of NRPS genes may play a key role in bolstering banana plant immunity. These findings not only provide promising biocontrol strategies but also offer valuable insights into the dynamic relationship between soil microbiomes and plant physiology, paving the way for sustainable agriculture and disease management. [ABSTRACT FROM AUTHOR]

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic–AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity. [ABSTRACT FROM AUTHOR]

Coevolutionary antagonism generates relentless selection that can favour genetic exchange, including transfer of antibiotic synthesis and resistance genes among bacteria, and sexual recombination of disease resistance alleles in eukaryotes. We report an unusual link between biological conflict and DNA transfer in bdelloid rotifers, microscopic animals whose genomes show elevated levels of horizontal gene transfer from non-metazoan taxa. When rotifers were challenged with a fungal pathogen, horizontally acquired genes were over twice as likely to be upregulated as other genes — a stronger enrichment than observed for abiotic stressors. Among hundreds of upregulated genes, the most markedly overrepresented were clusters resembling bacterial polyketide and nonribosomal peptide synthetases that produce antibiotics. Upregulation of these clusters in a pathogen-resistant rotifer species was nearly ten times stronger than in a susceptible species. By acquiring, domesticating, and expressing non-metazoan biosynthetic pathways, bdelloids may have evolved to resist natural enemies using antimicrobial mechanisms absent from other animals. Fungi and bacteria fight coevolutionary wars using antimicrobial compounds that animal cells cannot usually produce. This study finds that bdelloid rotifers attacked by a fungal pathogen express genes acquired horizontally from bacteria, including some resembling antibiotic synthesis clusters. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of biocompatible three different maleic anhydride co-polymer conjugated with two different beta-lactam antibiotics at in vitro conditions were conducted. The polymer–drug conjugates were synthesized by coupling β-lactam antibiotics via amide bonds to the copolymer. In this work, six different drug-functionalized maleic anhydride copolymers (DFMACs) were synthesized by the chemical conjugation method. This method is based on the ring-opening reaction of the anhydride ring of the copolymer to form an amide bond linking the drug. The synthesized DFMACs were characterized by 1H NMR and FTIR/ATR spectroscopies and analyses were carried out by UV/VIS spectroscopy and Zeta-sizer instrument in detail with consecutive antibacterial tests. The existence of a newly formed amide covalent bond between the drug and the copolymer chains was confirmed by 1H NMR and FTIR/ATR studies. This is the first report on the application of the selected branched biodegradable polymeric matrices for the covalent conjugation of ampicillin and cefalexin. Optimum stability and activity conditions for the synthesized DFMACs were determined. Analyses were conducted under in vitro conditions including varying pH values and simulated body fluids as a function of time to obtain new drug delivery system candidates for the two different antibiotics. [ABSTRACT FROM AUTHOR]

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense Tropical Race 4 (Foc TR4), poses a significant threat to banana production globally, thereby necessitating effective biocontrol methods to manage this devastating disease. This study investigates the potential of Bacillus siamensis strain JSZ06, isolated from smooth vetch, as a biocontrol agent against Foc TR4. To this end, we conducted a series of in vitro and in vivo experiments to evaluate the antifungal activity of strain JSZ06 and its crude extracts. Additionally, genomic analyses were performed to identify antibiotic synthesis genes, while metabolomic profiling was conducted to characterize bioactive compounds. The results demonstrated that strain JSZ06 exhibited strong inhibitory activity against Foc TR4, significantly reducing mycelial growth and spore germination. Moreover, scanning and transmission electron microscopy revealed substantial ultrastructural damage to Foc TR4 mycelia treated with JSZ06 extracts. Genomic analysis identified several antibiotic synthesis genes, and metabolomic profiling revealed numerous antifungal metabolites. Furthermore, in pot trials, the application of JSZ06 fermentation broth significantly enhanced banana plant growth and reduced disease severity, achieving biocontrol efficiencies of 76.71% and 79.25% for leaves and pseudostems, respectively. In conclusion, Bacillus siamensis JSZ06 is a promising biocontrol agent against Fusarium wilt in bananas, with its dual action of direct antifungal activity and plant growth promotion underscoring its potential for integrated disease management strategies. [ABSTRACT FROM AUTHOR]

Hirudo nipponia is an important medicinal animal in China. Its salivary gland secretions contain a variety of protein bioactive substances. Investigations of its salivary glands are of great significance in the study of the medicinal value and mechanism of leech secretions. Illumina RNA-Seq technology was used to perform transcriptome sequencing of salivary gland tissue of H. nipponia under starvation (D30) and fed (D0) states. A total of 2,650 differentially expressed genes (DEGs) were screened. Using the label-free protein quantification technique and bioinformatics analysis, the expression of differentially expressed proteins (DEPs) in the salivary gland tissue of H. nipponia was compared. A total of 2,021 proteins were identified, among which 181 proteins were differentially expressed between the starvation and fed states, with 72 significantly upregulated and 109 significantly downregulated. The salivary glands of H. nipponia synthesized protein-based active substances after 30 days of starvation and adapted to the starvation environment by weakening respiratory activity and reducing metabolic activity to reduce energy expenditure. Energy was produced by glycolysis and the tricarboxylic acid cycle for the synthesis of substances such as antibiotics. This study combined transcriptome and proteome sequencing data to provide a data reference for an in-depth study of the regulatory mechanism of salivary gland secretions of H. nipponia under starvation stress by analyzing DEGs and DEPs. [ABSTRACT FROM AUTHOR]

The lincoamide antibiotic lincomycin, derived from Streptomyces lincolnensis, is widely used for the treatment of infections caused by gram-positive bacteria. As a common global regulatory factor of GntR family, DasR usually exists as a regulatory factor that negatively regulates antibiotic synthesis in Streptomyces. However, the regulatory effect of DasR on lincomycin biosynthesis in S. lincolnensis has not been thoroughly investigated. The present study demonstrates that DasR functions as a positive regulator of lincomycin biosynthesis in S. lincolnensis, and its overexpression strain OdasR exhibits a remarkable 7.97-fold increase in lincomycin production compared to the wild-type strain. The effects of DasR overexpression could be attenuated by the addition of GlcNAc in the medium in S. lincolnensis. Combined with transcriptome sequencing and RT-qPCR results, it was found that most structural genes in GlcNAc metabolism and central carbon metabolism were up-regulated, but the lincomycin biosynthetic gene cluster (lmb) were down-regulated after dasR knock-out. However, DasR binding were detected with the DasR responsive elements (dre) of genes involved in GlcNAc metabolism pathway through electrophoretic mobility shift assay, while they were not observed in the lmb. These findings will provide novel insights for the genetic manipulation of S. lincolnensis to enhance lincomycin production. Key points: • DasR is a positive regulator that promotes lincomycin synthesis and does not affect spore production • DasR promotes lincomycin production through indirect regulation • DasR correlates with nutrient perception in S. lincolnensis [ABSTRACT FROM AUTHOR]

Background: Optically active D-amino acids are widely used as intermediates in the synthesis of antibiotics, insecticides, and peptide hormones. Currently, the two-enzyme cascade reaction is the most efficient way to produce D-amino acids using enzymes DHdt and DCase, but DCase is susceptible to heat inactivation. Here, to enhance the enzymatic activity and thermal stability of DCase, a rational design software "Feitian" was developed based on kcat prediction using the deep learning approach. Results: According to empirical design and prediction of "Feitian" software, six single-point mutants with high kcat value were selected and successfully constructed by site-directed mutagenesis. Out of six, three mutants (Q4C, T212S, and A302C) showed higher enzymatic activity than the wild-type. Furthermore, the combined triple-point mutant DCase-M3 (Q4C/T212S/A302C) exhibited a 4.25-fold increase in activity (29.77 ± 4.52 U) and a 2.25-fold increase in thermal stability as compared to the wild-type, respectively. Through the whole-cell reaction, the high titer of D-HPG (2.57 ± 0.43 mM) was produced by the mutant Q4C/T212S/A302C, which was about 2.04-fold of the wild-type. Molecular dynamics simulation results showed that DCase-M3 significantly enhances the rigidity of the catalytic site and thus increases the activity of DCase-M3. Conclusions: In this study, an efficient rational design software "Feitian" was successfully developed with a prediction accuracy of about 50% in enzymatic activity. A triple-point mutant DCase-M3 (Q4C/T212S/A302C) with enhanced enzymatic activity and thermostability was successfully obtained, which could be applied to the development of a fully enzymatic process for the industrial production of D-HPG. [ABSTRACT FROM AUTHOR]

The processes of biocatalytic synthesis of cefamandole and cefazoline, as well as four "chimeric" cephalosporins carrying functional groups of these antibiotics in the C3 or C7 position of β-lactam, were carried out using immobilized cephalosporin-acid synthetase under mild standard conditions. A higher efficiency of biocatalytic acylation of β-lactams with a 1(H)-tetrazolylacetic acid residue was demonstrated compared to acylation with mandelic acid residue. The chemical structure of the obtained compounds was confirmed using the HPLC-MS method. The possibility of using directly reaction mixtures for evaluating the antibacterial activity of the compounds synthesized without isolating the target products is demonstrated. The activity of the obtained cephalosporins against twelve microorganisms belonging to the genera Enterococcus, Acinetobacter, Serratia, Pseudomonas, Staphylococcus, and Escherichia was evaluated by the method of diffusion into agar. The activity of synthesized "chimeric" cephalosporins against four microorganisms was found: Escherichia coli VKPM B-6695, Staphylococcus aureus VKPM B-6646, Staphylococcus aureus VKPM B‑8171, and Staphylococcus epidermidis VKPM B-12635. [ABSTRACT FROM AUTHOR]

Background and Objective: Managing drug-food interactions is essential for optimizing the effectiveness and safety profile of quinolones. Following PRISMA guidelines, we systematically reviewed the influence of dietary interventions on the bioavailability of 22 quinolones. Methods: All studies describing or investigating the impact of food, beverages, antacids, and mineral supplements on pharmacokinetic parameters or pharmacokinetic/pharmacodynamic indices of orally taken quinolones were considered for inclusion. We excluded reviews, in vitro and in silico studies, studies performed on animals, and those involving alcohol. We performed the search in Medline (via PubMed), Embase, and Cochrane Library, covering reports from database inception to December 2022. We used the following tools to assess the risk of bias: version 2 of the Cochrane risk-of-bias tool for parallel trials, the Cochrane risk-of-bias tool for cross-over studies, and the NIH quality assessment tool for before-after studies. We performed quantitative analyses for each quinolone if two or more food-effect studies with specified and comparable study designs were available. If meta-analyses were not applicable, we qualitatively summarized the results. Results: We included 109 studies from 101 reports. Meta-analyses were conducted for 12 antibiotics and qualitative synthesis was employed for the remaining drugs. Of the studies, 60.5% were open-label, cross-over, as recommended by FDA. We judged 46% of studies as having a high risk of bias and only 4% of having a low risk of bias. Among 19 quinolones with available food impact data, 14 (74%) had potentially clinically important interactions. For nalidixic acid, oxolinic acid, and tosufloxacin, food exerted a high positive impact on bioavailability (AUC or Cmax increased by > 45%), whereas, for all the remaining drugs, postprandial absorption was lower. The most significant negative influence of food (AUC or Cmax decreased by > 40%) occurred for delafloxacin capsules and norfloxacin, whereas the moderate influence (AUC or Cmax decreased by 30–40%) occurred for nemonoxacin and rufloxacin. All 14 analysed quinolones showed a substantial reduction in bioavailability when co-administered with antacids and mineral supplements, except for calcium preparations. The impact of beverages was evaluated for 10 quinolones, with 50% experiencing significantly reduced absorption in the presence of milk (the highest negative impact for ciprofloxacin). Moreover, both ciprofloxacin and levofloxacin demonstrated compromised bioavailability when consumed with orange juice, particularly calcium-fortified. Discussion: Several factors may influence interactions, including the physicochemical characteristics of quinolones, the type of intervention, drug formulation, and the patient's health status. We assessed the quality of evidence as low due to the poor actuality of included studies, their methodological diversity, and uneven data availability for individual drugs. [ABSTRACT FROM AUTHOR]

Root rot caused by Fusarium spp. is the most destructive disease on Atractylodes lancea, one of the large bulks and most common traditional herbal plants in China. In this study, we isolated a bacterial strain, CF3, from the rhizosphere soil of A. lancea and determined its inhibitory effects on F. oxysporum in both in vitro and in vivo conditions. To deeply explore the biocontrol potential of CF3, we sequenced the whole genome and investigated the key pathways for the biosynthesis of many antibiotic compounds. The results revealed that CF3 is a member of Burkholderia ambifaria, harboring two chromosomes and one plasmid as other strains in this species. Five antibiotic compounds were found that could be synthesized due to the existence of the bio-synthesis pathways in the genome. Furthermore, the synthesis of antibiotic compounds should be confirmed by in vitro experiments and novel compounds should be purified and characterized in further studies. [ABSTRACT FROM AUTHOR]

This article discusses the molecular mechanisms of bacterial communication and their role in biocontrol. Bacteria are social organisms that engage in cooperative and competitive interactions, which are crucial for their survival. These interactions are supported by bacterial communication, which involves the exchange of signals between cells. Signals can be diverse, but they are generally small diffusible molecules that cross cell membranes and freely diffuse through the environment. Bacteria use communication systems to evaluate their density and synchronize their behavior, such as in biofilm formation. However, communication can be disrupted by other organisms, and strategies to quench bacterial communication are being developed for biocontrol purposes. [Extracted from the article]

Molecular biological techniques and bioinformatic analysis were used to investigate the phylogenetic and functional diversity of the prokaryotic complex of soil microcosms. The dominant organisms of the hydrolytic community were different in the samples from different climatic zones. In the soils subject to anthropogenic or abiogenic load, apart from decreased diversity and abundance of prokaryotes, the number of the genes marking the ability to degrade xenobiotics, as well as those encoding nitrogen conversion and metabolism of vitamins and cofactors, was found to increase. Under heavy oil contamination, the bacterial community was capable of nitrification; its role increased in the lower horizons of the soil profile. The patterns revealed in the work indicate high metabolic potential of the prokaryotic component of the studied soils. [ABSTRACT FROM AUTHOR]

Soil and rhizosphere bacteria act as a rich source of secondary metabolites, effectively fighting against a diverse array of pathogens. Certain Pseudomonas species harbor biosynthetic gene clusters for producing both pyoluteorin and 2,4-diacetylphloroglucinol (2,4-DAPG), which are polyketides that exhibit highly similar antimicrobial spectrum against bacteria and fungi or oomycete. A complex cross talk exists between pyoluteorin and 2,4-DAPG biosynthesis, and production of 2,4-DAPG was strongly repressed by pyoluteorin, yet the underlying mechanism is still elusive. In this study, we find that the TetR family transcription factor PhlH is involved in the cross talk between pyoluteorin and 2,4-DAPG biosynthesis. PhlH binds to a palindromic sequence within the promoter of phlG (PphlG), which encodes a C-C bond hydrolase responsible for degrading 2,4-DAPG. As a signaling molecule, pyoluteorin disrupts the PhlH-PphlG complex by binding to PhlH, leading to decreased levels of 2,4-DAPG. Proteomics data suggest that pyoluteorin regulates multiple physiological processes including fatty acid biosynthesis and transportation of taurine, siderophore, and amino acids. Our work not only reveals a novel mechanism of cross talk between pyoluteorin and 2,4-DAPG biosynthesis, but also highlights pyoluteorin's role as a messenger in the complex communication network of Pseudomonas. IMPORTANCE Antibiosis serves as a crucial defense mechanism for microbes against invasive bacteria and resource competition. These bacteria typically orchestrate the production of multiple antibiotics in a coordinated fashion, wherein the synthesis of one antibiotic inhibits the generation of another. This strategic coordination allows the bacterium to focus its resources on producing the most advantageous antibiotic under specific circumstances. However, the underlying mechanisms of distinct antibiotic production in bacterial cells remain largely elusive. In this study, we reveal that the TetR family transcription factor PhlH detects the secondary metabolite pyoluteorin and mediates the cross talk between pyoluteorin and 2,4-DAPG biosynthesis in the biocontrol strain Pseudomonas protegens Pf-5. These findings hold promise for future research, potentially informing the manipulation of these systems to enhance the effectiveness of biocontrol agents. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) promotes research aimed at developing new drugs from natural compounds. Fungi are important producers of bioactive molecules, and they are often effective against other fungi and/or bacteria and are thus a potential source of new antibiotics. Basidiomycota crude extracts, which have previously been proven to be active against Pseudomonas aeruginosa ATCC27853, were subjected to liquid chromatographic separation by RP-18, leading to six macro-fractions for each fungal extract. The various fractions were tested for their bioactivities against P. aeruginosa ATCC27853, and ten of them were characterized by HPLC-HRMS and NMR. Further chromatographic separations were performed for a few selected macro-fractions, yielding seven pure compounds. Bioactivity was mainly found in the lipophilic fractions containing fatty acids and their derivatives, such as hydroxy or keto C-18 unsaturated acids, and in various complex lipids, such as glycolipids and related compounds. More hydrophilic molecules, such as GABA, phenethylamine, two chromogenic anthraquinoids and pistillarin, were also isolated, and their antibacterial activities were recorded. The novelties of this research are as follows: (i) the genera Cortinarius and Mycena have never been investigated before for the synthesis of antibiotic compounds; (ii) the molecules produced by these genera are known, but their production has never been reported in the investigated fungi; (iii) the determination of bacterial siderophore synthesis inhibition by certain compounds from Cortinarius and Mycena. [ABSTRACT FROM AUTHOR]

The article focuses on the significant role of Actinobacteria, particularly Streptomyces species, in producing a wide range of antibiotics, anticancer agents, and agrochemicals. Topics include the ongoing exploration of natural products from actinomycetes through microbial genomics and synthetic biology, the insights gained into biosynthesis and industrial yield improvement, and the potential for these microorganisms to inspire the development of next-generation medicines.

Dickeya solani, belonging to the Soft Rot Pectobacteriaceae, are aggressive necrotrophs, exhibiting both a wide geographic distribution and a wide host range that includes many angiosperm orders, both dicot and monocot plants, cultivated under all climatic conditions. Little is known about the infection strategies D. solani employs to infect hosts other than potato (Solanum tuberosum L.). Our earlier study identified D. solani Tn5 mutants induced exclusively by the presence of the weed host S. dulcamara. The current study assessed the identity and virulence contribution of the selected genes mutated by the Tn5 insertions and induced by the presence of S. dulcamara. These genes encode proteins with functions linked to polyketide antibiotics and polysaccharide synthesis, membrane transport, stress response, and sugar and amino acid metabolism. Eight of these genes, encoding UvrY (GacA), tRNA guanosine transglycosylase Tgt, LPS-related WbeA, capsular biosynthesis protein VpsM, DltB alanine export protein, glycosyltransferase, putative transcription regulator YheO/PAS domain-containing protein, and a hypothetical protein, were required for virulence on S. dulcamara plants. The implications of D. solani interaction with a weed host, S. dulcamara, are discussed. [ABSTRACT FROM AUTHOR]

This article discusses the challenges of developing new antibiotics, particularly for the gram-negative bacteria Pseudomonas aeruginosa. The lack of therapeutic options for this bacteria is concerning, as it is classified as a "serious threat" by the CDC and has high rates of antibiotic resistance. The article presents permeation guidelines for P. aeruginosa, which can help in designing small molecules that can effectively penetrate the bacteria and gain intracellular access. These guidelines differ from those for another gram-negative bacteria, Escherichia coli, and provide insights into the physiological differences between the two bacteria. The article suggests that these permeation guidelines can aid in the development of new antibiotics by enhancing the accumulation of candidate drugs. [Extracted from the article]

Bees represent not only a valuable asset in agriculture, but also serve as a model organism within contemporary microbiology. The metagenomic composition of the bee superorganism has been substantially characterized. Nevertheless, traditional cultural methods served as the approach to studying brood combs in the past. Indeed, the comb microbiome may contribute to determining larval caste differentiation and hive immunity. To further this understanding, we conducted a shotgun sequencing analysis of the brood comb microbiome. While we found certain similarities regarding species diversity, it exhibits significant differentiation from all previously described hive metagenomes. Many microbiome members maintain a relatively constant ratio, yet taxa with the highest abundance level tend to be ephemeral. More than 90% of classified metagenomes were Gammaproteobacteria, Bacilli and Actinobacteria genetic signatures. Jaccard dissimilarity between samples based on bacteria genus classifications hesitate from 0.63 to 0.77, which for shotgun sequencing indicates a high consistency in bacterial composition. Concurrently, we identified antagonistic relationships between certain bacterial clusters. The presence of genes related to antibiotic synthesis and antibiotic resistance suggests potential mechanisms underlying the stability of comb microbiomes. Differences between pupal and larval combs emerge in the total metagenome, while taxa with the highest abundance remained consistent. All this suggests that a key role in the functioning of the comb microbiome is played by minor biodiversity, the function of which remains to be established experimentally. [ABSTRACT FROM AUTHOR]

(R)-(-)-mandelic acid is an important carboxylic acid known for its numerous potential applications in the pharmaceutical industry as it is an ideal starting material for the synthesis of antibiotics, antiobesity drugs and antitumor agents. In past few decades, the synthesis of (R)-(-)-mandelic acid has been undertaken mainly through the chemical route. However, chemical synthesis of optically pure (R)-(-)-mandelic acid is difficult to achieve at an industrial scale. Therefore, its microbe mediated production has gained considerable attention as it exhibits many merits over the chemical approaches. The present review focuses on various biotechnological strategies for the production of (R)-(-)-mandelic acid through microbial biotransformation and enzymatic catalysis; in particular, an analysis and comparison of the synthetic methods and different enzymes. The wild type as well as recombinant microbial strains for the production of (R)-(-)-mandelic acid have been elucidated. In addition, different microbial strategies used for maximum bioconversion of mandelonitrile into (R)-(-)-mandelic acid are discussed in detail with regard to higher substrate tolerance and maximum bioconversion. Mandelonitrile, mandelamide and o-chloromandelonitrile can be used as substrates to produce (R)-(-)-mandelic acid by enzymes. Three enzymes (nitrilase, nitrile hydratase and amidase) are systematically introduced for production of (R)-(-)-mandelic acid. Microbial transformation is able to produce optically pure (R)-(-)-mandelic acid with 100% productive yield. [ABSTRACT FROM AUTHOR]

The efficiency has been compared of the optimized acylation processes of 7-aminocephalosporanic acid (7-ACA) and its С3 derivatives (7-amino-3-[2-methyl-1,3,4-thiadiazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid (TDA), and 1-methyl-5-mercapto-1,2,3,4-tetrazolyl-7-aminocephalosporanic acid (7-TMCA)) by methyl esters of 1(H)-terazolylacetic and D-mandelic acids (METzAA and MEMA). These processes are catalyzed by immobilized cephalosporin-acid synthetase (IECASA) and are the biocatalytic stages of two different chemical-biocatalytic pathways for the synthesis of cefazolin (CEZ) and cefamandole (CFM). Biocatalytic acylation of 7-ACA resulting in the formation of semi-products of the synthesis of antibiotics proceeded more efficiently than acylation of the corresponding C3 derivatives of 7-ACA, leading to the formation of CEZ and CFM, in terms of both the achieved product yield and the possibility of obtaining compounds in high concentration in the reaction mixture. At the same time, the synthetase ability of IECASA is highest in the acylation of 7-ACA using METzAA. It was shown that the chemical-biocatalytic synthesis of CEZ and CFM by direct biocatalytic acylation of 7-ACA followed by chemical modification of the semi-product at the C3 position of the β-lactam nucleus is a promising alternative to the traditional pathway using the biocatalytic acylation of 7-ACA derivatives with a substituted 3-acetoxy group. [ABSTRACT FROM AUTHOR]

Drug resistance has limited the synthesis of new antibiotics. Therefore, the use of compounds that do not have drug resistance has been considered. Antimicrobial peptides are among the compounds for which drug resistance has not been reported. On the other hand, it has been found that the activity of these compounds is less than that of antibiotics. Therefore, the design of appropriate antimicrobial peptides is challenging. To address this challenge, efforts have been made to understand their mechanism of action. However, their mechanism of action is not well understood. In this work, the interaction of two cyclic and linear antimicrobial peptides with sodium dodecyl sulfate micelles as cell membrane mimetics method has been studied by molecular dynamics simulation. The micellar radius of gyration shows good agreement with the experimental results and the results of other simulations performed. Calculation of the conformational factor shows that cyclic antimicrobial peptide has a greater affinity for interaction with micelles. Charged and aromatic residues are involved in the interaction of cyclic antimicrobial peptides with micelles. Whereas, only charged residues are effective in the interaction of the linear antimicrobial peptides with micelle. [ABSTRACT FROM AUTHOR]

The MCM-41 adsorbent was derived from Iranian natural pumice as source of silica for the first time and highly grafted with APTES for anchoring cephalexin (CEX) molecules. The parent MCM-41 had a specific surface of 913 m2/g while the value decreased to 819 m2/g after grafting with 6.52 μmol APTES per square meter of adsorbent surface. Batch adsorption data were best fitted onto various kinetic and isotherm model with higher correlation coefficient and lower residual sum of squares for pseudo-first-order kinetic model and Langmuir isotherm model. In this regard, amine-grafted MCM-41 (N-MCM-41) showed an excellent adsorption capacity of 56.31 mg/g according to Langmuir model. Removal efficiency was decreased by 50% in the presence of coexisting ions. Nonlinear Thomas model best fitted onto breakthrough curves at various experimental condition. For synthetic solution and at moderate condition, about 41.53 mg/g of CEX was adsorbed in continues experiment. For simulated samples, 19.74 mg/g adsorption capacity was achieved under dynamic condition. Thermal destruction method was used to recover the spent adsorbent and after six cycle adsorption–desorption, adsorption capacity decreased from 41.53 to 8.72 mg/g. Overall, the present study proposed N-MCM-41 prepared from natural pumice for effective adsorption–desorption of CEX, which could be a guidance for antibiotics adsorption. [ABSTRACT FROM AUTHOR]

Abstract—Low molecular-weight thiols as glutathione and cysteine are an important part of the cell's redox regulation system. Previously, we have shown that inactivation of ADP-heptose synthesis in Escherichiacoli with a gmhA deletion induces the oxidative stress. It is accompanied by rearrangement of thiol homeostasis and increased sensitivity to antibiotics. In our study, we found that restriction of cysteine metabolism (∆cysB and ∆cysE) and inhibition of glutathione synthesis (∆gshAB) lead to a decrease in the sensitivity of the ∆gmhA mutant to antibiotics but not to its expected increase. At the same time, blocking of the export of cysteine (∆eamA) or increasing import (Ptet-tcyP) into cells of the oxidized form of cysteine–cystine leads to an even greater increase in the sensitivity of gmhA-deleted cells to antibiotics. In addition, there is no correlation between the cytotoxic effect of antibiotics and the level of reactive oxygen species (ROS), the total pool of thiols, or the viability of the initial cell population. However, a correlation between the sensitivity to antibiotics and the level of oxidized glutathione in cells was found in our study. Apparently, a decrease in the content of low-molecular-weight thiols saves NADPH equivalents and limits the processes of protein redox modification. This leads to increasing of resistance of the ∆gmhA strain to antibiotics. An increase in low-molecular-weight thiols levels requires a greater expenditure of cell resources, leads to an increase in oxidized glutathione and induces to greater increase in sensitivity of the ∆gmhA strain to antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: Bacillus licheniformis (B. licheniformis) is a microorganism with a wide range of probiotic properties and applications. Isolation and identification of novel strains is a major aspect of microbial research. Besides, different carbon sources have varying effects on B. licheniformis in regulating the microenvironment, and these mechanisms need to be investigated further. Methods: In this study, we isolated and identified a new strain of B. licheniformis from bovine rumen fluid and named it B. licheniformis NXU98. The strain was treated with two distinct carbon sources--microcrystalline cellulose (MC) and cellobiose (CB). A combination of transcriptome and proteome analyses was used to investigate different carbon source effects. Results: The results showed that B. licheniformis NXU98 ABC transporter proteins, antibiotic synthesis, flagellar assembly, cellulase-related pathways, and proteins were significantly upregulated in the MC treatment compared to the CB treatment, and lactate metabolism was inhibited. In addition, we used MC as a distinct carbon source to enhance the antibacterial ability of B. licheniformis NXU98, to improve its disease resistance, and to regulate the rumen microenvironment. Discussion: Our research provides a potential new probiotic for feed research and a theoretical basis for investigating the mechanisms by which bacteria respond to different carbon sources. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of the broad‐spectrum antibiotic (1R,2R)‐chloramphenicol and its congener is described here. Our approach is based on the Evans asymmetric aldol reaction, which involves the use of a chiral 'glycine enolate equivalent' derived from N‐(N‐Boc‐glycinyl) oxazolidinone and p‐nitrobenzaldehyde. The reaction is catalyzed by TiCl4 and Hunig's base DIPEA, resulting in the production of both Evans syn‐ and non‐Evans anti‐adducts in a 3 : 1 diastereomeric ratio with 85 % combined yield. We achieved diastereoselectivity control in the reaction using Lewis acid TiCl4 along with DIPEA. Subsequently, the syn‐ and anti‐aldol products were transformed into (1R,2R)‐ and (1R,2S)‐chloramphenicol, respectively, using a three‐step method. The stereochemistry of the clinically used chloramphenicol was confirmed by measuring the optical rotation of the final compounds. [ABSTRACT FROM AUTHOR]

Simple Summary: The lower termite Coptotermes gestroi is widely distributed in Northern Vietnam and is an important urban pest that destroys wooden constructions such as pagodas, temples, and furniture. Although the metagenomic DNA of prokaryotes freely living in the termite gut has been sequenced and analyzed, the overall picture of the prokaryotic diversity, including archaea and their function, has not been investigated. The present study, for the first time, revealed the differences in the structure and function of free-living prokaryotes in the termite gut. The bacterial community was formed and adapted to aid the hosts' survival and development even in the presence of pesticides. Beyond the potential function of the bacteria towards lignocellulose digestion, free-living bacteria and archaea also harbor diverse genes coding for the enzymes/proteins involved in reductive acetogenesis, methanogenesis, methane and sulfur metabolism, and nitrogen fixation and recycling to supply energy for the host; the synthesis of antibiotics for host defense; and the detoxification of aromatic compounds. The present study provides a valuable scientific basis for the mining of novel bacterial genes and the isolation of bacteria from the termite gut for agricultural, environmental, pharmaceutical, and medical applications. Termites' digestive systems, particularly in lower termites with the presence of protozoa, are unique ecological niches that shelter a diverse microbiota with a variety of functions for the host and the environment. In 2012, the metagenomic DNA (5.4 Gb) of the prokaryotes that freely live in the gut of the lower termite Coptotermes gestroi were sequenced. A total of 125,431 genes were predicted and analyzed in order to mine lignocellulolytic genes. however, the overall picture of the structure, diversity, and function of the prokaryotic gut microbiota was not investigated. In the present study, these 125,431 genes were taxonomically classified by MEGAN and functionally annotated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and by the Carbohydrate-Active enZYmes (CAZy) and HMMER databases. As a result, 95,751 bacterial genes were classified into 35 phyla. The structure of the bacteria, typified by a high ratio of Firmicutes to Bacterioidetes, was distinct from the structure of the entirety of the bacteria in the lower or higher termites' guts. The archaea (533 genes) were distributed into 4 phyla, 10 classes, 15 orders, 21 families, 47 genera, and 61 species. Although freely living in the guts, the prokaryotic community was formed, developed, and adapted to exhibit unique interactions in order to perform mutual roles of benefit to their hosts. Methanobacteriales, accounting for 61% of the archaea symbionts, seem to play an important role in methanogenesis. Concomitantly, bacterial methanotrophs in the gut utilize methane and combine with other bacterial groups, including potential lignocellulolytic degraders, acetogens, sulfur bacteria, and nitrogen-recycling bacteria, to efficiently convert wood with little nitrogen into acetates via certain pathway modules specified by prokaryotes that freely live in the gut. This forms an important energy source for the termites. Furthermore, bacteria carry 2223 genes involved in the biosynthesis of 17 antibiotic groups. The gut bacteria also possess genes for the degradation of 18 toxic aromatic compounds, of which four are commercial pesticides against termites commonly used for the preservation of wooden constructions. Eight of the eighteen pathways were the first to be reported from the termite gut. Overall, this study sheds light on the roles of the freely living bacteria and archaea in the C. gestroi gut, providing evidence that the gut microbiome acts as the second host genome, contributing both nutrients and immunity to support the host's existence, growth, and development. [ABSTRACT FROM AUTHOR]

Actinobacteria are prevalent in the rhizosphere and phyllosphere of diverse plant species where they help to enhance tolerance of plants against biotic and abiotic stresses. Here, we show that the plant hormones jasmonic acid (JA) and methyl jasmonate (MeJA) affect the growth, development, and specialized metabolism of Streptomyces. Exposure of Streptomyces coelicolor to JA or MeJA led to enhanced production of the polyketide antibiotic actinorhodin. JA also exhibited toxicity toward Streptomyces and Streptacidiphilus at higher concentrations, whereby streptomycetes were more tolerant to JA than members of the genus Streptacidiphilus. Tolerance to JA could be linked to its conjugation by the bacteria with glutamine. Additionally, JA conjugates with valine, tyrosine, phenylalanine, and leucine/isoleucine were identified. In contrast to JA, synthetic JA conjugates failed to activate antibiotic production and showed significantly reduced toxicity. Thus, our findings provide insights into a previously unknown defense mechanism deployed by Streptomycetaceae to a plant hormone. The underlying mechanism encompasses the attachment of amino acids to JA, which in turn safeguards the bacteria against the harmful impacts of the plant hormone. This study adds to the growing body of evidence that plant hormones can have a significant impact on members of the plant microbiome by affecting their growth, development, and secondary metabolism. IMPORTANCE Microorganisms that live on or inside plants can influence plant growth and health. Among the plant-associated bacteria, streptomycetes play an important role in defense against plant diseases, but the underlying mechanisms are not well understood. Here, we demonstrate that the plant hormones jasmonic acid (JA) and methyl jasmonate directly affect the life cycle of streptomycetes by modulating antibiotic synthesis and promoting faster development. Moreover, the plant hormones specifically stimulate the synthesis of the polyketide antibiotic actinorhodin in Streptomyces coelicolor. JA is then modified in the cell by amino acid conjugation, thereby quenching toxicity. Collectively, these results provide new insight into the impact of a key plant hormone on diverse phenotypic responses of streptomycetes. [ABSTRACT FROM AUTHOR]

The usefulness of ketonization reactions for the valorization of a wide plethora of biomass-derived carboxylic acids is widely recognized; however, the full potential of this reaction has yet to be suitably exploited for the production of high added-value aromatic and/or aliphatic asymmetric ketones. For this reason, herein we report for the first time in the literature the continuous-flow, gas-phase synthesis of 2-acetyl furan (AF) by means of the catalytic cross-ketonization of bio-based 2-methyl furoate (2-MF) and acetic acid (AA) over a simple and cheap ZrO2 catalyst. Interestingly, AF is considered a valuable food additive and a pharmaceutical intermediate for the synthesis of antibiotics. The optimization of the molar ratio between reactants at 350 °C allowed us to achieve 87% AF selectivity at 90% 2-MF conversion, with a space–time yield of 0.152 h−1, a value that is similar to the ones obtained by following the traditional Friedel–Crafts acylation and Wacker oxidation routes. On the other hand, the E-factor of the herein-proposed process is several times lower compared to the aforementioned traditional routes performed in the liquid phase and under batch conditions. Finally, the versatility of the cross-ketonization synthetic approach was successfully demonstrated and applied for the selective synthesis of other valuable acyl furans (i.e., propionyl furan and butyryl furan). [ABSTRACT FROM AUTHOR]

Fruits harbour abundant and diverse microbial communities that protect them from post‐harvest pathogens. Identification of functional traits associated with a given microbiota can provide a better understanding of their potential influence. Here, we focused on the epiphytic microbiome of apple fruit. We suggest that shotgun metagenomic data can indicate specific functions carried out by different groups and provide information on their potential impact. Samples were collected from the surface of 'Golden Delicious' apples from four orchards that differ in their geographic location and management practice. Approximately 1 million metagenes were predicted based on a high‐quality assembly. Functional profiling of the microbiome of fruits from orchards differing in their management practice revealed a functional shift in the microbiota. The organic orchard microbiome was enriched in pathways involved in plant defence activities; the conventional orchard microbiome was enriched in pathways related to the synthesis of antibiotics. The functional significance of the variations was explored using microbial network modelling algorithms to reveal the metabolic role of specific phylogenetic groups. The analysis identified several associations supported by other published studies. For example, the analysis revealed the nutritional dependencies of the Capnodiales group, including the Alternaria pathogen, on aromatic compounds. [ABSTRACT FROM AUTHOR]

Yersinia enterocolitica is a harmful bacterium transmitted through contaminated food, causing gastrointestinal illness and lymph node inflammation. The rise of drug-resistant strains of Y. enterocolitica poses a serious public health threat, necessitating research on its ecology, related species, and unique genes linked to virulence and antibiotic resistance. This study identified eight microorganisms similar to Y. enterocolitica and conducted a pan-genomic analysis, revealing specific genes exclusive to Y. enterocolitica. Enrichment analysis of these genes unveiled their involvement in antibiotic synthesis pathways, such as siderophore production, osmoregulated periplasmic glucan activation, and antibiotic resistance. These pathways, including biofilm formation and increased antibiotic tolerance, are vital for Yersinia's virulence. Furthermore, specific genes related to glutamate metabolism, nitrogen regulation, motility, purine, and pyrimidine synthesis may contribute to Y. enterocolitica's pathogenicity, growth, and virulence factor production. Phylogenetic analysis demonstrated the evolutionary relationship between Y. enterocolitica and similar species like Escherichia coli, Campylobacter jejuni, and Salmonella enterica, stressing the need to monitor Y. enterocolitica in slaughterhouses due to animal carriers. The study's findings shed light on the ecological factors and genetic mechanisms driving Y. enterocolitica's pathogenicity and antibiotic resistance. Targeting genes involved in purine and pyrimidine synthesis, such as ushA, cpdB, and deoB, could be potential strategies for controlling pathogenicity and antimicrobial resistance. Understanding the relationships and genetic interactions between Y. enterocolitica and related microorganisms is crucial for developing effective surveillance and management approaches in the future. [ABSTRACT FROM AUTHOR]

Despite the advances in understanding the regulatory networks for secondary metabolite production in Streptomyces, the participation of the two-component systems (TCS) in this process still requires better characterization. These sensing systems and their responses to environmental stimuli have been described by evaluating mutant strains with techniques that allow in-depth regulatory responses. However, defining the stimulus that triggers their activation is still a task. The transmembrane nature of the sensor kinases and the high content of GC in the streptomycetes represent significant challenges in their study. In some examples, adding elements to the assay medium has determined the respective ligand. However, a complete TCS description and characterization requires specific amounts of the involved proteins that are most difficult to obtain. The availability of enough sensor histidine kinase concentrations could facilitate the identification of the ligand–protein interaction, and besides would allow the establishment of its phosphorylation mechanisms and determine their tridimensional structure. Similarly, the advances in the development of bioinformatics tools and novel experimental techniques also promise to accelerate the TCSs description and provide knowledge on their participation in the regulation processes of secondary metabolite formation. This review aims to summarize the recent advances in the study of TCSs involved in antibiotic biosynthesis and to discuss alternatives to continue their characterization. Key points: • TCSs are the environmental signal transducers more abundant in nature. • The Streptomyces have some of the highest number of TCSs found in bacteria. • The study of signal transduction between SHKs and RRs domains is a big challenge. [ABSTRACT FROM AUTHOR]

Inhibition of bacterial cell wall synthesis by antibiotics such as β-lactams is thought to cause explosive lysis through loss of cell wall integrity. However, recent studies on a wide range of bacteria have suggested that these antibiotics also perturb central carbon metabolism, contributing to death via oxidative damage. Here, we genetically dissect this connection in Bacillus subtilis perturbed for cell wall synthesis, and identify key enzymatic steps in upstream and downstream pathways that stimulate the generation of reactive oxygen species through cellular respiration. Our results also reveal the critical role of iron homeostasis for the oxidative damage-mediated lethal effects. We show that protection of cells from oxygen radicals via a recently discovered siderophore-like compound uncouples changes in cell morphology normally associated with cell death, from lysis as usually judged by a phase pale microscopic appearance. Phase paling appears to be closely associated with lipid peroxidation. Inhibition of bacterial cell wall synthesis by β-lactam antibiotics results in a loss of cell wall integrity, but cells die via a combination of downstream events involving metabolic perturbations and oxidative damage. Here, Kawai et al. identify key enzymatic steps that stimulate the generation of reactive oxygen species and highlight the role of iron homeostasis in the lethal effects mediated by oxidative damage. [ABSTRACT FROM AUTHOR]

Objective. The objective of this study was to assess the results of a clinical guideline for the treatment and early discharge of patients with complicated acute appendicitis in terms of infectious complications and hospital stay. Materials and methods. A guideline for appendicitis treatment according to severity was created. Complicated appendicitis cases were treated with ceftriaxone-metronidazole for 48h, with discharge being approved if certain clinical and blood test criteria were met. A retrospective analytical study comparing the incidence of postoperative intra-abdominal abscess (IAA) and surgical site infection (SSI) in patients under 14 years of age to whom the new guideline was applied (Group A) vs. the historical cohort (Group B, treated with gentamicin-metronidazole for 5 days) was carried out. A prospective cohort study to assess which antibiotic therapy (amoxicillin-clavulanic acid or cefuroxime-metronidazole) proved more effective in patients meeting early discharge criteria was also conducted. Results. 205 patients under 14 years of age were included in Group A, whereas 109 patients were included in Group B. IAA was present in 14.3% of patients from Group A vs. 13.8% from Group B (p= 0.83), while SSI was present in 1.9% of patients from Group A vs. 8.25% from Group B (p= 0.008). Early discharge criteria were met by 62.7% of patients from Group A. Median hospital stay decreased from 6 to 3 days. At discharge, 57% of patients received amoxicillin-clavulanic acid, whereas 43% received cefuroxime-metronidazole, with no differences being found in terms of SSI (p= 0.24) or IAA (p= 0.12). Conclusions. Early discharge reduces hospital stay without increasing the risk of postoperative infectious complications. Amoxicillin-clavulanic acid is a safe option for at-home oral antibiotic therapy. [ABSTRACT FROM AUTHOR]

Thuringiensin is a thermostable nucleoside metabolite produced by Bacillus thuringiensis and has insecticidal activity against various pests. The synthesis cluster of thuringiensin was cloned and the biosynthesis pathway deduced and clarified in a previous study. ThuE catalyzes phosphorylation from precursor C to thuringiensin in the final step of thuringiensin maturation. However, the transport mechanism of thuringiensin remains unclear. Here, we identify a novel predicted MFS transporter named ThuT (thuringiensin transporter) which is necessary for the biosynthesis and secretion of thuringiensin. A thuT gene deletion resulted in a massive loss of thuringiensin in the extracellular space and a small accumulation in the intracellular space, implying its role in the transport of thuringiensin. The overall abundance of thuringiensin was significantly reduced, while the accumulation of precursor C in the thuT mutant suggests its role in thuringiensin biosynthesis. Further protein protein interaction analysis demonstrated that ThuT forms a complex with ThuE, which suggests the mechanism by which ThuT participates in thuringiensin maturation. We have identified the first transporter of thuringiensin and propose that the ThuT-ThuE complex could couple the maturation and transport of thuringiensin to avoid thuringiensin accumulation. A novel high-efficiency model coupling the synthesis and secretion of antibiotics has been revealed in B.thuringiensis. [Display omitted] • ThuT is a novel transporter involved in thuringiensin biosynthesis and secretion. • The thuT mutant accumulates thuringiensin inside but depletes it outside of cells. • ThuT forms a complex with thuringiensin maturation enzyme ThuE. • ThuT-ThuE complex couples thuringiensin maturation and transport. [ABSTRACT FROM AUTHOR]

Introduction: Pseudomonas fluorescens 2P24 was isolated from soil of natural decay associated with wheat take-all and it can effectively control soil-borne diseases caused by a variety of plant pathogens. 2,4-diacetylphloroglucinol (2,4-DAPG), is produced by P. fluorescens 2P24 and plays an important role in the prevention and control of plant diseases. To understand the resistant mechanism, in this study, we conducted experiments to explore the regulation role of rpoZ in the synthesis of the antibiotic 2,4-DAPG and regulation of QS system. Methods: A random mini-Tn5 mutagenesis procedure was used to screen regulators for phlA transcription in stain PM901, which containing a phlA::lacZ transcriptional fusion reporter plasmid. We identified 12 insertion mutants could significantly change phlA gene expression. By analyzing the amino acid sequences of the interrupted gene, we obtained a mutant strain Aa4-29 destroyed the rpoZ gene, which encodes the omiga subunit. We constructed the plasmid of rpoZ mutant (pBBR-ΔrpoZ) transformed into competent cells of P. fluorescens 2P24 by electro-transformation assay. The strains of P. fluorescens 2P24/pBBR, 2P24-ΔrpoZ/pBBR, 2P24-ΔrpoZ/pBBR-rpoZ were used to evaluate the regulation role of rpoZ in 2,4-DAPG production and quorum sensing system. Results: According to β-galactosidase activity, we found that rpoZ positively regulated the expression of phlA (a synthesis gene of 2,4-DAPG) and PcoI (a synthesis gene of PcoI/PcoR QS signal system) at the transcriptional level. The production of 2,4-DAPG antibiotic and signal molecule AHL was influenced by rpoZ. Further, rpoZ was involved in regulating rsmA expression. RpoZ also has a certain regulatory effect on rpoS transcription, but no effect on the transcription of phlF, emhABC and emhR. According to the biocontrol assay, P. fluorescens 2P24 strains with rpoZ showed obvious antagonism ability against the Rhizoctonia solani in cotton, while the mutant strain of rpoZ lost the biocontrol effect. RpoZ had a significant effect on the swimming and biofilm formation in P. fluorescens 2P24. Conclusion: Our data showed that rpoZ was an important regulator of QS system, 2,4-DAPG in P. fluorescens 2P24. This may imply that P. fluorescens 2P24 has evolved different regulatory features to adapt to different environmental threats. [ABSTRACT FROM AUTHOR]

Herein, we have designed for the fabrication of a series of g-C3N4/CuO composite by using one-step microwave-assisted synthesis for the degradation of antibiotics and detection of nano-molar range of toxic heavy metal ions. The synthesized g-C3N4/CuO composites were analyzed and characterized to know the structure, phase, surface area, absorption region, bandgap, and size of the composites. From the observation of TEM and XRD measurements, g-C3N4/CuO composites have hexagonal shape with average diameter of the particles is 25 ± 5 nm. The observed band gap values from UV-vis DRS for g-C3N4 nanosheets and CuO NPs are 2.64 eV and 1.72 eV. The synthesized g-C3N4/CuO composite has prodigious specific surface area (32.47 m2/g), which is the evident for superior heterogeneous catalytic applications. Therefore, the synthesized g-C3N4/CuO composites were tested for the degradation of antibiotics such as tetracycline (TC) and ciprofloxacin (CIP) under UV light illumination, it shows 88.02% and 90.01% degradation was observed within 1 h due to the matching optical band gap and internal charge transfer of excitons with in the heterojunction surface among g-C3N4 and CuO in the composite than the individual components (g-C3N4 and CuO) due to the high surface area and tiny particles of CuO were randomly deposited on the surface of g-C3N4 nanosheets. The catalytic reduction reaction follows as pseudo-first order equation and reused for 5 consecutive cycles without remarkable loss of catalytic activity. Moreover, the synthesized CuO NPs and g-C3N4/CuO composites were used as a prominent fluorescence sensing probe for the selective detection of Pb2+ in nano-molar range of concentration with Ksv is 1.38 × 104 mol− 1dm3. It was observed as a linear relationship based on the change in intensity, the limit of detection was determined to be 0.184 nM. [ABSTRACT FROM AUTHOR]

Streptomyces are soil dwelling bacteria that are notable for their ability to sporulate and to produce antibiotics and other secondary metabolites. Antibiotic biosynthesis is controlled by a variety of complex regulatory networks, involving activators, repressors, signaling molecules and other regulatory elements. One group of enzymes that affects antibiotic synthesis in Streptomyces is the ribonucleases. In this review, the function of five ribonucleases, RNase E, RNase J, polynucleotide phosphorylase, RNase III and oligoribonuclease, and their impact on antibiotic production will be discussed. Mechanisms for the effects of RNase action on antibiotic synthesis are proposed. [ABSTRACT FROM AUTHOR]

Bifidobacterium species are known for their ability to inhabit various habitats and are often regarded as the first colonisers of the human gut. In the present work, we have used comparative genomics to identify conserved genomic signatures specific to Bifidobacterium species associated with the human gut. Our approach discovered five genomic signatures with varying lengths and confidence. Among the predicted five signatures, a 1790 bp multi-drug resistance (MDR) signature was found to be remarkably specific to only those species that can colonise the human gut. The signature codes for a membrane transport protein belonging to the major facilitator superfamily (MFS) generally involved in MDR. Phylogenetic analyses of the MDR signature suggest a lineage-specific evolution of the MDR signature in bifidobacteria colonising the human gut. Functional annotation led to the discovery of two conserved domains in the protein; a catalytic MFS domain involved in the efflux of drugs and toxins, and a regulatory cystathionine-β-synthase (CBS) domain that can interact with adenosyl-carriers. Molecular docking simulation performed with the modelled tertiary structure of the MDR signature revealed the putative functional role of the covalently linked domains. The MFS domain displayed a high affinity towards various protein synthesis inhibitor antibiotics and human bile acids, whereas the C-terminally linked CBS domain exhibited favourable binding with molecular structures of ATP and AMP. Therefore, we believe that the predicted signature represents a niche-specific survival trait involved in bile and antibiotic resistance, imparting an adaptive advantage to the Bifidobacterium species colonising the human gut. [ABSTRACT FROM AUTHOR]

Antibiotic-impregnated bioactive therapeutic biomaterials are highly demanding due to the risk of infection associated with musculoskeletal injuries and bone replacement surgeries. In this study, we report the synthesis of antibiotic nanohybrid having an aqueous sensitive sheddable polycaprolactone (PCL) shell grafted over gentamicin sulphate (GS)-charged bioactive glass (BG) nanospheres via surface-initiated polymerization. This study indeed shows the additional role of GS, while its potential as an initiator for the ring opening polymerization of ε-caprolactone (CL) is investigated by choosing 1:0.175 and 1:0.53 weight ratio of CL:GS-loaded nanoparticles. The influence of monomer/initiator feed ratio on the synthesized PCL was evident in the unbound PCL fractions, suggesting the effective role of GS as an initiator. However, in the nanohybrids, the percentage grafting and shell thickness were comparable regardless of the quantity of drug-loaded particles used. The 1H NMR and MALDI-ToF analysis of the unbound PCL further confirmed the part of GS with the hydroxyl end group served as the surface anchoring group. The successful grafting of PCL was confirmed by different characterization techniques. The effective shedding of the shell in the aqueous environment and the subsequent release of GS were confirmed by the TEM analysis and zeta potential measurements. Additionally, the drug release was modulated with controlled burst release with only 15 wt% and 14 wt% release in the nanohybrids in the first 8 h, while it is 29 wt% for the unmodified BG nanoparticles. Studies of growth inhibition of clinically relevant strains such as E.coli, S.aureus, P.aeruginosa and B.subtilis indicated that the GS released from the nanohybrid retained antibacterial activity. Thus the GS-initiated polyester functionalization of drug-loaded BG nanoparticles, which enables an environment responsive as well as modulated release, is considered beneficial for further progresses in drug-loaded scaffolds. [ABSTRACT FROM AUTHOR]

Amphibians defend against pathogens using skin microbial communities, in addition to innate and adaptive immunity. Despite skin microbial communities play a key role in the immune function of amphibians, few studies have focused on the changes in its composition and function. In the present study, we identified the variation in adaptive immunity, as well as the corresponding changes in skin microbiome of Bufo raddei living in a heavy metal polluted area. The adaptive immunity of B. raddei in heavy metal polluted area was significantly lower than that in relatively unpolluted area. Further, different skin bacterial communities were found in the two areas. In the heavy metal polluted area, Actinobacteria and Microbacterium were the dominant bacteria in the skin microbiome of B. raddei, which showed broad-spectrum antibacterial activity. Besides, the antibiotic synthesis was also increased in metabolic pathways. The present study suggested that the adaptive immunity of B. raddei was weakened under long-term heavy metal stress. However, the toads increased the abundance of bacteriostatic bacteria by regulating the composition of skin microbiome, which released a large number of bacteriostatic metabolites and enhanced the host resistance to external pathogens in turn. [ABSTRACT FROM AUTHOR]

Successful invasion and adaptation of bacteria into lichen symbiosis requires the involvement of a number of physiological mechanisms that regulate interactions between bacteriobionts, mycobionts, and algobionts and ensure the optimization of thallus growth and development. The genomes of two lichen bacteriobionts, Lichenibacterium ramalinae and L. minor, were analyzed to identify those factors. No nodulation genes that are traditional for rhizobia were found. The TIGR02302 protein has been suggested to have a similar function. Genes encoding proteins associated with the implementation of planktonic and biofilm phenotypes—flagellins and pilins—have been found. These genes have a high level of similarity with the genes of plant symbiont bacteria. Genetic determinants of virulence factors such as locus B invasion proteins, integration host factor (IHF), sensory histidine kinases, siderophore receptor and transport proteins, and monooxygenase of antibiotic synthesis (Abm), were found in the genomes of the studied bacteria. The listed genes have similarities with those in organisms forming associations of different degrees with plants. Based on the data obtained, the assumption of a priority association of bacteria of the Lichenibacteriaceae family with green lichen algae was suggested. [ABSTRACT FROM AUTHOR]

Continuous-flow chemistry has become a mainstream process and a notable trend among emerging technologies for drug synthesis. It is routinely used in academic and industrial laboratories to generate a wide variety of molecules and building blocks. The advantages it provides, in terms of safety, speed, cost efficiency and small-equipment footprint compared to analog batch processes, have been known for some time. What has become even more important in recent years is its compliance with the quality objectives that are required by drug-development protocols that integrate inline analysis and purification tools. There can be no doubt that worldwide government agencies have strongly encouraged the study and implementation of this innovative, sustainable and environmentally friendly technology. In this brief review, we list and evaluate the development and applications of continuous-flow processes for antibiotic synthesis. This work spans the period of 2012–2022 and highlights the main cases in which either active ingredients or their intermediates were produced under continuous flow. We hope that this manuscript will provide an overview of the field and a starting point for a deeper understanding of the impact of flow chemistry on the broad panorama of antibiotic synthesis. [ABSTRACT FROM AUTHOR]

UDP-glycosyltransferases (UGTs) are the most studied glycosyltransferases, and belong to large GT1 family performing the key roles in antibiotic synthesis, the development of bacterial glycosyltransferase inhibitors, and in animal inflammation. They transfer the glycosyl groups from nucleotide UDP-sugars (UDP-glucose, UDP-galactose, UDP-xylose, and UDP-rhamnose) to the acceptors including saccharides, proteins, lipids, and secondary metabolites. The present review summarized the recent of UDP-glycosyltransferases, including their structures, functions, and catalytic mechanism, especially in edible fungi. The future perspectives and new challenges were also summarized to understand of their structure–function relationships in the future. The outputs in this field could provide a reference to recognize function, structure, and catalytic mechanism of UDP-glycosyltransferases for understanding the biosynthesis pathways of secondary metabolites, such as hydrocarbons, monoterpenes, sesquiterpene, and polysaccharides in edible fungi. [ABSTRACT FROM AUTHOR]

With the increasing resistance exhibited by undesirable bacteria to traditional antibiotics, the need to discover alternative (or, at least, supplementary) treatments to combat chemically resistant bacteria is becoming urgent. Quorum sensing (QS) refers to a novel bacterial communication system for monitoring cell density and regulation of a network of gene expression that is mediated by a group of signaling molecules called autoinducers (AIs). QSregulated multicellular behaviors include biofilm formation, horizontal gene transfer, and antibiotic synthesis, which are demonstrating increasing pathogenicity to plants and aquacultural animals as well as contamination of wastewater treatment devices. To inhibit QS-regulated microbial behaviors, the strategy of quorum quenching (QQ) has been developed. Different quorum quenchers interfere with QS through different mechanisms, such as competitively inhibiting AI perception (e.g., by QS inhibitors) and AI degradation (e.g., by QQ enzymes). In this review, we first introduce different signaling molecules, including diffusible signal factor (DSF) and acyl homoserine lactones (AHLs) for Gram-negative bacteria, AIPs for Grampositive bacteria, and AI-2 for interspecies communication, thus demonstrating the mode of action of the QS system. We next exemplify the QQ mechanisms of various quorum quenchers, such as chemical QS inhibitors, and the physical/enzymatic degradation of QS signals. We devote special attention to AHL-degrading enzymes, which are categorized in detail according to their diverse catalytic mechanisms and enzymatic properties. In the final part, the applications and advantages of quorum quenchers (especially QQ enzymes and bacteria) are summarized in the context of agricultural/aquacultural pathogen biocontrol, membrane bioreactors for wastewater treatment, and the attenuation of human pathogenic bacteria. Taken together, we present the state-of-the-art in research considering QS and QQ, providing theoretical evidence and support for wider application of this promising environmentally friendly biocontrol strategy. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a common bacteria that may cause a wide range of severe illnesses in humans. One of the nonantibiotic therapies, antivirulence factor therapy, has attracted ongoing interest. Screening for and investigating bacterial virulence factor inhibitors is critical for the development of antivirulence factor treatments. Pyocyanin is P. aeruginosa 's distinctive pigment, and it plays a key role in infection. The impact of low concentration ethanol on pyocyanin production was investigated in this research. Pyocyanin production was found both subjectively and quantitatively. The effects of ethanol on the expression of pyocyanin production genes were studied using qRT-PCR and western blotting. The findings demonstrated that low concentrations of ethanol (as little as 0.1%) greatly suppressed pyocyanin production without affecting P. aeruginosa growth. The degree of inhibition increased as the ethanol contentration rose. Ethanol inhibits the expression of genes involved in pyocyanin production. This inhibitory impact was mostly seen at the protein level. Further research revealed that ethanol increased the expression of the post-transcriptional regulator RsmA, which inhibits pyocyanin production. Given the favorable relationship between pyocyanin production and antibiotic resistance, the impact of low concentration ethanol on various antibiotics was investigated. Ethanol lowered antibiotic resistance in P. aeruginosa , presumably by inhibiting pyocyanin. [ABSTRACT FROM AUTHOR]

Termites’ digestive systems, particularly in lower termites with the presence of protozoa, are unique ecological niches that shelter a diverse microbiota with a variety of functions for the host and the environment. In 2012, the metagenomic DNA (5.4 Gb) of the prokaryotes that freely live in the gut of the lower termite Coptotermes gestroi were sequenced. A total of 125,431 genes were predicted and analyzed in order to mine lignocellulolytic genes. however, the overall picture of the structure, diversity, and function of the prokaryotic gut microbiota was not investigated. In the present study, these 125,431 genes were taxonomically classified by MEGAN and functionally annotated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and by the Carbohydrate-Active enZYmes (CAZy) and HMMER databases. As a result, 95,751 bacterial genes were classified into 35 phyla. The structure of the bacteria, typified by a high ratio of Firmicutes to Bacterioidetes, was distinct from the structure of the entirety of the bacteria in the lower or higher termites’ guts. The archaea (533 genes) were distributed into 4 phyla, 10 classes, 15 orders, 21 families, 47 genera, and 61 species. Although freely living in the guts, the prokaryotic community was formed, developed, and adapted to exhibit unique interactions in order to perform mutual roles of benefit to their hosts. Methanobacteriales, accounting for 61% of the archaea symbionts, seem to play an important role in methanogenesis. Concomitantly, bacterial methanotrophs in the gut utilize methane and combine with other bacterial groups, including potential lignocellulolytic degraders, acetogens, sulfur bacteria, and nitrogen-recycling bacteria, to efficiently convert wood with little nitrogen into acetates via certain pathway modules specified by prokaryotes that freely live in the gut. This forms an important energy source for the termites. Furthermore, bacteria carry 2223 genes involved in the biosynthesis of 17 antibiotic groups. The gut bacteria also possess genes for the degradation of 18 toxic aromatic compounds, of which four are commercial pesticides against termites commonly used for the preservation of wooden constructions. Eight of the eighteen pathways were the first to be reported from the termite gut. Overall, this study sheds light on the roles of the freely living bacteria and archaea in the C. gestroi gut, providing evidence that the gut microbiome acts as the second host genome, contributing both nutrients and immunity to support the host’s existence, growth, and development.