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This work examined the occurrence characteristics and ecological risks of 31 antibiotics across five classes and seven ARGs in the surface waters of Gaoyou Lake. A total of 27 antibiotics, spanning four classes, were detected in the surface waters of Gaoyou Lake, with an overall concentration ranging from 57.5 to 114 ng/L and an average of 78.8 ng/L. Sulfonamide antibiotics exhibited the highest average concentration at 32.7 ng/L. Spatial analysis revealed that antibiotic concentration levels in the western region of the lake were higher than those in other areas. Similarly, ARGs were most abundant in this area, with sulfonamide ARGs demonstrating a notably higher mean abundance than other ARGs. Correlation analysis revealed strong positive associations between sul1 and several antibiotics, including sulfadimidine, sulfamethoxazole, ciprofloxacin, lincomycin, clindamycin, erythromycin, and intl1 (P < 0.05), with intra-group correlations among sulfonamide ARGs exceeding those between different ARG groups. Ecological risk assessment indicated that erythromycin and sulfamethoxazole presented medium risks, whereas roxithromycin, azithromycin, and lincomycin were associated with low risks to aquatic organisms. The ecological risk proportions across monitoring sites were primarily low (10.6%) and moderate (16.7%), with no high-risk areas identified and 72.7% presenting no risk. The cumulative ecological risk quotient (RQcum) suggested a medium-risk level at all surveyed sites. [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]

Key message: A GLK homologue was identified and functionally characterized in Catharanthus roseus. Silencing CrGLK with VIGS or the chloroplast retrograde signaling inducer lincomycin increased terpenoid indole alkaloid biosynthesis. Catharanthus roseus is the sole source of the chemotherapeutic terpenoid indole alkaloids (TIAs) vinblastine and vincristine. TIA pathway genes, particularly genes in the vindoline pathway, are expressed at higher levels in immature versus mature leaves, but the molecular mechanisms responsible for this developmental regulation are unknown. We investigated the role of GOLDEN2-LIKE (GLK) transcription factors in contributing to this ontogenetic regulation since GLKs are active in seedlings upon light exposure and in the leaf’s early development, but their activity is repressed as leaves age and senesce. We identified a GLK homologue in C. roseus and functionally characterized its role in regulating TIA biosynthesis, with a focus on the vindoline pathway, by transiently reducing its expression through two separate methods: virus-induced gene silencing (VIGS) and application of chloroplast retrograde signaling inducers, norflurazon and lincomycin. Reducing CrGLK levels with each method reduced chlorophyll accumulation and the expression of the light harvesting complex subunit (LHCB2.2), confirming its functional homology with GLKs in other plant species. In contrast, reducing CrGLK via VIGS or lincomycin increased TIA accumulation and TIA pathway gene expression, suggesting that CrGLK may repress TIA biosynthesis. However, norflurazon had no effect on TIA gene expression, indicating that reducing CrGLK alone is not sufficient to induce TIA biosynthesis. Future work is needed to clarify the specific molecular mechanisms leading to increased TIA biosynthesis with CrGLK silencing. This is the first identification and characterization of GLK in C. roseus and the first investigation of how chloroplast retrograde signaling might regulate TIA biosynthesis. [ABSTRACT FROM AUTHOR]

The Actinomycetes Streptomyces lincolnensis is the producer of lincosamide-type antibiotic lincomycin, a widely utilized drug against Gram-positive bacteria and protozoans. In this work, through gene knockout, complementation, and overexpression experiments, we identified LcbR1 (SLINC_1595), a GntR family transcriptional regulator, as a repressor for lincomycin biosynthesis. Deletion of lcbR1 boosted lincomycin production by 3.8-fold, without obvious change in morphological development or cellular growth. The homologues of LcbR1 are widely distributed in Streptomyces. Heterologous expression of SCO1410 from Streptomyces coelicolor resulted in the reduction of lincomycin yield, implying that the function of LcbR1 is conserved across different species. Alignment among sequences upstream of lcbR1 and their homologues revealed a conserved 16-bp palindrome (-TTGAACGATCCTTCAA-), which was further proven to be the recognition motif of LcbR1 by electrophoretic mobility shift assays (EMSAs). Via this motif, LcbR1 suppressed the transcription of lcbR1 and SLINC_1596 sharing the same bi-directional promoter. SLINC_1596, one important target of LcbR1, exerted a positive effect on lincomycin production. As detected by quantitative real-time PCR (qRT-PCR) analyses, the expressions of all selected structural (lmbA, lmbC, lmbJ, lmbV, and lmbW), resistance (lmrA and lmrB) and regulatory genes (lmrC and lmbU) from lincomycin biosynthesis cluster were upregulated in deletion strain ΔlcbR1 at 48 h of fermentation, while the mRNA amounts of bldD, glnR, ramR, SLCG_Lrp, and SLCG_2919, previously characterized as the regulators on lincomycin production, were decreased in strain ΔlcbR1, although the regulatory effects of LcbR1 on the above differential expression genes seemed to be indirect. Besides, indicated by EMSAs, the expression of lcbR1 might be regulated by GlnR, SLCG_Lrp, and SLCG_2919, which shows the complexity of the regulatory network on lincomycin biosynthesis. Key points: • LcbR1 is a novel and conservative GntR family regulator regulating lincomycin production. • LcbR1 modulates the expressions of lcbR1 and SLINC_1596 through a palindromic motif. • GlnR, SLCG_Lrp, and SLCG_2919 can control the expression of lcbR1. [ABSTRACT FROM AUTHOR]

Lincomycin, a clinically important antibiotic against Gram-positive bacteria, is a sulfur-containing metabolite produced by Streptomyces lincolnensis. The main problem in the fermentation is the high content of lincomycin B, which is a by-product of insufficient methylation by S-adenosylmethionine (SAM) dependent methyltransferase. In this study, the content of lincomycin B was decreased from 4.04% to 0.75% and from 8.20% to 5.78% by the addition of NaCl as an osmotic regulator in flask and 15 L bioreactor fermentation, respectively. By analysis of the sulfur-containing metabolites (cysteine, homocysteine, SAM, and ergothioneine) and high-throughput RNA sequencing, the mechanism of osmotic regulation on lincomycin fermentation was studied. The results showed that the synthesis of methyl donor (SAM) and sulfur donor of lincomycin (ergothioneine and mycothiol) were increased at the metabolite level and transcription level under osmotic stimulation; the transcription of genes involved in sulfur assimilation (tauA, ssuA1B1C1) and lincomycin biosynthesis were also up-regulated significantly. This study provides a cost-effective method to reduce lincomycin B and increase the production of lincomycin A. The mechanisms of osmotic pressure regulation on lincomycin fermentation was also elucidated, which may provide more genetically modified targets for overproduction of lincomycin and other sulfur containing secondary metabolites. [ABSTRACT FROM AUTHOR]

Lincomycin (LC) is an extensively applied broad-spectrum antibiotic, and its considerable residues in wastewater have caused a series of environmental problems, which makes degradation of LC wastewater extremely urgent. In this work, we have constructed a novel boron nitride (BN) and samarium (Sm) co-modified Ti/PbO2 as anode for high-performance degradation of LC wastewater. Compared with Ti/PbO2, Ti/PbO2-Sm, and Ti/PbO2-BN electrodes, Ti/PbO2-BN-Sm electrode with smaller pyramidal particles possesses higher oxygen evolution potential (2.32 V), excellent accelerated service life (103 h), and outstanding electrocatalytic activity. The single-factor experiments demonstrate that under optimized conditions (current density of 20 mA.cm-2, 6.0 g L-1 Na2SO4, pH 9, and temperature of 30°C), removal rate and COD degradation rate of LC at 3 h have reached 92.85% and 89.11%, respectively. At the same time, degradation of LC is in accordance with the primary kinetic model. Based on the analysis of high-performance liquid chromatography-mass spectrometry (HPLC-MS), four possible degradation pathways are hypothesized. Therefore, efficient electrochemical degradation of LC by using an extremely long-life Ti/PbO2 electrode with high catalytic activity may be a promising method. [ABSTRACT FROM AUTHOR]

In order to preliminarily explore the distribution of antibiotic pollution in the coastal waters of eastern China, the concentrations of 13 antibiotics in 5 representative coastal rivers in Jiangsu and 21 sampling sites in the coastal waters of Jiangsu were analyzed. The total antibiotic concentrations in the 5 rivers ranged from 33.14 to 417.78 ng L−1, and the total antibiotic concentrations in the 21 sampling sites ranged from 0.90 to 86.33 ng L−1. Macrolides exhibited the highest total concentration and the maximum detection frequency in both coastal rivers and the coastal waters. The concentrations of antibiotics in a sampling site decreased as the distance of the sampling site from the coastline increased, indicating that river inputs are important sources of antibiotic pollution in the coastal waters of Jiangsu. The detection frequencies of roxithromycin, lincomycin, azithromycin, and sulfamethoxazole in the rivers and sampling sites were above 70%. Correlation analysis showed that the concentrations of antibiotics were positively correlated with the levels of chemical oxygen demand, total phosphorus, and total nitrogen. Risk assessments revealed that roxithromycin and ofloxacin posed medium ecological and resistance risks, respectively, to the most sensitive aquatic organisms in the coastal waters of Jiangsu. The results of this study highlight the significance of monitoring and controlling the concentrations of antibiotic contaminants in the coastal waters of Jiangsu. [ABSTRACT FROM AUTHOR]

Lincomycin is a broad-spectrum antibiotic and particularly effective against Gram-positive pathogens. Albeit familiar with the biosynthetic mechanism of lincomycin, we know less about its regulation, limiting the rational design for strain improvement. We therefore analyzed two-component systems (TCSs) in Streptomyces lincolnensis, and selected eight TCS gene(s) to construct their deletion mutants utilizing CRISPR/Cas9 system. Among them, lincomycin yield increased in two strains (Δ3900–3901 and Δ5290–5291) while decreased in other four strains (Δ3415–3416, Δ4153–4154, Δ4985, and Δ7949). Considering the conspicuous effect, SLINC_5291-5290 (AflQ1-Q2) was subsequently studied in detail. Its repression on lincomycin biosynthesis was further proved by gene complementation and overexpression. By binding to a 16-bp palindromic motif, the response regulator AflQ1 inhibits the transcription of its encoding gene and the expression of eight operons inside the lincomycin synthetic cluster (headed by lmbA, lmbJ, lmbK, lmbV, lmbW, lmbU, lmrA, and lmrC), as demonstrated by quantitative RT-PCR and electrophoretic mobility shift assays. Besides, the regulatory genes including bldD, glnR, lcbR1, and ramR are also regulated by the TCS. According to the screening towards nitrogen sources, aspartate affects the regulatory behavior of histidine kinase AflQ2. And in return, AflQ1 accelerates aspartate metabolism via ask-asd, asd2, and thrA. In summary, we acquired six novel regulators related to lincomycin biosynthesis, and elucidated the regulatory mechanism of AflQ1-Q2. This highly conserved TCS is a promising target for the construction of antibiotic high-yield strains. Key points: • AflQ1-Q2 is a repressor for lincomycin production. • AflQ1 modulates the expression of lincomycin biosynthetic and regulatory genes. • Aspartate affects the behavior of AflQ2, and its metabolism is promoted by AflQ1. [ABSTRACT FROM AUTHOR]

Streptomyces albus J1074 is one of the most popular heterologous expression platforms among streptomycetes. Identification of new genes and mutations that influence specialized metabolism in this species is therefore of great applied interest. Here, we describe S. albus KO-1304 that was isolated as a spontaneous lincomycin-resistant variant of double rpsLR94GrsmGR15SG40E mutant KO-1295. Besides altered antibiotic resistance profile, KO-1304 exhibited increased antibiotic activity as compared to its parental strains. KO-1304 genome sequencing revealed mutations within gene XNR_2147 encoding putative TetR-like protein. Gene XNR_2146 for efflux protein is the most likely target of repressing action of Xnr_2147. Our data agree with the scenario where lincomycin resistance phenotype of KO-1304 arose from inability of mutated Xnr_2147 protein to repress XNR_2146. Introduction of additional copy of XNR_2146 into wild type strain increased antibiotic activity of the latter, attesting to the practical value of transporter genes for strain improvement. [ABSTRACT FROM AUTHOR]

The South Saskatchewan River Basin (SSRB) is considered one of the most intensively farmed regions in Canada, with high densities of livestock and expansive areas of irrigated cropland. We measured concentrations of seven veterinary antimicrobials (VAs) in 114 surface water samples from feedlot environs and 219 samples from irrigation conveyances in the SSRB. Overall, detection frequencies in feedlot environs were 100% for chlortetracycline (CTC) and tetracycline (TC), 94% for monensin (MON), 84% for tylosin (TYL), 72% for lincomycin (LIN), 66% for erythromycin (ERY), and 23% for sulfamethazine (SMZ). For irrigation conveyances, detection frequencies for CTC and TC remained high (94–100%), but dropped to 18% for ERY, 15% for TYL, 10% for MON, and 4% for SMZ. Lincomycin was not detected in irrigation conveyance water. Maximum concentrations of VAs ranged from 1384 µg L−1 (TC) to 17 ng L−1 (SMZ) in feedlot environs while those in irrigation conveyances were 155 ng L−1 (TC) to 29 ng L−1 (ERY). High detection frequencies and median concentrations of VAs in both feedlot environs and irrigation conveyances were associated with high amounts of precipitation. However, an irrigation district (ID) with high livestock density (Lethbridge Northern) did not exhibit higher concentrations of VAs compared to IDs with less livestock, while levels of VAs in irrigation conveyances were less influenced by the degree of surface runoff. The ubiquity of CTC and TC in our study is likely a reflection of its widespread use in intensive livestock operations. Additional investigation is required to link environmental concentrations of VAs with livestock densities and increase our understanding of potential antimicrobial resistance in high-intensity agroecosystems. [ABSTRACT FROM AUTHOR]

A novel electrochemiluminescence (ECL) aptasensor for the determination of lincomycin (LIN) was developed based on CdS QDs/carboxylated g-C3N4 (CdS QDs/C-g-C3N4). CdS QDs/C-g-C3N4 served as the substrate of the aptasensor, and then CdS QDs/C-g-C3N4-modified electrode was incubated with aptamer DNA (Apt-DNA). When the non-specific sites of the electrode surface was blocked by 6-mercaptohexanol, the ferrocene-labeled probe (Fer-DNA) was assembled onto the electrode surface through base complementation with Apt-DNA. In the absence of LIN, the ECL signal was quenched effectively by Fer-DNA and a decreased ECL emission (off state) was acquired. On the contrary, LIN was specifically bond with Apt-DNA, and Fer-DNA was detached from the aptasensor surface because of the deformation of Apt-DNA, resulting in an effectively enhanced ECL signal (on state). The constructed ECL aptasensor exhibited a wide detection range for LIN determination (0.05 ng mL−1–100 μg mL−1) with a low detection limit (0.02 ng mL−1). Importantly, the proposed ECL aptasensor showed outstanding accuracy and specificity for LIN determination, and also provided a potential strategy for other antibiotic determinations. [ABSTRACT FROM AUTHOR]

A novel electrochemiluminescence (ECL) aptasensor for the determination of lincomycin (LIN) was developed based on CdS QDs/carboxylated g-C3N4 (CdS QDs/C-g-C3N4). CdS QDs/C-g-C3N4 served as the substrate of the aptasensor, and then CdS QDs/C-g-C3N4-modified electrode was incubated with aptamer DNA (Apt-DNA). When the non-specific sites of the electrode surface was blocked by 6-mercaptohexanol, the ferrocene-labeled probe (Fer-DNA) was assembled onto the electrode surface through base complementation with Apt-DNA. In the absence of LIN, the ECL signal was quenched effectively by Fer-DNA and a decreased ECL emission (off state) was acquired. On the contrary, LIN was specifically bond with Apt-DNA, and Fer-DNA was detached from the aptasensor surface because of the deformation of Apt-DNA, resulting in an effectively enhanced ECL signal (on state). The constructed ECL aptasensor exhibited a wide detection range for LIN determination (0.05 ng mL−1–100 μg mL−1) with a low detection limit (0.02 ng mL−1). Importantly, the proposed ECL aptasensor showed outstanding accuracy and specificity for LIN determination, and also provided a potential strategy for other antibiotic determinations. [ABSTRACT FROM AUTHOR]

Staphylococcus equorum strain KM1031 is resistant to chloramphenicol, erythromycin and lincomycin. To shed light on the genetic factors underlying these antibiotic resistances, we determined the global gene expression profile of S. equorum KM1031 using RNA sequencing. During chloramphenicol, erythromycin and lincomycin treatment, 8.3% (183/2,336), 16.0% (354/2,336), and 2.9% (63/2,336) of S. equorum KM1031 genes exhibited significant differences in expression, respectively. These three antibiotics upregulated genes related to efflux and downregulated genes related to transporters. Antibiotic treatment also upregulated osmoprotectant-related genes involved in salt tolerance. To identify specific genes functionally related to antibiotic resistance, we compared the genome of strain KM1031 with those of three S. equorum strains that are sensitive to these three antibiotics. We identified three genes of particular interest: an antibiotic biosynthesis monooxygenase gene (abm, AWC34_RS01805) related to chloramphenicol resistance, an antibiotic ABC transporter ATP-binding protein gene (msr, AWC34_RS11115) related to erythromycin resistance, and a lincosamide nucleotydyltransferase gene (lnuA, AWC34_RS13300) related to lincomycin resistance. These genes were upregulated in response to the corresponding antibiotic; in particular, msr was upregulated more than fourfold by erythromycin treatment. Finally, the results of RNA sequencing were validated by quantitative real-time PCR. This transcriptomic analysis provides genetic evidence regarding antibiotic stress responses of S. equorum strain KM1031. [ABSTRACT FROM AUTHOR]

Neomycin and lincomycin are widely used in the treatment of infections illnesses. However, the irrational and inappropriate of antibiotics contributes to threaten human health seriously. We developed a rapid and multiple detection strategy for trace amounts of neomycin (NEO) and lincomycin (LIN) in milk using Surface-Enhanced Raman Spectroscopy (SERS)-based lateral flow assay (LFA). The method used two SERS immunoprobes (a probe for NEO and a probe for LIN) were mixed and applied to the conjugate pad, and then, the NEO-OVA and LIN-OVA were mixed and coated on LFA as the only test line. Simultaneous quantitative detection of NEO and LIN was achieved by detecting the Raman intensity of captured immunoprobes on test line using a Raman spectrometer. Under optimized condition, NEO and LIN could be detected as low as 0.33 pg/mL and 0.29 pg/mL in 15 min with a sample volume of 100 μL. The practicality of the LFA in milk sample was also validated. The method is highly sensitive, accurate, and effective. It has a good chance to be employed for multiple antibiotics detection in food products. [ABSTRACT FROM AUTHOR]

European foulbrood (EFB) is a disease of honey bee larvae caused by Melissococcus plutonius. In North America, oxytetracycline (OTC) is approved to combat EFB disease though tylosin (TYL) and lincomycin (LMC) are also registered for use against American foulbrood disease. Herein, we report and characterize an OTC-resistant M. plutonius isolate from British Columbia, Canada, providing an antimicrobial sensitivity to the three approved antibiotics and studying their abilities to alter larval survival in an in vitro infection model. Specifically, we investigated OTC, TYL, and LMC as potential treatment options for EFB disease using laboratory-reared larvae infected with M. plutonius. The utility of the three antibiotics were compared through an experimental design that either mimicked metaphylaxis or antimicrobial intervention. At varying concentrations, all three antibiotics prevented clinical signs of EFB disease following infection with M. plutonius 2019BC1 in vitro. This included treatment with 100 μg/mL of OTC, a concentration that was ~ 3× the minimum inhibitory concentration measured to inhibit the strain in nutrient broth. Additionally, we noted high larval mortality in groups treated with doses of OTC corresponding to ~ 30× the dose required to eliminate bacterial growth in vitro. In contrast, TYL and LMC were not toxic to larvae at concentrations that exceed field use. As we continue to investigate antimicrobial resistance (AMR) profiles of M. plutonius from known EFB outbreaks, we expect a range of AMR phenotypes, reiterating the importance of expanding current therapeutic options along with alternative management practices to suppress this disease. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that antibiotic administration causes gut injury, negatively affecting nutrient digestion, immune regulation, and colonization resistance against pathogens due to the disruption of gut microbiota. However, the time-course effects of therapeutic antibiotics on alterations of gut microbes and short-chain fatty acids (SCFAs) in young swine are still unknown. In this study, twenty piglets were assigned into two groups and fed commercial diets with or without lincomycin in the first week for a 28-day trial period. Results showed that 1-week lincomycin exposure (LE) did reduce the body weight on day 14 (p = 0.0450) and 28 (p = 0.0362). The alpha-diversity notably reduced after 1-week LE, and then gradually raised and reached the control group level in the second week on cessation of LE, indicated by the variation of Sobs, Chao, Shannon, and ACE index (p < 0.05). Beta-diversity analysis revealed that the distinct microbial cluster existed persistently for the whole trial period between two groups (p < 0.001). The relative abundance of most microbes including fiber-degrading (e.g., Agathobacter and Coprococcus), beneficial (e.g., Lactobacillus and Mitsuokella), or pathogenic bacteria (e.g., Terrisporobacter and Lachnoclostridium) decreased (LDA score > 3), and the concentration of SCFAs also diminished in the feces of 1-week lincomycin-administrated young swine, indicating that therapeutic LE killed most bacteria and reduced SCFA production with gut dysbiosis occurring. After the LE stopped, the state of gut dysbiosis gradually attenuated and formed new gut-microbe homeostasis distinct from microbial homeostasis of young pigs unexposed to lincomycin. The increased presence of potential pathogens, such as Terrisporobacter, Negativibacillus, and Escherichia-Shigella, and decreased beneficial bacteria, such as Lactobacillus and Agathobacter, were observed in new homeostasis reshaped by short-lincomycin administration (LDA score > 3 or p < 0.05), adversely affecting gut development and health of young pigs. Collectively, these results suggested that severe disruption of the commensal microbiota occurred after short-term LE or termination of LE in young swine. Key points: • Therapeutic lincomycin exposure induced gut dysbiosis, killing most bacteria and reducing short-chain fatty acid production. • Gut dysbiosis gradually attenuated and formed new homeostasis after lincomycin exposure stopped. • The new homeostasis, increased Escherichia-Shigella etc. and decreased Lactobacillus etc., was potentially harmful to gut health. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to investigate the antibacterial activity and mechanisms of plectasin-derived peptide NZ2114 in vitro and its therapeutic effects in vivo on broilers challenged with Clostridium perfringens. In vitro assay showed that NZ2114 had potent (minimal inhibitory concentration, 0.91 μM) and rapid antibacterial activity (99.9% reduction within 2 h), and the dual antibacterial mechanisms (including interfering with the cell membrane and intracellular DNA) against C. perfringens CVCC 2030. In vivo study, NZ2114 tended to increase linearly and quadratically the average daily gain as NZ2114 level increased and was the highest at 20 mg/L. NZ2114 at 10 ~ 40 mg/L dramatically reduced jejunal lesion score. Besides, the levels of IL-6, TNF-α, and IL-1β tended to downregulate linearly and quadratically as the NZ2114 level increased and were all the lowest at the dose of 20 mg/L. NZ2114 significantly upregulated those levels of IgA, IgG, IgM, and sIgA with a linear and quadratic dose effect, with the highest IgA, IgG, IgM, and sIgA at 20 mg/L. Finally, NZ2114 tended to linearly and quadratically increase the numerical value of crypt depth, with the lowest value at 40 mg/L. Lincomycin only dramatically reduced the jejunal lesion score and increased the numerical value of crypt depth. These results indicate that NZ2114 has the potential as a new alternative to antibiotics for the treatment of C. perfringens–induced necrotic enteritis infection. Key points • NZ2114 could kill C. perfringens by dual antibacterial mechanisms • Broiler necrotic enteritis model induced by C. perfringens was established • NZ2114 treatment could ameliorate C. perfringens–induced necrotic enteritis [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the efficiency of NiO/WO3 heterostructure photocatalytic process for removal of lincomycin antibiotic from aqueous solutions. WO3, NiO, and NiO/WO3 particles were synthesized and characterized by several techniques. NiO and WO3 photocatalytic properties in removal of lincomycin antibiotic were evaluated from experimental and theoretical perspectives. The influence of various parameters such as type of irradiation and photocatalyst, initial concentration of lincomycin (mg/L), NiO loading percentage (wt %), mass of NiO/WO3 (g), time (h), and pH were investigated. According to the results, the interaction energy for lincomycin adsorbed on NiO surface was –114.717 kJ mol–1 and for adsorbed on WO3 surface was –28.379 kJ mol–1. It is apparent from these interaction energy values that lincomycin adsorbed on WO3 surface has more negative Eint values and stronger interactions as compared to NiO surface. According to the experimental and theoretical results, loading of NiO onto WO3 increased the catalyst adsorption to lincomycin and ultimately increased the removal efficiency. The results shown that pH plays an important role in the removal of lincomycin. The maximum removal efficiency of 98.56% was obtained at pH 5, 0.2 g NiO/WO3 (2 wt %), 25 mg/L initial lincomycin concentration and 2 h exposure under sunlight. [ABSTRACT FROM AUTHOR]

Background: Livestock manure is an important reservoir of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs). The bacterial community structure and diversity are usually studied using high-throughput sequencing that cannot provide direct evidence for ARB changes. Thus, little is known about the distribution of ARB, especially in the presence of different antibiotics in composting process. In this study, the fate of ARB was investigated in aerobic composting of swine manure, using chlortetracycline, sulfamethoxazole, lincomycin, and ciprofloxacin as typical antibiotics. The abundance and species of ARB were analyzed systematically to evaluate their ecological risk at different stages of composting. Results: The absolute abundance of total ARB decreased, while the relative abundance increased on day 2. The relative abundance of lincomycin-resistant bacteria was higher than other ARBs during the whole composting process. The absolute abundance of four ARBs was 9.42 × 106–2.51 × 102 CFU/g (lincomycin- > chlortetracycline- > sulfamethoxazole- > ciprofloxacin- > multiple antibiotic-resistant bacteria), and they were not completely inactivated at the end of composting. Antibiotics led to a partial proliferation of ARBs including Corynebacterium, Sporosarcina, Solibacillus, and Acinetobacter. Especially, Corynebacterium, a pathogenic genus, was observed in chlortetracycline and lincomycin treatments. Conclusion: Among the antibiotics studied, lincomycin showed the highest ecological risk, due to it expanded the range of lincomycin-resistant bacteria at the phyla level (Firmicutes, Actinobacteria, and Proteobacteria). The principal co-ordinates analysis indicated that the bacterial community structure was primarily associated with the composting stages rather than antibiotic types. Possible potential hosts and the related to the decrease of ARGs abundance were indicated based on the network analysis. The decrease of culturable Proteobacteria and the increase of culturable Firmicutes (Solibacillus, Bacillus) partially explained the high degradation rate of various ARGs with the progress of composting in this study. These results provided important information for the control of antibiotic resistance in composting. [ABSTRACT FROM AUTHOR]

This study evaluated the occurrence of PPCPs in Cau River (Vietnam). Surface water and sediment samples were collected to determine PPCP concentrations. The analysis results showed the presence of 36 out of 56 investigated PPCPs in samples. The total concentration of PPCPs in water samples ranged from 8.21 to 529 ng/L and the value observed in sediment was from 17.4 to 172.8 μg/kg. Along the Cau River, there was a trend of accumulation of PPCPs at the downstream. The highest level of PPCP was observed after the river flows through Thai Nguyen and Bac Ninh provinces. Among detected PPCPs, the ones detected with high frequency (over 70%) and high concentration were caffeine, sulfamethoxazole, and lincomycin in water and triclocarban, levofloxacin, and griseofulvin in sediment. The water-sediment partition coefficient (Kd) was estimated to explore the fate of PPCP in the river, and the observed Kd mean values for lincomycin, sulfamethoxazole, and griseofulvin were 223.0, 7.6, and 997.0 kg/L, respectively. Risk assessment was initially conducted by applying a semi-quantitative assessment risk quotient (RQ); the potential ecological risk to the aquatic organism of PPCPs posed a moderate risk. [ABSTRACT FROM AUTHOR]

Antibiotic residues and antimicrobial resistance in surface water are issues of global concern, especially in developing countries. In this study, the occurrence of seven antibiotics and one antiparasitic agent was determined in surface water samples collected from four rivers running through Hanoi urban area in the Red River Delta, northern Vietnam. The pharmaceuticals in water samples were analyzed by solid-phase extraction combined with liquid chromatography–tandem mass spectrometry method. The concentrations of pharmaceuticals in our samples ranged from 3050 to 16,700 (median 7800) ng/L, which were generally higher than levels found in river water from many other locations in the world. Amoxicillin, oxfendazole, and lincomycin were the most dominant and frequently detected compounds (detection rate 100%), which together accounted for 76 ± 14% of total concentrations. Sulfacetamide and sulfamethoxazole were detected at moderate concentrations in more than two-thirds of the analyzed samples. The remaining antibiotics (i.e., azithromycin, ciprofloxacin, and ofloxacin) were found at lower detection frequency and concentrations. Antibiotic concentrations in the water samples were not significantly different between the investigated rivers. Meanwhile, levels of pharmaceuticals in the samples collected in February 2020 were higher than those found in the remaining samples, largely due to the sharp decrease in sulfamethoxazole and azithromycin concentrations of the samples collected in March and April. Considerable ecological risks of antibiotics in surface water were estimated for some compounds such as amoxicillin, ciprofloxacin, and ofloxacin. [ABSTRACT FROM AUTHOR]

The removal of lincomycin (LIN) from aqueous solution by birnessite was investigated by batch experiments. When the dosage of birnessite is 500 mg L−1 and the initial concentration of LIN is 15.5 μmol L−1, more than 90% of LIN was removed within 240 min at pH 4.90. Under different conditions, the reactions were well fitted with the second-order model (R2 > 0.95). The removal kinetics and the reaction mechanism were described. The presence of cations (e.g., K+, Ca2+, Mg2+, Fe2+, and Mn2+) inhibited the removal of LIN by birnessite, following the order: Mn2+ > Fe2+ > Ca2+ > Mg2+ > K+ ≈ Na+, due to the sorption of cations on birnessite, companying with the electron transfer and precipitation of oxides (for Mn2+ and Fe2+). The addition of Cu2+, SO42−, or NO3− improved the reactions. The presence of Cu2+ could oxidize antibiotics, and the repulsion between SO42−or NO3− and birnessite might disperse the birnessite suspensions during the reactions. Mn(IV) and Mn(III) were the core Mn species that play an important role in LIN removal. These findings will help to understand the removal process of LIN and illustrate the influence of cations and anions on the removal of similar pollutants by birnessite. [ABSTRACT FROM AUTHOR]

It is necessary to study the contamination of antibiotics in natural water bodies and assess its impact on ecological and human risks because of the large-scale use in the world. The occurrence and distribution characteristics of 45 antibiotics in reservoirs in Dongguan were investigated. Approximately, 77.8% of the detectable concentration of 35 antibiotics were found in the evaluation samples with concentration ranged from not detected (ND) to 729.59 ng/L, and dehydrated erythromycin was the highest one that appeared in Tongsha Reservoir. Fluoroquinolones and tetracyclines were the most abundant antibiotics with the detection frequency of 100% at sum concentration of 7.23–212.43 ng/L and 13.46–72.66 ng/L, respectively. Macrolides had a lower detected frequency but with highest concentration level at five kinds of antibiotics. Sulfamethoxazole, lincomycin, dehydrated erythromycin, pefloxacin, and panofloxacin were selected as important evaluation indicators. Sulfaguanidine, sulfamethoxazole, sulfisoxazole, dehydrated erythromycin, and clarithromycin that showed a significant correlation with Cl− and SO42− indicated that the pollution source of these antibiotics may be related to wastewater treatment plants. Among detected antibiotics, trimethoprim, norfloxacin, sarafloxacin, lincomycin, oxytetracycline, novobiocin, dehydrated erythromycin, and clarithromycin presented high risk to aquatic ecosystem in the reservoirs. There was no risk to humans at different ages of detected antibiotics, but it should attract attention because of the cumulative effects of antibiotics, which may cause potential risks to the human body. [ABSTRACT FROM AUTHOR]

Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in Streptomyces lincolnensis, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (lmbA and lmbV), three resistance genes (lmrA, lmrB and lmrC), and a regulatory gene (lmbU) within the lincomycin biosynthetic gene (lin) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene SLCG_3127 encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of SLCG_3127 and SLCG_Lrp was precisely identified. Inactivation of SLCG_3127 in S. lincolnensis resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside lin cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation. [ABSTRACT FROM AUTHOR]

Anti-inflammatory, analgesic, and leukocyte mobilization activities of ciprofloxacin, lincomycin, and erythromycin were evaluated in this study. The study involved two sets of thirty-three adult female Wistar rats assigned into five treatments, grouped into eleven of three rats per group. For agar-induced paw edema, the first three groups were treated 10 mg/kg, 20 mg/kg, and 40 mg/kg of ciprofloxacin, next three groups same doses of lincomycin, next three groups same doses of erythromycin, the tenth group received the reference drug, indomethacin 5 mg/kg while the last group 5 mg/kg normal saline. The analgesic activities group treatments were first nine groups received the three antibiotics in the same trend but at different doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. The tenth group received acetylsalicylic acid (Asp 100 mg/kg) while the last group received normal saline (5 ml/kg). Erythromycin had minimal effect on rat paw edema with non-significant inhibition. Ciprofloxacin and lincomycin suppressed agar-induced rat paw edema both at early and later phases of edema. Remarkably, lincomycin was most effective. Whereas lincomycin suppressed the action of phospholipase A2 with increasing concentration, erythromycin and ciprofloxacin best inhibited the enzyme at their lowest concentrations. Whereas ciprofloxacin had an analgesic effect, lincomycin and erythromycin did not exhibit analgesic effects. The three antibiotics significantly reduced leucocyte mobilization into the affected tissue especially at the highest dose (40 mg kg−1). Conclusively, based on our findings, we suggest that these antibiotics can be considered for use as anti-inflammatory and analgesic drugs. The testing drugs prevented leukocyte mobilization. [ABSTRACT FROM AUTHOR]

The residues of lincomycin (LIN), an antibiotic administered to aquatic animals, are often detected in aquatic environments. This study investigated effects of three environmental factors, sunlight, microbial activity, and temperature, on declines of spiked LIN in waters and sediment slurry samples collected from freshwater tilapia (Oreochromis mossambicus) and marine shrimp (Litopenaeus vannamei) culture ponds. The results showed that sunlight, temperature, and microbial activity all accelerated LIN transformation in the water and slurry samples. In matrixes of all water and slurry samples, LIN transformation was significantly faster under light conditions [half-life (t1/2) = 24–53 days] than under dark conditions (t1/2 = 154–2897 days). Microbial activity also accelerated LIN transformation; the t1/2 of LIN was shorter after nonsterile treatment (t1/2 = 12–809 days) than after sterile treatment (t1/2 = 154–2897 days). Moreover, LIN transformation was faster at 28 °C (t1/2 = 18–38 days) than at 20 and 12 °C (t1/2 = 34 and 462 days, respectively) in both slurry samples. The results revealed that LIN transformation in aquaculture pond water and sediment was either slow or stagnant. Sunlight, microbial activity, and temperature can accelerate LIN transformation to reduce LIN residue levels. [ABSTRACT FROM AUTHOR]

Global regulator BldA, the only tRNA for a rare leucine codon UUA, is best known for its ability to affect morphological differentiation and secondary metabolism in the genus Streptomyces. In this study, we confirmed the regulatory function of the bldA gene (Genbank accession no. EU124663.1) in Streptomyces lincolnensis. Disruption of bldA hinders the sporulation and lincomycin production, that can recur when complemented with a functional bldA gene. Western blotting assays demonstrate that translation of the lmbB2 gene which encodes a L-tyrosine hydroxylase is absolutely dependent on BldA; however, mistranslation of the lmbU gene which encodes a cluster-situated regulator (CSR) is observed in a bldA mutant. Intriguingly, when the preferential cognate codon CTG was used, the expression level of LmbU was not the highest compared to the usage of rare codon TTA or CTA, indicating the rare codon in this position is significant for the regulation of lmbU expression. Moreover, replacement of TTA codons in both genes with another leucin codon in the bldA mutant did not restore lincomycin production. Thus, we believe that the bldA gene regulates lincomycin production via controlling the translation of not only lmbB2 and lmbU, but also the other TTA-containing genes. In conclusion, the present study demonstrated the importance of the bldA gene in morphological differentiation and lincomycin production in S. lincolnensis. [ABSTRACT FROM AUTHOR]

Lincomycin forms cross-links within the peptidyl transferase loop region of the 23S ribosomal RNA (rRNA) of the 50S subunit of the bacterial ribosome, which is the site of peptide bond formation, thereby inhibiting protein synthesis. We have previously reported that lincomycin at concentrations below the minimum inhibitory concentration potentiates the production of secondary metabolites in actinomycete strains, suggesting that activation of these strains by utilizing the dose-dependent response of lincomycin could be used to effectively induce the production of cryptic secondary metabolites. Here, we aimed to elucidate the fundamental mechanisms underlying lincomycin induction of secondary metabolism in actinomycetes. In the present study, the dose-dependent response of lincomycin on gene expression of the model actinomycete Streptomyces coelicolor A3(2) and possible relationships to secondary metabolism were investigated. RNA sequencing analysis indicated that lincomycin produced enormous changes in gene expression profiles. Moreover, reverse transcription PCR and/or comparative proteome analysis revealed that in S. coelicolor A3(2), lincomycin, which was used at concentrations for markedly increased blue-pigmented antibiotic actinorhodin production, rapidly enhanced expression of the gene encoding the lincomycin-efflux ABC transporter, the 23S rRNA methyltransferase, and the ribosome-splitting factor to boost the intrinsic lincomycin resistance mechanisms and to reconstruct the probably stalled 70S ribosomes with lincomycin; and in contrast temporarily but dramatically reduced mRNA levels of housekeeping genes, such as those encoding FoF1 ATP synthase, RNA polymerase, ribosomal proteins, and transcription and translation factors, with an increase in intracellular NTPs. A possible mechanism for lincomycin induction of secondary metabolism in S. coelicolor A3(2) is discussed on the basis of these results. [ABSTRACT FROM AUTHOR]

A Gram-negative, rod-shaped, salt-tolerant, non-pigmented, and non-spore-forming bacterium, designated strain W1 (type strain CICC 23797 = CGMCC1.14949), was isolated from sewage samples of a dairy farm in Bozhou, Anhui, China. Strain W1 was resistant to lincomycin, troleandomycin, rifamycin, and vancomycin. Sequence analysis of the 16S rDNA gene revealed that the strain showed sequence similarity of 98.2% with the closest related species Serratia quinivorans CP6a. The genomic DNA G+C content of the isolate was 52.8 mol%. The biochemical characteristics of strain W1 assessed by the API 20E and Biolog GEN III analysis were different from those of the members of the genus Serratia. On the basis of the phenotypic and genotypic differences, strain W1 was proposed to be a novel Serratia species, Serratia bozhouensis sp. no v W1. [ABSTRACT FROM AUTHOR]

Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin biosynthesis. With nitrate supplementation, the transcription of nitrogen assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin exporter gene lmrA was found to be enhanced and positively regulated by the global regulator GlnR, whose expression was also improved. Moreover, heterologous expression of ABC2 transporter genes in Streptomyces coelicolor M145 resulted in an increased actinorhodin production. Further incorporation of a nitrite-specific transporter gene nirC, as in nirC-ABC2 cassette, led to an even higher actinorhodin production. Similarly, the titers of salinomycin, ansamitocin, lincomycin, and geldanamycin were increased with the integration of this cassette to Streptomyces albus BK3-25, Actinosynnema pretiosum ATCC31280, S. lincolnensis LC-G, and Streptomyces hygroscopicus XM201, respectively. Our work expanded the nitrate-stimulating effect to many antibiotic producers by utilizing the nirC- ABC2 cassette for enhanced nitrate utilization, which could become a general tool for titer increase of antibiotics in actinomycetes. [ABSTRACT FROM AUTHOR]

Although transcriptional activation of pathwayspecific positive regulatory genes and/or biosynthetic genes is primarily important for enhancing secondary metabolite production, reinforcement of substrate supply, as represented by primary metabolites, is also effective. For example, partial inhibition of fatty acid synthesis with ARC2 (an analog of triclosan) was found to enhance polyketide antibiotic production. Here, we demonstrate that this approach is effective even for industrial high-producing strains, for example enhancing salinomycin production by 40%, reaching 30.4 g/l of salinomycin in an industrial Streptomyces albus strain. We also hypothesized that a similar approach would be applicable to another important antibiotic group, nonribosomal peptide (NRP) antibiotics. We therefore attempted to partially inhibit protein synthesis by using ribosome-targeting drugs at subinhibitory concentrations (1/50∼1/2 of MICs), which may result in the preferential recruitment of intracellular amino acids to the biosynthesis of NRP antibiotics rather than to protein synthesis. Among the ribosome-targeting drugs examined, chloramphenicol at subinhibitory concentrations was most effective at enhancing the production by Streptomyces of NRP antibiotics such as actinomycin, calcium-dependent antibiotic (CDA), and piperidamycin, often resulting in an almost 2-fold increase in antibiotic production. Chloramphenicol activated biosynthetic genes at the transcriptional level and increased amino acid pool sizes 1.5- to 6-fold, enhancing the production of actinomycin and CDA. This 'metabolic perturbation' approach using subinhibitory concentrations of ribosome-targeting drugs is a rational method of enhancing NRP antibiotic production, being especially effective in transcriptionally activated (e.g., rpoB mutant) strains. Because this approach does not require prior genetic information, it may be widely applicable for enhancing bacterial production of NRP antibiotics and bioactive peptides. [ABSTRACT FROM AUTHOR]

In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, marbofloxacin, and sarafloxacin) and of their phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and consequently may help to reduce antimicrobial resistance in wastewaters. Nevertheless, the study also highlights that some PTPs may exhibit a higher ecotoxicity than the respective parent compounds. Consequently, UV treatment does not transform all micropollutants into harmless compounds and may not be a large-scale effluent treatment option. [ABSTRACT FROM AUTHOR]

Two novel and convenient methods for the determination of lincomycin (LCM) in aqueous solutions have been developed. The first method was based on the enhanced fluorescence of thioglycolic acidcapped CdTe quantum dots (TGA-CdTe QDs) by LCM. For the second method, the introduction of LCM could induce the aggregation of gold nanoparticles (AuNPs), displaying distinct changes in color and in UVvis spectra. Under optimal conditions, the enhanced fluorescence intensity was linearly proportional to LCM concentration in the range of 1-240 μg mL with a detection limit of 2.63 × 10 μg mL. The second platform is capable of determining LCM in ranges from 1.00 × 10 to 2.00 × 10 μg mL and from 3.00 × 10 to 1.20 × 10 μg mL with a detection limit of 1.27 × 10 μg mL. Both methods were used for rapid detection of LCM in real samples with satisfactory results. Comparisons between the two methods were made. [ABSTRACT FROM AUTHOR]

Low-molecular-mass thiols in organisms are well known for their redox-relevant role in protection against various endogenous and exogenous stresses. In eukaryotes and Gram-negative bacteria, the primary thiol is glutathione (GSH), a cysteinyl-containing tripeptide. In contrast, mycothiol (MSH), a cysteinyl pseudo-disaccharide, is dominant in Gram-positive actinobacteria, including antibiotic-producing actinomycetes and pathogenic mycobacteria. MSH is equivalent to GSH, either as a cofactor or as a substrate, in numerous biochemical processes, most of which have not been characterized, largely due to the dearth of information concerning MSH-dependent proteins. Actinomycetes are able to produce another thiol, ergothioneine (EGT), a histidine betaine derivative that is widely assimilated by plants and animals for variable physiological activities. The involvement of EGT in enzymatic reactions, however, lacks any precedent. Here we report that the unprecedented coupling of two bacterial thiols, MSH and EGT, has a constructive role in the biosynthesis of lincomycin A, a sulfur-containing lincosamide (C8 sugar) antibiotic that has been widely used for half a century to treat Gram-positive bacterial infections. EGT acts as a carrier to template the molecular assembly, and MSH is the sulfur donor for lincomycin maturation after thiol exchange. These thiols function through two unusual S-glycosylations that program lincosamide transfer, activation and modification, providing the first paradigm for EGT-associated biochemical processes and for the poorly understood MSH-dependent biotransformations, a newly described model that is potentially common in the incorporation of sulfur, an element essential for life and ubiquitous in living systems. [ABSTRACT FROM AUTHOR]

Production of lincomycin by Streptomyces lincolnensis was studied by varying medium composition and environmental conditions. With the medium composition optimized by statistical experimental design (45 g/L soluble starch, 15 g/L sugar cane molasses, 13.33 g/L peptone water, 6.67 g/L NaNO and 4.0 g/L CaCO), lincomycin production increased by 2 ∼ 3 fold compared to that obtained with un-optimized basal medium. Lincomycin production was further improved by optimizing culture conditions such as agitation speed, impeller type and pH under the optimized medium condition. The highest titer of 350 mg/L lincomycin was achieved from 240 h bioreactor culture. These results demonstrate that fermentation conditions for maximal lincomycin production by Streptomyces lincolnensis were optimized via biotechnological processes. [ABSTRACT FROM AUTHOR]

Interest in identifying pools of antibacterial-resistance genes has grown over the last decade, with veterinary antibiotics (VAs) receiving particular attention. In this paper, a mesoscale study aimed at evaluating the vertical transport of common VAs-namely, fluoroquinolones, tetracyclines, sulfonamides, and lincosamides in agricultural soil subjected to drip irrigation-was performed under greenhouse conditions. Accordingly, leachates of cropped and uncropped soil, amended with swine-slurry leading to 19-38 μg kg (dry mass) antibiotics in the soil, were analyzed over the course of the productive cycle of a lettuce (42 days) with three sampling campaigns ( N = 24). High lincomycin (LCM) concentrations (30-39 μg L) were detected in the leachates collected from the swine-slurry-amended soil. The highest LCM mass recovered in the leachates (30.1 ± 1.63 %) was obtained from cropped experimental units. In addition, the LCM leaching constant and its leaching potential as obtained from the first-order model were higher in the leachates from the cropped experimental units. Lower concentrations of sulfadimethoxine were also detected in leachates and in soil. Enrofloxacin and oxytetracycline occurred only in soil, which is consistent with high soil interaction. [ABSTRACT FROM AUTHOR]

Lincomycin 10 mg kg, IV in buffalo calves followed two-compartment open model with high distribution rate constant α (11.2 ± 0.42 h) and K/ K ratio (4.40 ± 0.10). Distribution half-life was 0.06 ± 0.01 h and AUC was 41.6 ± 1.73 μg mL h. Large Vd (1.15 ± 0.03 L kg) indicated good distribution of lincomycin in various body fluids and tissues. Peak plasma level of lincomycin (71.8 ± 1.83 μg mL) was observed at 1 min as expected by IV route. The elimination half-life and MRT of lincomycin were short (3.30 ± 0.08 and 4.32 ± 0.11 h, respectively). Lincomycin 10 mg kg IV at 12-h interval would be sufficient to maintain T > MIC above 60 % for bacteria with minimum inhibitory concentrations (MIC) values ≤1.6 μg mL. Favourable pharmacokinetic profile in buffalo calves and a convenient dosing interval suggest that lincomycin may be an appropriate antibacterial in buffalo species for gram-positive and anaerobic bacterial pathogens susceptible to lincomycin. [ABSTRACT FROM AUTHOR]

Elongation factor P (EF-P) is a highly conserved ribosomal initiation factor responsible for stimulating formation of the first peptide bond. Its essentiality has been debated and may differ depending on the organism. Here, we demonstrate that EF-P is dispensable in Escherichia coli and Pseudomonas aeruginosa under laboratory growth conditions. Although knockouts are viable, growth rates are diminished compared with wild-type strains. Despite this cost in fitness, these mutants are not more susceptible to a wide range of antibiotics; including ribosome targeting antibiotics, such as lincomycin, chloramphenicol, and streptomycin, which have been shown previously to disrupt EF-P function in vitro. In Pseudomonas, knockout of efp leads to an upregulation of mexX, a phenotype previously observed with other genetic lesions affecting ribosome function and that can be induced by the treatment with antibiotics affecting protein synthesis. [ABSTRACT FROM AUTHOR]

The aqueous environmental fate of two antibiotics, lincomycin and clarithromycin, and an antiepileptic drug, carbamazepine, was investigated by monitoring drugs decomposition and identifying intermediates in Po river water (North Italy). Initially, control experiments in the dark and under illumination were performed on river water spiked with drugs to simulate all possible transformation processes occurring in the aquatic system. Under illumination, these pharmaceuticals were degraded and transformed into numerous organic intermediate compounds. Several species were formed and characterised by analysing MS and MS spectra and by comparison with parent molecule fragmentation pathways. River water was sampled at three sampling points in an urban area. The selected pharmaceuticals were detected in all samples. Eight transformation products identified in the laboratory simulation were found in natural river water from carbamazepine degradation, three from clarithromycin and two from lincomycin. Their transformation occurring in aquatic system mainly involved mono- and poly-hydroxylation followed by oxidation of the hydroxyl groups. [ABSTRACT FROM AUTHOR]

Plants use light to fix carbon through the process of photosynthesis but light also causes photoinhibition, by damaging photosystem II (PSII). Plants can usually adjust their rate of PSII repair to equal the rate of damage, but under stress conditions or supersaturating light-intensities damage may exceed the rate of repair. Light-induced chloroplast movements are one of the many mechanisms plants have evolved to minimize photoinhibition. We found that chloroplast movements achieve a measure of photoprotection to PSII by altering the distribution of photoinhibition through depth in leaves. When chloroplasts are in the low-light accumulation arrangement a greater proportion of PSII damage occurs near the illuminated surface than for leaves where the chloroplasts are in the high-light avoidance arrangement. According to our findings chloroplast movements can increase the overall efficiency of leaf photosynthesis in at least two ways. The movements alter light profiles within leaves to maximize photosynthetic output and at the same time redistribute PSII damage throughout the leaf to reduce the amount of inhibition received by individual chloroplasts and prevent a decrease in photosynthetic potential. [ABSTRACT FROM AUTHOR]

In Japan, Lactococcus garvieae infection has been the main fish disease in aquaculture. Although commercial oral and injectable vaccines have been used to prevent L. garvieae infection in Japan, L. garvieae has been isolated not only from unvaccinated fish but also from vaccinated fish in which immunity induced by vaccination had diminished. In order to obtain epidemiological information on this fish pathogen, we conducted biased sinusoidal field gel electrophoresis (BSFGE) pattern analysis and phage typing of L. garvieae isolates ( n = 427) from fish in Japan. These isolates were obtained from 13 different fish species between 1980 and 2007. In the BSFGE analysis, L. garvieae isolates were classified into 17 groups (S1-S17) based on the SmaI digestion patterns and into four groups (A1-A4) based on the ApaI digestion patterns. Phage typing revealed five different phage susceptibility profiles (A-E) in L. garvieae isolates. Since 2005, comparisons of the results of phage typing and BSFGE have indicated the presence of a novel genotype (S16/A4) with phage type E. All the strains belonging to this type showed lincomycin sensitivity. [ABSTRACT FROM AUTHOR]

A sensitive and high selective chemiluminescence (CL) method was developed for the determination of lincomycin in acid medium using diperiodatonickelate as a reagent. The mechanism leading to luminescence is discussed by comparing the spectra of fluorescence and CL. Relative CL intensity is linear in the range from 8.0 ng mL−1 to 1.0 µg mL−1, the limit of detection is 2.5 ng mL−1 (3σ), and the relative standard deviation is 4.0% at 0.1 µg mL−1 of lincomycin ( n = 7). The method was successfully applied to the determination of lincomycin in injections, human urine, and in serum samples. [ABSTRACT FROM AUTHOR]

Antimicrobials administered to livestock can be excreted up to 75% in the feces and urine. Liquid swine manure from confined animal feeding operations is generally retained in lagoon storage until it is applied as a nutrient source to crop and pasture land. Thus, the applied manure becomes a possible source of antimicrobials to aquatic ecosystems. In the prairie region of Canada, lincomycin and spectinomycin are two antimicrobials that are frequently administered to pigs for prevention of post-weaning diarrhea. In order to assess the potential for contamination of prairie wetlands, concentrations of both antimicrobials were monitored in liquid manure from a commercial-scale barn during a 5-week study, and their persistence during simulated manure storage was investigated. LC-MS/MS analysis of manure extracts showed that concentrations of lincomycin and spectinomycin in the accumulating liquid manure at the end of the study were equivalent to 32 and 3%, respectively, of the doses administered to weanling pigs in their feed. In a laboratory study in which lagoon storage was simulated at room temperature using fortified liquid manure, concentrations of both antimicrobials showed a rapid initial decrease during the first 6 days, followed by a much slower dissipation, over a period of 5 months. Such persistence indicates that lincomycin and spectinomycin may be present in lagoon manure when applied as an amendment to agricultural land since many lagoons are emptied every 6 months (early spring and late fall). [ABSTRACT FROM AUTHOR]

The occurrence of pharmaceutically active chemicals (PACs) in the natural aquatic environment is recognized as an emerging issue due to the potential adverse effects these compounds pose to aquatic life and humans. This study presents the monitoring of two major categories of PACs in surface water: steroid hormones and antibiotics. Surface water samples were collected in the fall season from 21 locations in suburban (4), agricultural (5) and mixed (12) use suburban and agricultural areas. The water samples collected were analyzed using GC/MS for aqueous concentration of eleven steroid hormones: six natural (17 α-estradiol, 17β-estradiol, estrone, estriol, 17 α-dihydroequilin, progesterone) and five synthetic (gestodene, norgestrel, levonorgestrel, medrogestone, trimegestone). In addition, 12 antibiotics (oxytetracycline, chlorotetracycline, tetracycline, sulfamethoxazole, sulfamethazine, trimethoprim, lincomycin, norfloxacin, ofloxacin, roxithromycin, erythromycin, tylosin tartrate) were analyzed using LC/MS. Steroid hormones detected in surface water were: 17 α-estradiol, 17β-estradiol, 17 α-dihydroequilin, estriol, estrone, progesterone and trimegestone. Estrone had the highest detection frequency of >90% with concentrations ranging from 0.6 to 2.6 ng/l. The second most frequently detected estrogen was estriol (>80%) with concentrations ranging from 0.8 to 19 ng/l. The detection frequency varied at different sampling locations. No antibiotics were detected in the 21 streams sampled. This study aims to give a better understanding on the presence, fate and transport of PACs derived from humans and animals. [ABSTRACT FROM AUTHOR]

Some properties concerning conjugal transmission of chromosomal genes for resistance to antibiotics lincomycin, spectinomycin, and erythromycin that occurs upon contact of cells, which carry a large plasmid p19, and p19 plasmid-free cells are considered in the soil strain Bacillus subtilis 19. Genes were transferred at different rates, depending on the order of their transfer. The transfer of chromosomal genes occurred irrespective of the transmission of self-transmissible autonomous conjugative plasmid p19. [ABSTRACT FROM AUTHOR]

The biosynthetic pathway of the clinically important antibiotic lincomycin is not known in details. The precise knowledge of the lincomycin biosynthesis is a prerequisite for generation of improved derivatives by means of combinatorial genetics. Methods allowing determination of the key intermediates are very important tools of the pathway investigation. Two new high-performance liquid chromatography methods with fluorescence detection for determination of lincomycin precursors in fermentation broth of Streptomyces lincolnensis and its lincomycin nonproducing mutants were developed. The first one enables simultaneous analysis of methylthiolincosamide (MTL) and N-demethyllincomycin (NDL), whereas the second one is suitable for 4-propyl- l-proline (PPL) assay. Both methods are based on the pre-column derivatization: MTL and NDL with 4-chloro-7-nitrobenzofurazan; PPL with o-phthaldialdehyde. The methods were validated with lower limit of quantification values of 2.50, 3.75, and 3.75 μg ml−1 for MTL, NDL, and PPL, respectively. The inter- and intra-day accuracies and precisions were all within 12%. Stability of oxidized and derivatized analytes was investigated. [ABSTRACT FROM AUTHOR]