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Bacteriophage (phage) therapy is an alternative to traditional antibiotic treatments that is particularly important for multidrug-resistant pathogens, such as Pseudomonas aeruginosa. Unfortunately, phage resistance commonly arises during treatment as bacteria evolve to survive phage predation. During in vitro phage treatment of a P. aeruginosa-type strain, we observed the emergence of phage-resistant mutants with brown pigmentation that was indicative of pyomelanin. As increased pyomelanin (due to hmgA gene mutation) was recently associated with enhanced resistance to hydrogen peroxide and persistence in experimental lung infection, we questioned if therapeutic phage applications could inadvertently select for hypervirulent populations. Pyomelanogenic phage-resistant mutants of P. aeruginosa PAO1 were selected for upon treatment with three distinct phages. Phage-resistant pyomelanogenic mutants did not possess increased survival of pyomelanogenic ΔhmgA in hydrogen peroxide. At the genomic level, large (~300 kb) deletions in the phage-resistant mutants resulted in the loss of ≥227 genes, many of which had roles in survival, virulence, and antibiotic resistance. Phage-resistant pyomelanogenic mutants were hypersusceptible to cationic peptides LL-37 and colistin and were more easily cleared in human whole blood, serum, and a murine infection model. Our findings suggest that hyperpigmented phage-resistant mutants that may arise during phage therapy are markedly less virulent than their predecessors due to large genomic deletions. Thus, their existence does not present a contraindication to using anti-pseudomonal phage therapy, especially considering that these mutants develop drug susceptibility to the familiar FDA-approved antibiotic, colistin.

Background: Pediatric neurological disorders include neurodegenerative diseases causing cognitive impairment and vision loss. They are one of the important causes of morbidity and mortality in children with diverse etiologies. Diagnosis is difficult despite genetic work, and a final diagnosis can be achieved in only 60% of cases. Case presentation: We explore three Indian cases of pediatric neurological diseases (with age presented at the clinic), viz. arthrogryposis (8 years), autism (18 months), and congenital bilateral cataract (3 years), by analyzing clinical exomes. In this work, we attempt to understand rare neurological disorders in an Indian pediatric cohort using exome studies. Conclusion: We used our benchmarked CONVEX pipeline for screening consensus variants, wherein EIF2B2 was found to be inherently pathogenic. We map the association of variants and genes and disease correlation to neuroleptic malignant syndrome, which matches the phenotype to the cases. [ABSTRACT FROM AUTHOR]

Approximately 40–50% of municipal solid waste is organic and causing biogenic malodor and infections, due to inefficient treatment methods. Biorefinery-based bioremediation and valorization is in vogue against these conventional strategies since it combines unit operations for better efficiency and productivity. Deriving inspiration, the proposed strategy puts together a unique and compatible combination of processes. This novel two-step valorization workflow involves the extraction of small molecules using organic solvents, and fermentation of resulting denatured residues (increased biodegradability or decreased recalcitrance) of reduced microbial load. The extraction step also doubles up as a sterilization event, with different solvents (petroleum ether, chloroform, ethyl methyl ketone and methanol) exhibiting varied efficiency, methanol and ethyl methyl ketone being the most effective. Different recalcitrant plant organic wastes resulting from four plants (Cocos nucifera , Allium cepa , Artocarpus hirsutus and Swietenia mahagoni) were used as feedstocks in the preliminary exploratory study using chosen pathogenic bacteria. Onion peel (Allium cepa) ethyl methyl ketone extract was chosen for further studies, as it inhibits Salmonella enterica , which is associated with infection and malodour (due to biogenic H2S) in wastewater. Further, fractionation of the extract yielded quercetin and its glycoside. The onion peel residue, after solvent extraction was fortified with peptone and essential minerals to promote the growth of Bacillus clausii. Fortified post-extraction residue supported the growth better than the pre-extraction residue. The residue resultant after solvent extraction was fermented with Bacillus clausii and with release of bioactive supernatants. The concentrated supernatant showed significant inhibition of Salmonella enterica and Shigella dysenteriae. Additionally, all the exudates showed considerable inhibition in H2S production, respectively. [ABSTRACT FROM AUTHOR]

Arsenic contamination of soil and water is a major environmental issue. Bioremediation through plant growth-promoting bacteria is viable, cost-effective, and sustainable. Along with arsenic removal, it also improves plant productivity under stressful conditions. A crucial aspect of such a strategy is the selection of bacterial inoculum. The described study demonstrates that the indigenous wastewater isolate, ASBTKP1, could be a promising candidate. Identified as Klebsiella pneumoniae, ASBTKP1 harbors genes associated with heavy metal and oxidative stress resistance, production of antimicrobial compounds and growth-promotion activity. The isolate efficiently accumulated 30 µg/g bacterial dry mass of arsenic. Tolerance toward arsenate and arsenite was 120 mM and 70 mM, respectively. Plant biomass content of Vigna radiata improved by 13% when grown in arsenic-free soil under laboratory conditions in the presence of the isolate. The increase became even more significant under the same conditions in the presence of arsenic, recording a 37% increase. The phylogenetic analysis assigned ASBT-KP1 to the clade of Klebsiella strains that promote plant growth. Similar results were also observed in Oryza sativa, employed to assess the ability of the strain to promote growth, in plants other than V. radiata. This study identifies a prospective candidate in ASBT-KP1 that could be employed as a plant growth-promoting rhizoinoculant in agricultural practices. [ABSTRACT FROM AUTHOR]

Tuberculosis caused by the obligate intracellular pathogen, Mycobacterium tuberculosis, is one among the prime causes of death worldwide. An urgent remedy against tuberculosis is of paramount importance in the current scenario. However, the complex nature of this appalling disease contributes to the limitations of existing medications. The quest for better treatment approaches is driving the research in the field of host epigenomics forward in context with tuberculosis. The interplay between various host epigenetic factors and the pathogen is under investigation. A comprehensive understanding of how Mycobacterium tuberculosis orchestrates such epigenetic factors and favors its survival within the host is in increasing demand. The modifications beneficial to the pathogen are reversible and possess the potential to be better targets for various therapeutic approaches. The mechanisms, including histone modifications, DNA methylation, and miRNA modification, are being explored for their impact on pathogenesis. In this article, we are deciphering the role of mycobacterial epigenetic regulators on various strategies like cytokine expression, macrophage polarization, autophagy, and apoptosis, along with a glimpse of the potential of host-directed therapies. [ABSTRACT FROM AUTHOR]

Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.