Biology subjects

Sawant, A. R.

Publications and source records attributed to Sawant, A. R..

3 recordsLinked to original sources

bioRxiv2026

Placentrex disrupts the biofilm formation of Pseudomonas aeruginosa through multi-target transcriptional reprogramming.

AimsPseudomonas aeruginosa biofilm-associated infections pose a significant clinical challenge due to their inherent antibiotic tolerance. This study aimed to evaluate the antibacterial and antibiofilm activity of Placentrex, a standardised aqueous placental extract, against P. aeruginosa and to elucidate its molecular mechanism of action using RNA sequencing (RNA-seq). Methods and ResultsPlacentrex exhibited potent bactericidal activity against P. aeruginosa at 50 {micro}g/mL. Biofilm formation was significantly inhibited by [~]87% at 50 {micro}g/mL after 72 hours. Preformed biofilms were eradicated by [~]93% and [~]89% at 50 and 25 {micro}g/mL, respectively. Interestingly, biofilm viability was reduced by [~]93% and [~]87% upon treatment with 50 {micro}g/mL and 25 {micro}g/mL of Placentrex, respectively. EPS characterisation revealed that the EPS contain a single large polysaccharide, and chromatography data suggested that it is made up of glucose as a monomer. RNA-seq identified coordinated downregulation of seven key genes, namely, flp major pilin (surface attachment), extracellular solute binding protein (ABC transporter-mediated nutrient sensing and biofilm maintenance), gntP permease (carbon metabolism), AraC family transcriptional regulator (quorum sensing and polysaccharide biosynthesis), ureE (urease nickel metallochaperone), aromatic amino acid permease (pyoverdine and PQS biosynthesis), and MFS transporter (efflux and autoinducer export). ConclusionsPlacentrex exerts comprehensive antibiofilm and antibacterial activity through simultaneous disruption of surface attachment, nutrient-sensing-driven biofilm maintenance, quorum sensing, carbon metabolism, urease virulence maturation, and efflux-mediated persistence. This polypharmacological mechanism supports Placentrex as a promising multi-target antibacterial agent against P. aeruginosa biofilm-associated infections. Impact statementPlacentrex is a potential anti-biofilm agent against Pseudomonas aeruginosa.

microbiology↗

bioRxiv2025

Putative MFS transporter Rv1250 of Mycobacterium tuberculosis is involved in multidrug efflux activity

Drug-resistant Mycobacterium tuberculosis is one of the leading causes of global mortality. Mechanisms, such as slow uptake of drugs along with cell wall impermeability and active efflux, are some of the concerning reasons leading to drug resistance. Efflux pumps actively transport a wide variety of drugs and toxins away from the target site, which is considered an emerging cause for the failure of anti-tubercular medications and treatment. In this study, we report that the ability of Rv1250, a probable MFS-type transporter, influences the extrusion of multiple structurally unrelated classes of drugs, enhances the biofilm formation in E. coli and Mycobacterium smegmatis, and facilitates the survival of M. smegmatis cells inside the macrophage during antibiotic stress. Interestingly, in trans, the expression of rv1250 decreased the susceptibility of host cells to several structurally unrelated antibiotics, ranging from fluoroquinolones to aminoglycosides, beta-lactams, and anti-tubercular drugs, thus indicating its involvement in imparting intrinsic drug tolerance. In addition, the increased efflux of EtBr, norfloxacin, and Bocillin FL from host cells expressing rv1250 was revealed by the hosts ability to confer a lower level of antibiotic accumulation. Moreover, the expression of rv1250 resulted in the enhancement of biofilm formation. Overall, we conclude that Rv1250 of Mycobacterium tuberculosis might facilitate the survival of host cells under antimicrobial stress. One sentence summaryRole of Rv1250 as an efflux pump

microbiology↗

bioRxiv2025

Deletion of major shell protein of ethanolamine utilization microcompartment reduces intrinsic antibiotic resistance, biofilm and intracellular survival of Salmonella Typhimurium

With the high rise in Salmonella infection and emergence of antibiotic-resistant variants, developing a novel strategy to control the pathogen is imperative. Earlier studies revealed that Salmonella deploys ethanolamine (EA) metabolic machinery to disseminate in the intestine. Salmonella with a defect in EA metabolism manifests with lower intestinal colonization efficiency. Remarkably, the potential of EA metabolism as a therapeutic target is yet to explore. Our study revealed that supplementation of EA and vitamin B12 in both rich and minimal media enhanced biofilm formation, increased motility, and increased tolerance of Salmonella to some antibiotics. Conversely, mutants deficient in EA metabolic enzymes exhibited no physiological fitness. In Salmonella, EA metabolic enzymes are localized within a proteinaceous microcompartment (MCP) shell composed of thousands of copies of shell proteins encoded by five genes from the eut operon. Fascinatingly, bacterial cells with defective MCP shell due to mutation in the major shell proteins showed enhanced susceptibility towards a number of antibiotics in minimal media. The mutants were unable to form biofilm, produced lower curli expression and were defective in flagellar motility. Also, mutation in one of the major shell proteins reduced intramacrophagic viability of Salmonella. Notably, phenotypes were restored upon ectopic expression of corresponding genes. It was evident that mutation in the MCP shell proteins downregulated the expression of genes related to pathogenicity. Overall, this study sheds new light on understanding the relationship between EA metabolism and bacterial physiology that would pave the way for developing novel therapeutic interventions against Salmonella.

microbiology↗