Stage V sporulation protein G as a global regulator of biofilm formation and virulence in Staphylococcus species: molecular mechanisms and therapeutic potential
Jul 2026· World Journal of Microbiology & Biotechnology· Vol 42· 0 citations· 72 references
Medicine
TL;DR
This review highlights SpoVG’s function in Staphylococcus, including its regulation of the expression of the adhesion factor gene sasC and the thermonuclease, which enables SpoVG to act as a molecular rheostat that influences biofilm formation and reduces acute virulence in response to environmental signals.
The Quorum Sensing (QS) system plays a central role in regulating several processes that influence bacterial physiology, communication, and pathogenesis. It governs the production of virulence factors, facilitates biofilm formation, and contributes to the development of antibiotic resistance, all of which are critical to bacterial survival and pathogenicity. QS enables both intraspecies and inter-species bacterial communication, operating through distinct pathways in Gram-positive and Gram-negative bacteria. This review provides a comprehensive overview of the major families of quorum-sensing proteins involved in the working of the signalling molecules. It examines the structural features, functional roles, and mechanisms of action of these proteins, highlighting their significance in bacterial behaviour. Furthermore, the study explores the potential of plant-derived secondary metabolites as natural inhibitors targeting QS systems to disrupt bacterial pathogenicity. Finally, it discusses the implications of exploiting these inhibitors as promising strategies to address the growing challenge of antibiotic resistance in bacterial infections.
Asghar Ali, Andaleeb Zahra, Mohan Kamthan et al.· Current Topics in Medicinal...· 0 citations
Background: Staphylococcus aureus causes bloodstream and skin infections in humans. The prevalence of multidrug-resistant S. aureus strains means new antibiotics are needed. A novel antimicrobial drug named SK-03-92, a synthetic aromatic organic stilbenoid compound, kills S. aureus cells within 30 min, but an increase in both biofilm formation and persister cells occurs. SK-03-92 treatment downregulates transcription of the biofilm regulating protein regulator (brpR) gene and biofilm regulating protein sensor (brpS) gene in S. aureus. BrpR/BrpS system may be a LytTR regulatory system tied to biofilm formation, creation of persister cells, and late-stage competence in S. aureus. The aim of this study was to determine what biofilm, late-stage competence, and persister-associated genes were regulated in a brpR mutant compared to wild-type strains. Methods: In this study, involvement of BrpR in regulating other genes was assessed by comparing transcriptional changes in a brpR mutant strain to the S. aureus parent strain via RNA sequencing (RNA-Seq). Bioinformatic analysis was then performed on the RNA-Seq data to assess what biochemical pathways might be involved. Results: From these analyses, 440 genes were identified that had significant differences in transcript abundance when comparing the brpR mutant to wild-type strains. Quantitative reverse transcription polymerase chain reaction analysis confirmed bacA, icd, metE, and pdhA transcript levels were lower, whereas alr and mraY were higher in the brpR mutant versus wild-type strain. Furthermore, an enzymatic assay targeting NADH production from the pyruvate dehydrogenase complex showed lower levels in the mutant compared to wild-type strain. Conclusions: Overall, the study demonstrated several biosynthetic pathways tied to biofilm formation and late-stage competency may be regulated by BrpR and some potential leads for the mechanism of action of the SK-03-92 drug were uncovered.
Hailey Dyce, P. Schweiger, Robin Patel et al.· Antibiotics· 0 citations
Stenotrophomonas maltophilia is increasingly recognized as a difficult-to-treat healthcare-associated opportunistic pathogen, particularly in critically ill and immunocompromised patients, in whom it causes severe respiratory, bloodstream, and device-associated infections. Its intrinsic resistance to multiple antimicrobial classes, capacity to acquire additional resistance determinants, and ability to establish persistent biofilms substantially limit therapeutic options. This review integrates current knowledge of the structural basis, regulatory circuitry, and ecological interactions governing S. maltophilia biofilm development and examines how these processes converge with antimicrobial resistance. Biofilm formation is driven by coordinated adhesion and motility, extracellular matrix production, quorum sensing, cyclic di-GMP signaling, two-component regulatory systems, and adaptive responses to iron limitation and oxidative stress. Multidrug efflux systems contribute not only to antibiotic extrusion but also to membrane homeostasis, motility, stress adaptation, and biofilm-associated phenotypes, thereby providing a functional link between antimicrobial resistance and bacterial persistence. In polymicrobial communities, interspecies signaling and competitive or cooperative interactions further reshape biofilm architecture and antimicrobial tolerance. Collectively, current evidence indicates that S. maltophilia biofilm formation arises from interconnected regulatory networks rather than isolated molecular determinants. Targeting matrix assembly, signaling pathways, stress adaptation, or resistance-associated physiology may therefore complement conventional antimicrobial therapy. Future studies should prioritize clinically representative isolates, physiologically relevant multispecies models, and in vivo validation to translate mechanistic insights into effective anti-biofilm interventions.
How nutrient stress shapes bacterial evolution and the associated fitness trade-offs remains a central question in microbiology. Using Burkholderia thailandensis as a surrogate for the pathogen B. pseudomallei, we performed adaptive laboratory evolution with casein as the sole carbon source. Over 30 days of serial passaging, the population shifted towards protease deficiency, with mutants constituting 54.94% by the endpoint. These evolved strains exhibited pleiotropic virulence attenuation-including reduced rhamnolipid production, motility, auto-aggregation, and biofilm formation-alongside increased susceptibility to imipenem and chloramphenicol. RNA-seq analysis of evolved strain E3101 revealed 2,836 differentially expressed genes, with significant downregulation of quorum sensing (AHL synthesis), rhamnosyltransferases, flagellar assembly, and biofilm regulatory pathways. Our findings demonstrate that casein-driven evolution selects for social 'cheaters' that conserve energy by downregulating costly virulence determinants, revealing a fundamental virulence-fitness trade-off. The coordinated transcriptional repression of biofilm and antibiotic resistance pathways provides a mechanistic framework for understanding bacterial adaptation strategies and potential therapeutic vulnerabilities in Burkholderia.
The functional analysis revealed that the Δpimt mutant strain shows defective motility, reduced biofilm formation, and defective invasion and intramacrophage survival, and supplementation of Δpimt mutant strain culture with reduced glutathione resulted in neutralization of ROS and rescued the defective motility and biofilm formation of the mutant strain.
R. Mahindhan, T. K. Chauhan, Shikha Bishnoi et al.· International Journal of Bio...· 0 citations
ABSTRACT Antimicrobial resistance is a major global health threat, exacerbated by bacterial virulence mechanisms such as quorum sensing (QS) and biofilm formation, which enhance pathogenicity and reduce antibiotic susceptibility. Targeting QS offers a promising antivirulence strategy that may attenuate pathogenic traits without imposing selective pressure. In this study, lawsone was evaluated for anti-QS and antibiofilm activity against Chromobacterium violaceum, Pseudomonas aeruginosa, and Serratia marcescens. Lawsone significantly inhibited QS-regulated virulence factors, with reductions in violacein production in C. violaceum (90.62%) at 250 µg/mL (1.43 mM). There was also a reduction in pyocyanin and pyoverdin in P. aeruginosa (87.90% and 81.97%, respectively) and prodigiosin in S. marcescens (~83%) at 500 µg/mL (2.87 mM) lawsone. Additionally, lawsone suppressed protease and elastase activities, as well as rhamnolipid production in P. aeruginosa. Biofilm formation was inhibited in a dose-dependent manner, reaching 84.28% in C. violaceum, 76.22% in P. aeruginosa, and 56.27% in S. marcescens at respective sub-MICs. Computational analyses supported these findings; docking showed stable binding of lawsone to QS regulators, including CviR (−7.8 kcal/mol), LasR (−8.5 kcal/mol), and SmaR (−7.7 kcal/mol). Molecular dynamics simulations confirmed the stability of these complexes, with root mean square deviation values of 0.200 ± 0.016 nm (CviR-lawsone), 0.238 ± 0.036 nm (LasR-lawsone), and 0.632 ± 0.061 nm (SmaR-lawsone). Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) calculations further demonstrated favorable binding. To my knowledge, this is the first study to systematically demonstrate the anti-QS and antibiofilm potential of lawsone across multiple clinically relevant gram-negative pathogens using an integrated experimental and computational approach. This work provides possible mechanistic insights into lawsone-QS regulator interactions, highlighting its potential as a broad-spectrum antivirulence agent targeting conserved QS systems. IMPORTANCE Antimicrobial resistance is a growing global threat, driven in part by bacterial virulence mechanisms such as quorum sensing (QS) and biofilm formation. Targeting QS offers an alternative strategy to reduce pathogenicity without promoting resistance. This study shows that lawsone effectively inhibits QS-regulated virulence factors and biofilm formation in gram-negative pathogens, like Pseudomonas aeruginosa, Serratia marcescens, and Chromobacterium violaceum. These findings highlight lawsone as a promising antivirulence agent that could complement existing therapies for managing biofilm-associated and drug-resistant infections. Antimicrobial resistance is a growing global threat, driven in part by bacterial virulence mechanisms such as quorum sensing (QS) and biofilm formation. Targeting QS offers an alternative strategy to reduce pathogenicity without promoting resistance. This study shows that lawsone effectively inhibits QS-regulated virulence factors and biofilm formation in gram-negative pathogens, like Pseudomonas aeruginosa, Serratia marcescens, and Chromobacterium violaceum. These findings highlight lawsone as a promising antivirulence agent that could complement existing therapies for managing biofilm-associated and drug-resistant infections.
