The regulatory network of Salmonella biofilm formation: the role of CsgD on autoinducer-2 activity and expression of quorum-sensing-related genes in Salmonella Typhimurium
Aug 2026· Zeitschrift für Induktive Abstammungs- und Vererbungslehre· Vol 301· 0 citations· 57 references
Medicine
TL;DR
CsgD may act as an integrative regulatory node linking transcriptional control of biofilm formation with quorum-sensing signaling pathways in Salmonella, and changes in CsgD levels are associated with shifts in QS-linked sRNA expression and AI-2 signaling dynamics.
ABSTRACT Streptococcus mutans is considered the key contributor to human dental caries. The LuxS/AI-2 quorum‑sensing (QS) system in S. mutans plays a crucial role in the development of cariogenic oral biofilms. Many QS systems rely on regulation carried out by small RNAs (sRNAs) to achieve optimal performance. However, the identities and functions of sRNAs in S. mutans QS system are not well elucidated. Here, we identify two novel sRNAs named SmqsR2 and SmqsR4 (Streptococcus mutans quorum-sensing-related small RNA 2 and 4), which respond to luxS expression and support biofilm formation by mediating exopolysaccharides (EPS) synthesis. We showed that overexpression of SmqsR2 and SmqsR4 in S. mutans, respectively, resulted in declined growth rates, altered biofilm architecture, increased EPS production, and upregulated expression of gtfB/C/D genes. Transcriptome analysis revealed that several genes related to carbohydrate utilization were differentially expressed, with ccpA being markedly upregulated in both SmqsR2 and SmqsR4 overexpression strains. Specifically, SmqsRs promoted ccpA transcript, and CcpA triggered transcription of SmqsR2 and SmqsR4 via direct binding, thus forming a positive feedback loop. We speculate that SmqsRs augment LuxS-mediated biofilm matrix production, most likely through the activation of gtfB/C/D expression and the reprogramming of S. mutans central carbon metabolism by ccpA. In summary, we have confirmed that SmqsR2 and SmqsR4 function as supporting factors that maintain the optimal status of the LuxS/AI-2 system in S. mutans, which is important for cell growth, EPS synthesis, and biofilm formation. Hence, sRNA activity may represent a promising target to modulate S. mutans cariogenicity.
M. Mao, Yan-Jing Liang, Juxiu Chen et al.· Virulence· 0 citations
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
The data obtained allows suggesting that SsrS and CsrC small RNAs played an important role in regulation of the cell switching to formation of biofilms, and hexuronates can be used as modeling agents in clinical practice.
T. Bessonova, U. D. Kuznetsova, A. T. Magkaev et al.· Molecular Biology· 0 citations
The effect of 8-methoxypsoralen (8-MOP) activated by UVA (365 nm) on the expression of the oxidative stress genes soxS and katG and SOS response genes recA and colD in Escherichia coli biosensors was studied. The luxCDABE operon of the luminescent bacterium Photorhabdus luminescens is a reporter for the expression of these genes in biosensors. A statistical method of segmented regressions was used to analyze the dynamics of dose–response relationships. It was established that when irradiated with UVA, 8-MOP induces the formation of superoxide anion and peroxide in the cells of pSoxS-lux and pKatG-lux biosensors, respectively. At the same time, the dynamics of biosensor responses differed significantly, which indicates the activation sequence of the corresponding promoters. pRecA-lux and pColD-lux biosensors are activated under conditions of DNA damage; however, the latter has significantly higher sensitivity. As compared to the recA, soxS, and katG promoters, the colD(cda) promoter shows a wider sensitivity and pronounced effect of signal amplification.
E. Igonina, I. Hu, S. Abilev et al.· Russian Journal of Genetics· 0 citations
The Type VI secretion system (T6SS) is a key nanoweapon in Gram-negative bacteria that mediates microbial competition and pathogenesis via toxic effector delivery. Three functionally distinct T6SS clusters (H1-H3) are known in Pseudomonas aeruginosa, yet the broader evolutionary diversity and regulatory networks of T6SS in this pathogen remain poorly defined. Here, we identify Sfa4, a transcriptional regulator linked to a fourth T6SS (H4-T6SS) in clinical isolate LYSZa7. Sfa4 directly binds amrZ and H4-T6SS cluster to activate their transcription. AmrZ, in turn, directly regulates all four T6SS clusters. We further show that c-di-GMP receptor FleQ directly binds the promoters of all four T6SS clusters, revealing a direct regulatory link between c-di-GMP signaling and T6SS transcription. This regulation, together with Sfa4-mediated elevation of intracellular c-di-GMP levels, coordinately enhances H4-T6SS activity, biofilm formation, and virulence in A549 alveolar epithelial cells and Galleria mellonella models. Phylogenetic analysis shows Sfa4 homologs are present in Gram-negative bacteria, implying a potential T6SS-regulatory function. Collectively, our findings shed light on regulatory cascades and provide a mechanistic basis for understanding how clinically acquired T6SS clusters may be integrated into existing virulence networks.
Yizhou Zhang, T. Ye, Jie Deng et al.· International Journal of Bio...· 0 citations
Biofilm formation is a pivotal virulence trait in
Vibrio alginolyticus
, providing protection against antimicrobial agents and host defenses. However, the regulatory mechanisms governing biofilm development remain incompletely elucidated. This study uncovers a novel regulatory circuit in which the small RNA
vvrr1
governs biofilm formation and pathogenicity by modulating the transcriptional regulator LeuO, which in turn coordinates the VarS/VarA two‐component system and the downstream Csr cascade. We demonstrate that
vvrr1
post‐transcriptionally represses LeuO by targeting
leuO
mRNA and accelerating its decay. The interaction interface is evolutionarily conserved among pathogenic
Vibrio
species, highlighting its functional importance. Phenotypic analyses established LeuO as a positive regulator of both biofilm formation and virulence. Genome‐wide profiling of LeuO binding sites revealed its direct repression of
varS
, which encodes the sensor kinase of the VarS/VarA system. This repression initiates a regulatory cascade: Reduced VarS/VarA activity alleviates repression of the Csr sRNAs (
csrB
,
csrC
, and
csrD
), leading to sequestration of the global regulator CsrA and subsequent derepression of the quorum‐sensing regulator LuxO. This coordinated regulation ultimately modulates exopolysaccharide biosynthesis, shaping biofilm architecture and virulence. By employing an integrated approach combining molecular simulations, genetic manipulations, and high‐throughput sequencing, we define a multilayered regulatory network centered on the
vvrr1
–LeuO axis. Our findings provide mechanistic insight into the sophisticated control of biofilm‐mediated virulence in a major aquaculture pathogen and identify potential targets for anti‐biofilm strategies.
T. Pengsakul, Lei Wen, Lingmin Zhao et al.· Animal Research and One Heal...· 0 citations
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