Aug 2026· Microbial Pathogenesis· pp.
108790
· 0 citations· 21 references
Medicine
TL;DR
This study provides a theoretical basis for elucidating the molecular mechanism by which YibT modulates salmonella pathogenicity and shows that yibT contributes to regulate adhesion and invasion of S. typhimurium, and its deletion attenuates bacterial virulence and host pathogenicity.
Abstract
Salmonella typhimurium, a Gram-negative pathogen widely distributed in the environment, poses a serious threat to public health by contaminating food and causing foodborne diseases. Our preliminary study found that under thymol stress, the expression of YibT, a poorly characterized factor in salmonella, was significantly reduced, and deletion of the yibT gene markedly impaired biofilm formation. However, the biological role of yibT in salmonella pathogenesis remains unclear. In this study, the λ-Red homologous recombination system and pET28a vector were used to construct the single deletion mutant STΔrpoS, the double deletion mutant STΔrpoSΔyibT, complementation strains, and an overexpression strain. Promoter reporter vectors were constructed using pKP302. Growth characteristics, biofilm formation, adhesion, invasion, virulence, and pathogenicity were evaluated. The regulatory relationship between rpoS and yibT was examined by β-galactosidase assays. Results showed that deletion of rpoS and yibT led to slow growth, reduced biofilm formation, and decreased flagella and surface appendages under transmission electron microscopy. qRT-PCRshowed that there is a negative feedback loop between yibT and rpoS, where RpoS positively regulates yibT transcription and YibT negatively regulates RpoS expression. Preliminary detection of β-galactosidase confirms that yibT may be located downstream of rpoS. Cellular infection models demonstrated that deletion of yibT and rpoS significantly reduced salmonella adhesion, invasion, and intracellular survival. In mouse infection experiments, bacterial loads in the liver, spleen, and ileum were markedly decreased in mutant-infected mice, with further reduction under quercetin intervention. Flow cytometry analysis of T-cell subsets suggested attenuated immune modulation by the mutant strains, indicating reduced pathogenicity. Collectively, yibT contributes to regulate adhesion and invasion of S. typhimurium, and its deletion attenuates bacterial virulence and host pathogenicity. YibT may participate in the virulence regulatory network by interacting with the transcriptional regulator RpoS. This study provides a theoretical basis for elucidating the molecular mechanism by which YibT modulates salmonella pathogenicity.
Biofilm formation is a fundamental survival strategy that enables bacterial persistence across diverse environments and hosts. While the mrk gene cluster encoding type 3 fimbriae is a well-established determinant of biofilm formation in Klebsiella pneumoniae, its presence and functional significance in Salmonella enterica remains poorly defined. In this study, we identified a plasmid-encoded mrkABCDF gene cluster carried on a highly conjugative IncX1 plasmid in a clinical Salmonella Thompson isolate. Using CRISPR/Cas9-mediated knockout of the mrk-containing Tn6011 transposon, plasmid curing, targeted gene deletion, and genetic complementation, we systematically dissected the contribution of mrkABCDF genes to biofilm development and associated phenotypes. Loss of the mrk gene cluster resulted in a profound reduction in biofilm biomass and a concomitant increase in bacterial motility. Type 3 fimbriae were detected exclusively on the surface of mrk-positive cells, confirming their structural role in surface attachment. The mrk operon was strongly expressed from an IS1-associated promoter, bypassing canonical MrkH-dependent regulation. Functionally, mrk expression enhanced bacterial tolerance to desiccation and oxidative stresses, and reduced susceptibility to macrophage phagocytosis. In vivo, mrk-positive strains exhibited enhanced gastrointestinal colonization and tissue invasion. Notably, carbapenems exhibited exceptional efficacy in inhibiting mrk-mediated biofilm formation, indicating their superior potential for treating biofilm-associated infections. Our findings demonstrate that plasmid-encoded mrkABCDF genes can act as key architectural and functional determinants of biofilm formation in Salmonella enterica. The horizontal dissemination of mrk-carrying IncX1 plasmids may promote the emergence of biofilm-adapted Salmonella lineages with enhanced environmental persistence and host colonization potential.
Ke Liu, Liya Feng, Lu Ouyang et al.· Biofilm· 0 citations
YgeP plays a central role in APEC pathogenesis by balancing two infection strategies: motility-mediated dissemination and colonization, and biofilm-mediated attachment and tolerance, and negatively regulates key virulence traits during the early stages of infection.
Weiyang Su, Zhe Li, Siqi Feng et al.· Veterinary Microbiology· 0 citations
Background Salmonella enterica serovar Enteritidis (S. Enteritidis) is a leading global cause of foodborne illnesses. The emergence of multidrug-resistant strains has exacerbated clinical treatment challenges and public health threats. The tricarboxylic acid (TCA) cycle is central to bacterial carbon metabolism, with key enzyme-encoding genes linked to environmental adaptation and pathogenicity. However, the biological role of ΔgltA, which encodes citrate synthase, the rate-limiting enzyme initiating the TCA cycle, in S. Enteritidis, and its potential as an attenuated vaccine target remain poorly understood. Methods We constructed a gltA deletion mutant (ΔgltA) and its complemented strain (ΔgltA+gltA) from S. Enteritidis C50336of using λ-Red homologous recombination. We systematically characterized the effects of ΔgltA deletion on bacterial growth, antimicrobial susceptibility, and stress tolerance. Transcriptomics and qRT-PCR were employed to investigate virulence regulation mechanisms, while mouse models were used to evaluate attenuation and immunoprotective efficacy. Results ΔgltA deletion did not alter growth in nutrient-rich LB or nutrient-poor M9 media, but significantly impaired motility and biofilm formation by inhibiting curli fimbriae and cellulose synthesis, and increased susceptibility to 15 antimicrobial agents. The ΔgltA mutant also showed reduced tolerance to acidic, alkaline, oxidative, thermal, and osmotic stresses. Notably, intraperitoneal infection revealed >106-fold attenuation in Kunming mice (wild-type LD50 = 3.16 × 10³ CFU; no mortality at 1 × 109 CFU ΔgltA), with decreased organ bacterial loads and global downregulation of 24 key virulence genes. A single oral immunization with ΔgltA elicited robust humoral and cellular immunity, conferring promising protection against lethal wild-type challenge. Conclusion Deletion of ΔgltA is associated with altered metabolic homeostasis, impaired environmental adaptability and attenuated pathogenicity in S. Enteritidis. The ΔgltA mutant conferred effective protective immunity in the mouse model used here, serving as a promising candidate strain and molecular target for further development of live attenuated S. Enteritidis vaccines.
Siping Zhu, Miao Wang, Xintong Zhu et al.· Frontiers in Immunology· 0 citations
Transcriptional analysis revealed that compared to neutral conditions, osmotic stress-related genes were significantly upregulated in the ΔliaS strain under acidic conditions, indicating that LiaS modulates acid tolerance through transcriptional regulation.
Yong-Shu Wu, Jiali Xu, Yifan Wang et al.· Virulence· 0 citations
The dynamic expression of UPEC's stress response mechanisms are emphasized and the central role of Bar/UvrY in modulating pathoadaptive mechanisms under antibiotic stress is outlined.
Ali Hazim Jabbar, M. Flayyih· Iraqi Journal of Science· 0 citations
It is indicated that relA plays a key role in APEC virulence, antibiotic resistance, and membrane homeostasis, and could provide a theoretical basis for targeting the stringent response as a potential strategy to control avian colibacillosis.
Jiangang Hu, Dossêh Jean Apôtre Afayibo, Chang Liu et al.· Microorganisms· 0 citations
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