Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, China.
Appl Environ Microbiol. 2024 Oct 23;90(10):e0156424. doi: 10.1128/aem.01564-24. Epub 2024 Sep 19.
poses a significant threat, particularly to neonates and infants. Despite its strong pathogenicity, understanding of biofilms and their role in infections remains limited. This study investigates the roles of HmsP and c-di-GMP in biofilm formation and identifies key genetic and proteomic elements involved. Gene knockout experiments reveal that HmsP and c-di-GMP are linked to biofilm formation in . Comparative proteomic profiling identifies the lysozyme inhibitor protein LprI, which is downregulated in knockouts and upregulated in c-di-GMP knockouts, as a potential biofilm formation factor. Further investigation of the knockout strain shows significantly reduced biofilm formation and decreased virulence in a rat infection model. Additionally, LprI is demonstrated to bind extracellular DNA, suggesting a role in anchoring within the biofilm matrix. These findings enhance our understanding of the molecular mechanisms underlying biofilm formation and virulence in , offering potential targets for therapeutic intervention and food production settings.IMPORTANCE is a bacterium that poses a severe threat to neonates and infants. This research elucidates the role of the lysozyme inhibitor LprI, modulated by HmsP and c-di-GMP, and uncovers a key factor in biofilm formation and virulence. The findings offer crucial insights into the molecular interactions that enable to form resilient biofilms and persist in hostile environments, such as those found in food production facilities. These insights not only enhance our understanding of pathogenesis but also identify potential targets for novel therapeutic interventions to prevent or mitigate infections. This work is particularly relevant to public health and the food industry, where controlling contamination in powdered infant formula is vital for safeguarding vulnerable populations.
对新生儿和婴儿构成重大威胁。尽管其具有很强的致病性，但对生物膜及其在感染中的作用的理解仍然有限。本研究调查了 HmsP 和 c-di-GMP 在生物膜形成中的作用，并确定了涉及的关键遗传和蛋白质组学元素。基因敲除实验表明，HmsP 和 c-di-GMP 与 生物膜形成有关。比较蛋白质组学分析鉴定出溶菌酶抑制剂蛋白 LprI，其在 敲除体中下调，在 c-di-GMP 敲除体中上调，是潜在的生物膜形成因子。对 敲除株的进一步研究表明，其生物膜形成显著减少，在大鼠感染模型中的毒力降低。此外，LprI 被证明与细胞外 DNA 结合，表明其在将 锚定在生物膜基质中的作用。这些发现增强了我们对 生物膜形成和毒力的分子机制的理解，为治疗干预和食品生产环境提供了潜在的靶点。重要的是一种对新生儿和婴儿构成严重威胁的细菌。本研究阐明了受 HmsP 和 c-di-GMP 调节的溶菌酶抑制剂 LprI 的作用，并揭示了生物膜形成和毒力的关键因素。这些发现为 形成弹性生物膜并在敌对环境中存活的分子相互作用提供了重要的见解，这些环境在食品生产设施中很常见。这些见解不仅增强了我们对 发病机制的理解，还确定了潜在的治疗干预靶点，以预防或减轻感染。这项工作与公共卫生和食品工业特别相关，因为控制婴儿配方奶粉中的 污染对于保护弱势群体至关重要。
