Department of Microbiology and Hospital Hygiene, CHU Nîmes, VBIC, INSERM U1047, Univ Montpellier, Nîmes, France.
Département Médicaments et Technologies pour la Santé (DMTS), Université Paris-Saclay, CEA, INRAE, Bagnols-sur-Cèze, SPI, France.
BMC Microbiol. 2024 Oct 11;24(1):406. doi: 10.1186/s12866-024-03520-0.
Staphylococcus aureus is the predominant pathogen isolated in diabetic foot infections. Recently, the skin commensal bacterium, Helcococcus kunzii, was found to modulate the virulence of this pathogen in an in vivo model. This study aims to elucidate the molecular mechanisms underlying the interaction between these two bacterial species, using a proteomic approach.
Our results reveal that H. kunzii can coexist and proliferate alongside S. aureus in a Chronic Wound Media (CWM), thereby mimicking an in vitro chronic wound environment. We noted that the secreted proteome of H. kunzii induced a transcriptional effect on S. aureus virulence, resulting in a decrease in the expression level of agrA, a gene involved in quorum sensing. The observed effect could be ascribed to specific proteins secreted by H. kunzii including polysaccharide deacetylase, peptidoglycan DD-metalloendopeptidase, glyceraldehyde-3-phosphate dehydrogenase, trypsin-like peptidase, and an extracellular solute-binding protein. These proteins potentially interact with the agr system, influencing S. aureus virulence. Additionally, the virulence of S. aureus was notably affected by modifications in iron-related pathways and components of cell wall architecture in the presence of H. kunzii. Furthermore, the overall metabolism of S. aureus was reduced when cocultured with H. kunzii.
Future research will focus on elucidating the role of these excreted factors in modulating virulence.
金黄色葡萄球菌是糖尿病足感染中分离出的主要病原体。最近,发现皮肤共生菌 Helcococcus kunzii 可以在体内模型中调节这种病原体的毒力。本研究旨在使用蛋白质组学方法阐明这两种细菌相互作用的分子机制。
我们的结果表明,H. kunzii 可以在慢性伤口培养基 (CWM) 中与 S. aureus 共存和增殖,从而模拟体外慢性伤口环境。我们注意到,H. kunzii 的分泌蛋白质组对 S. aureus 毒力产生了转录效应,导致参与群体感应的 agrA 基因的表达水平降低。观察到的效应可归因于 H. kunzii 分泌的特定蛋白质,包括多糖脱乙酰酶、肽聚糖 DD-金属内肽酶、甘油醛-3-磷酸脱氢酶、胰蛋白酶样肽酶和细胞外溶质结合蛋白。这些蛋白质可能与 agr 系统相互作用,影响 S. aureus 的毒力。此外,当与 H. kunzii 共培养时,金黄色葡萄球菌的毒力明显受到铁相关途径和细胞壁结构成分的修饰的影响。此外,当与 H. kunzii 共培养时,S. aureus 的整体代谢减少。
未来的研究将集中阐明这些分泌因子在调节毒力方面的作用。