Interactions between Helcococcus kunzii and Staphylococcus aureus: How a commensal bacterium modulates the virulence and metabolism of a pathogen in a chronic wound in vitro model

Abstract

Background 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. Results Our results demonstrate that H. kunzii can coexist and grow with S. aureus in a Chronic Wound Media (CWM), mimicking an in vitro chronic wound environment. We observed that the secreted proteome of H. kunzii induced a transcriptional effect on S. aureus virulence, leading to a decrease in the expression level of agrA, a gene involved in quorum sensing. The observed effect may be attributed 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, affecting S. aureus virulence. Additionally, the virulence of S. aureus was notably impacted by alterations 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. Conclusion Future investigations will focus on elucidating the role of these excreted factors in modulating virulence.