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Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications.  Staphylococcus aureus  is the most prevalent pathogen isolated. Its association with  Helcococcus kunzii , commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both  H. kunzii  and  S. aureus  strains in a  Caenorhabditis elegans  model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that  H. kunzii  strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast,  S. aureus  strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all  H. kunzii  ( P  < 0.001). When  H. kunzii  and  S. aureus  strains were associated,  H. kunzii  significantly reduced the virulence of the  S. aureus  strain in nematodes (LT50 between 4.4 and 5.2 days;  P  < 0.001). To evaluate the impact of these strains on host response, transcriptomic analysis showed that the ingestion of  S. aureus  led to a strong induction of defense genes ( lys-5, sodh-1 , and  cyp-37B1 ) while  H. kunzii  did not. No statistical difference of host response genes expression was observed when  C. elegans  were infected with either  S. aureus  alone or with  S. aureus  +  H. kunzii . Moreover, two well-characterized virulence factors ( hla  and  agr ) present in  S. aureus  were down-regulated when  S. aureus  were co-infected with  H. kunzii . This study showed that  H. kunzii  decreased the virulence of  S. aureus  without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated.

Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model