AUTHOR=Ngba Essebe Christelle , Visvikis Orane , Fines-Guyon Marguerite , Vergne Anne , Cattoir Vincent , Lecoustumier Alain , Lemichez Emmanuel , Sotto Albert , Lavigne Jean-Philippe , Dunyach-Remy Catherine 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00077

DOI=10.3389/fcimb.2017.00077

ISSN=2235-2988

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