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

Abstract

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.

Adaptation of Staphylococcus aureus in a Medium Mimicking a Diabetic Foot Environment

“…The C. elegans infection assay was performed as previously described using the Fer-15 mutant line, which has a temperature sensitive fertility defect [ 66 ]. Fer-15 was provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR).…”

“…Approximately 30 L4 animals were placed in the center of the bacteria lawn. The number of nematodes inside or outside each lawn was counted after 16 h, as previously described [ 66 ]. The results were described in percent occupancy corresponding to the number of C. elegans in the bacterial lawn/the total number of nematodes.…”

Biofilms in Diabetic Foot Ulcers: Significance and Clinical Relevance

“…Competition between commensal and pathogenic bacteria has been observed during cutaneous colonization [ 79 ]. In contrast, Helcococcus kunzii (a commensal Gram-positive coccus) and S. aureus cooperation led to a decrease of S. aureus virulence in Caenorhabditis elegans [ 80 ]. S. aureus shifts toward commensalism in response to Corynebacterium sp.…”

Pediococcus acidilactici P25 Protected Caenorhabditis elegans against Enterotoxigenic Escherichia coli K88 Infection and Transcriptomic Analysis of Its Potential Mechanisms

“…Due to the high homology of genes between nematodes and mammals and because nematodes have a relatively complete digestive system, C. elegans can be used as a host-pathogen interaction model in scientific research [58,59]. In this study, results demonstrated that nematodes treated with P25 had a…”