Caenorhabditis elegans as a host model for community-associated methicillin-resistant Staphylococcus aureus

Abstract

The nematode Caenorhabditis elegans has recently been developed as a host model for the study of Staphylococcus aureus virulence and pathogenesis. Here, the toxicity and virulence of representative clinical isolates of our methicillin-resistant S. aureus (MRSA) epidemic strains were studied using this model. The strains USA300 (associated with community infection outbreaks), USA400 (associated with sporadic community infections) and CMRSA2 (associated with both hospital and community infections), as well as the nematocidal reference strain NCTC8325, showed high nematocidal activity, both by killing the majority of the nematodes (> 90%) over 9 days, and by inhibiting second-generation nematode growth. By contrast, the typical hospital-associated MRSA strain CMRSA6, the colonization strain M92, and the non-pathogenic Staphylococcus epidermidis control strain ATCC12228 were non-toxic to the nematode, which behaved normally. The absence of nematocidal activity does not reflect lack of growth or reduced growth of the bacterial inoculum. The two non-nematocidal strains share similar genomic backgrounds, bacterial growth curve patterns and virulence gene profiles. However, the nematocidal strains each showed the same low maximum density growth curve patterns, but possessed distinct genetic profiles; no common virulence gene patterns or specific genes have been elucidated. Our findings demonstrate that community-associated MRSA strains are more pathogenic than hospital-associated MRSA in the C. elegans model and support the use of this model for studying the virulence of S. aureus strains.

Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

“…The methicillin-susceptible S. aureus strain NCTC8325-4 [19] and methicillin-resistant S. aureus (MRSA) strain ATCC33591 were grown with aeration in Trypticase Soy (TS) media (Oxoid/Pronadisa) at 37°C while Escherichia coli strain OP50 was grown in Luria Bertani (LB) broth supplemented with streptomycin (100 μg/mL). The wild type C. elegans Bristol N2 hermaphrodite strain was propagated on nematode growth medium (NGM) and fed on the standard laboratory food source, E. coli OP50.…”

“…Infection of C. elegans by S. aureus is a robust platform to elucidate the mechanisms of host-pathogen interaction [19-22]. In this study, our aim was to extend these studies to the discovery of novel anti-infectives.…”

Complete Genome Sequence of the Methicillin-Resistant Staphylococcus aureus Colonizing Strain M92

“…The staphylococcal protein A gene ( spa ) is truncated in M92. It has been used as an avirulence control strain in many of our infection models (4–6). We sequenced the complete genome of M92, in order to compare it to those highly virulent MRSA strains to give a more complete understanding of MRSA virulence factors.…”

Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation

“…There is growing appreciation that the nematode can serve as a powerful tool in drug discovery including identification of antifungal and antimicrobial compounds (Moy et al, 2006; Breger et al, 2007). To date, a wide and still expanding range of pathogens have been reported to infect C. elegans including the human pathogen S. aureus (Sifri et al, 2003; Wu et al, 2010; JebaMercy et al, 2011). S. aureus kills C. elegans via accumulation of large numbers of live bacteria within the intestinal tract (Sifri et al, 2003; Irazoqui et al, 2010) and several virulence determinants known to be important in mammalian pathogenesis are also required for full pathogenicity against nematodes (Sifri et al, 2003).…”