Virulence of Staphylococcus aureus small colony variants in the Caenorhabditis elegans infection model - PubMed (original) (raw)

Virulence of Staphylococcus aureus small colony variants in the Caenorhabditis elegans infection model

Costi D Sifri et al. Infect Immun. 2006 Feb.

Abstract

Small colony variants (SCVs) of Staphylococcus aureus are slow-growing morphological variants that have been implicated in persistent, relapsing, and antibiotic-resistant infections. The altered phenotype of SCVs in most strains has been attributed to defects in electron transport due to mutations in hemin or menadione biosynthesis. The pathogenic capacity of SCVs compared to phenotypically normal strains is variable depending on the attribute examined, with some studies showing reduced virulence of SCVs and others demonstrating normal or heightened virulence. Recently, the nematode Caenorhabditis elegans has been successfully employed as an alternative host to investigate virulence mechanisms of a variety of bacterial pathogens, including S. aureus. In this study, we show that clinical SCVs as well as hemB- and menD-deficient mutants of S. aureus are greatly reduced in virulence in the C. elegans infection model.

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Figures

FIG. 1.

FIG. 1.

Survival of C. elegans on clinically isolated S. aureus SCVs. Survival of nematodes fed S. aureus A22223I (clinical wild-type isolate; closed triangles; n = 69) versus A22223II (hemin-auxotrophic SCV; open triangles; n = 65) and A22616/5 (clinical wild-type isolate; closed diamonds; n = 55) versus A22616/3 (menadione-auxotrophic SCV; open diamonds; n = 56) is shown. Survival was plotted using the Kaplan-Meier method, and pairwise comparisons using the log rank test between the SCV and matched wild-type isolates were significant at a P value of <0.0001.

FIG. 2.

FIG. 2.

Survival of C. elegans on SCV hemB mutants. (A) Survival of nematodes fed S. aureus Newman (wild type; closed squares; n = 57), III33 (hemB SCV; open squares with a solid line; n = 61), and KM2 (_hemB_-complemented III33; open squares with a dashed line; n = 52). (B) Survival of nematodes fed S. aureus COL (wild type; closed circles; n = 55), Ia48 (hemB SCV; open circles with a solid line; n = 56), and KM1 (_hemB_-complemented Ia48; open circles with a dashed line; n = 61). Survival was plotted using the Kaplan-Meier method. Pairwise comparisons using the log rank test by strain were as follows: Newman versus III33, III33 versus KM2, COL versus Ia48, and Ia48 versus KM1 (all P < 0.0001).

FIG. 3.

FIG. 3.

Survival of C. elegans on SCV menD mutants. (A) Survival of nematodes fed S. aureus 8325-4 (wild type; closed diamonds; n = 91), DB24 (menD SCV; open diamonds with a solid line; n = 83), and DB25 (_menD_-repaired DB24; open diamonds with a dashed line; n = 92). (B) Survival of nematodes fed S. aureus COL (wild type; closed circles; n = 92) and COL menD (menD SCV; open circles; n = 93). Survival was plotted using the Kaplan-Meier method. Pairwise comparisons using the log rank test by strain were as follows: 8325-4 versus DB24, DB24 versus DB24, and COL versus COL menD (all P < 0.0001).

FIG. 4.

FIG. 4.

Colonization of the C. elegans digestive tract. Differential interference contrast photomicrographs of the terminal bulb and anterior intestinal tract of nematodes after feeding for 20 h on lawns of (A) COL, (B) Ia48, or (C) KM1 are shown.

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References

    1. Bae, T., A. K. Banger, A. Wallace, E. M. Glass, F. Aslund, O. Schneewind, and D. M. Missiakas. 2004. Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing. Proc. Natl. Acad. Sci. USA 101:12312-12317. - PMC - PubMed
    1. Bates, D. M., C. von Eiff, P. J. McNamara, G. Peters, M. R. Yeaman, A. S. Bayer, and R. A. Proctor. 2003. Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney. J. Infect. Dis. 187:1654-1661. - PubMed
    1. Baumert, N., C. von Eiff, F. Schaaff, G. Peters, R. A. Proctor, and H. G. Sahl. 2002. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Microb. Drug Resist. 8:253-260. - PubMed
    1. Beenken, K. E., J. S. Blevins, and M. S. Smeltzer. 2003. Mutation of sarA in Staphylococcus aureus limits biofilm formation. Infect. Immun. 71:4206-4211. - PMC - PubMed
    1. Begun, J., C. D. Sifri, S. Goldman, S. B. Calderwood, and F. M. Ausubel. 2005. Staphylococcus aureus virulence factors identified by using a high-throughput Caenorhabditis elegans-killing model. Infect. Immun. 73:872-877. - PMC - PubMed

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