Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing

doi:10.1073/pnas.0404728101

Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing

^*Committee on Microbiology and Departments of ^†Molecular Genetics and Cell Biology and ^‡Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637; ^§Mathematics and Computer Sciences Division, Argonne National Laboratory, Argonne, IL 60439; and ^¶Center for Genomics and Bioinformatics, Karolinska Institutet, 17177 Stockholm, Sweden

Communicated by Robert Haselkorn, University of Chicago, Chicago, IL, July 1, 2004 (received for review June 10, 2004)

Abstract

Staphylococcus aureus is the leading cause of wound and hospital-acquired infections worldwide. The emergence of S. aureus strains with resistance to multiple antibiotics requires the identification of bacterial virulence genes and the development of novel therapeutic strategies. Herein, bursa aurealis, a mariner-based transposon, was used for random mutagenesis and for the isolation of 10,325 S. aureus variants with defined insertion sites. By screening for loss-of-function mutants in a Caenorhabditis elegans killing assay, 71 S. aureus virulence genes were identified. Some of these genes are also required for S. aureus abscess formation in a murine infection model.

Footnotes

↵ ** To whom correspondence should be addressed at: Department of Biochemistry and Molecular Biology, University of Chicago, 920 East 58th Street, Chicago, IL 60637. E-mail: strains{at}bsd.uchicago.edu.
↵ ∥ Present address: European Patent Office, 2288 Rijswijk, The Netherlands.
Abbreviations: TSA, tryptic soy agar; Tn917, transposon 917.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database [accession nos. AY672108 (pFA545) and AY672109 (pBursa)].