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- Title
Identification of Staphyiococcus aureus virulence genes in a murine model of bacteraemia using signature-tagged mutagenesis.
- Authors
Ji-Min Mei; Nourbakhsh, Fahimeh; Ford, Charles W.; Holden, David W.
- Abstract
Signature-tagged mutagenesis with transposon Tn<em>917</em> was used to identify genes of <em>Staphylococcus aureus</em> required for virulence in a murine model of bacteraemia. Screening 1248 mutant strains in pools of 96 resulted in the provisional identification of 50 mutants attenuated in virulence. Subsequent individual analysis of many of these mutants confirmed that they are attenuated in virulence. DNA sequence analysis of regions flanking their transposon insertion points revealed that approximately half of them represent genes with unknown function, while most of the remainder are involved in nutrient biosynthesis and cell surface metabolism. Three mutants were found with transposon insertions in different positions in <em>femA</em>, and one mutant had an insertion in <em>femB</em>. Both <em>femA</em> and <em>femB</em> are involved in the formation of cell wall peptidogiycan pentaglycine cross-bridges. A further mutation occurred in a previously unknown gene that shares significant similarity to <em>femB</em>. Mutations were also obtained in <em>recA</em> and <em>lsp</em>(encoding the <em>S. aureus</em> prolipoprotein signal peptidase). On the basis of sequence similarities to proteins of known function, the products of other genes are probably involved in the synthesis of diaminopimelic acid (a component of peptidogiycan), maintenance of surface adhesins and cell surface membrane transport, showing that many components of the <em>S. aureus</em> cell surface are critical for the survival and replication of this pathogen in blood.
- Subjects
MUTAGENESIS; TRANSPOSONS; STAPHYLOCOCCUS aureus; MICROBIAL virulence; NUCLEOTIDE sequence; CELL membranes; GENETIC mutation
- Publication
Molecular Microbiology, 1997, Vol 26, Issue 2, p399
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1046/j.1365-2958.1997.5911966.x