Comparative analysis of the roles of HtrA-like surface proteases in two virulent Staphylococcus aureus strains.
The HtrA surface protease is involved in the virulence of many pathogens, mainly by its role in stress resistance and bacterial survival. Staphylococcus aureus encodes two putative HtrA-like proteases, referred to as HtrA(1) and HtrA(2). To investigate the roles of HtrA proteins in S. aureus, we constructed htrA(1), htrA(2), and htrA(1) htrA(2) insertion mutants in two genetically different virulent strains, RN6390 and COL. In the RN6390 context, htrA(1) inactivation resulted in sensitivity to puromycin-induced stress. The RN6390 htrA(1) htrA(2) mutant was affected in the expression of several secreted virulence factors comprising the agr regulon. This observation was correlated with the disappearance of the agr RNA III transcript in the RN6390 htrA(1) htrA(2) mutant. The virulence of this mutant was diminished in a rat model of endocarditis. In the COL context, both HtrA(1) and HtrA(2) were essential for thermal stress survival. However, only HtrA(1) had a slight effect on exoprotein expression. The htrA mutations did not diminish the virulence of the COL strain in the rat model of endocarditis. Our results indicate that HtrA proteins have different roles in S. aureus according to the strain, probably depending on specific differences in the regulation of virulence factor and stress protein expression. We propose that HtrA(1) and HtrA(2) contribute to pathogenicity by controlling the production of certain extracellular factors that are crucial for bacterial dissemination, as revealed in the RN6390 background. We speculate that HtrA proteins act in the agr-dependent regulation pathway by assuring folding and/or maturation of some surface components of the agr system.
Rigoulay
Candice
C
Unité de Recherches Laitières et Génétique Appliquée, INRA, 78352 Jouy-en-Josas Cedex, France. rigoulay@jouy.inra.fr
Entenza
José M
JM
Halpern
David
D
Widmer
Eleonora
E
Moreillon
Philippe
P
Poquet
Isabelle
I
Gruss
Alexandra
A
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D004697:Endocarditis, Bacterial / Q000209:etiology; D004720:Endonucleases / Q000378:metabolism; D005809:Genes, Regulator / Q000502:physiology; D006461:Hemolysis; D000074923:High-Temperature Requirement A Serine Peptidase 2; D008836:Micrococcal Nuclease / Q000378:metabolism; D024101:Mitochondrial Proteins; D051381:Rats; D012697:Serine Endopeptidases / Q000502:physiology*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D037521:Virulence Factors / Q000032:analysis
D001426:Bacterial Proteins; D024101:Mitochondrial Proteins; D037521:Virulence Factors; C074002:nuc protein, staphylococcus; D004720:Endonucleases; D008836:Micrococcal Nuclease; D012697:Serine Endopeptidases; D000074923:High-Temperature Requirement A Serine Peptidase 2