Diminished virulence of a sar-/agr- mutant of Staphylococcus aureus in the rabbit model of endocarditis.

Abstract

Microbial pathogenicity in Staphylococcus aureus is a complex process involving a number of virulence genes that are regulated by global regulatory systems including sar and agr. To evaluate the roles of these two loci in virulence, we constructed sar-lagr-mutants of strains RN6390 and RN450 and compared their phenotypic profiles to the corresponding single sar-and agr-mutants and parents. The secretion of all hemolysins was absent in the sar-lagr-mutants while residual 8-hemolysin activity remained in single agr-mutants. The fibronectin binding capacity was significantly diminished in both single sar-mutants and double mutants when compared with parents while the reduction in fibrinogen binding capacity in the double mutants was modest. In the rabbit endocarditis model, there was a significant decrease in both infectivity rates and intravegetation bacterial densities with the double mutant as compared to the parent (RN6390) at 10'-10' CFU inocula despite comparable levels of early bacteremia among various challenge groups. Notably, fewer bacteria in the double mutant group adhered to valvular vegetations at 30 min after challenge (106 CFU) than the parent group. These studies suggest that both the sar and agr loci are involved in initial valvular adherence, intravegetation persistence and multiplication of S. aureus in endocarditis. (J.

Response of corneal epithelial cells toStaphylococcus aureus

“…S. aureus RN6390, 67 isogenic mutant of RN6390, ALC135 (agr::tetM, sar::Tn917/LTV1) 69 (generously provided by Ambrose Cheung, Dartmouth Medical School, Hanover, NH), and Lactococcus lactis strain MG1363 (generously provided by Todd R. Klaenhammer, North Carolina State University, Raleigh, NC) were used in this study, and routinely cultured in brain heart infusion (BHI) broth (BD San Jose, CA) broth at 37°C. For challenge experiments, overnight cultures were diluted 1:50 into 25 ml of pre-warmed BHI broth and grown at S. aureus clinical isolate expressing toxic shock syndrome toxin-1 (TSST-1).…”

Quorum sensing in bacterial virulence

“…Many studies have found that agr is required for virulence in models of septic arthritis, osteomyelitis, endophthalmitis and pulmonary infections (Abdelnour et al, 1993;Booth et al, 1997;Gillaspy et al, 1995;Heyer et al, 2002). However, other evidence seems to question the role of the agr system in virulence in other models (Cheung et al, 1994;Kielian et al, 2001). In cystic fibrosis (CF) patients with S. aureus infections, the agr system was inactive, suggesting that agr activation may not be necessary for infection (Goerke et al, 2000).…”

Alternative transcription factor sigmaSB of Staphylococcus aureus: characterization and role in transcription of the global regulatory locus sar

“…1). Interestingly, the pathogenicity of S. aureus strains lacking either agr or sar is reduced significantly, and those strains that lack both the agr and the sar loci are almost completely attenuated (1,10,39).In this paper, we report the purification of the S. aureus SigB protein, designated SB , and promoter-specific transcription by the core RNAP reconstituted with SB . Transcriptional analysis of the sar operon by the core RNAP reconstituted with SB provides the first clue as to how the biosynthesis of some of the toxins can be modulated in response to various physiological and environmental stress conditions.…”

“…1). Interestingly, the pathogenicity of S. aureus strains lacking either agr or sar is reduced significantly, and those strains that lack both the agr and the sar loci are almost completely attenuated (1,10,39).…”