Staphylococcal accessory regulator (sar) in conjunction with agr contributes to Staphylococcus aureus virulence in endophthalmitis

Abstract

Previous studies showed that an agr mutant strain of Staphylococcus aureus was partially attenuated in virulence compared to a parental strain in experimental endophthalmitis. The purpose of this study was to determine whether the sar locus, either alone or through interactions with agr, contributes to the regulation of virulence in S. aureus endophthalmitis. Experimental endophthalmitis was established by the midvitreous injection of approximately 30 CFU of S. aureus RN6390 or the isogenic attenuated strains RN6911 (agr mutant), ALC136 (sar mutant), and ALC135 (agr sar double mutant). Unexpectedly, the rate of reduction in electroretinographic B-wave amplitude in eyes infected with strain ALC136 (sar mutant) was not significantly different from the parental strain on postinfection day (PID) 5 (10% retention). In contrast, ALC135 (agr sar double mutant)infected eyes retained 73% of preoperative B-wave amplitude on PID 5. Therefore, unlike agr, a mutation in the sar locus alone does not alter the overall virulence of wild-type S. aureus in experimental endophthalmitis. However, the combined effect of insertional mutations in both the sar and agr global regulators leads to near-complete attenuation of virulence.

Staphylococcal superantigen-like genes, ssl5 and ssl8, are positively regulated by Sae and negatively by Agr in the Newman strain

“…An analogous phenomenon such as enhanced repression of exotoxin-encoding genes in double mutants of regulatory genes in S. aureus is not uncommon. For example, sar and agr double mutants are less virulent compared with the agr single mutant (Booth et al, 1997). Differences in the transcript levels of regulatory genes (agr, sarA, sigB, and saeR/S) have been reported between COL and Newman strains that correlate well with the expression of virulence-associated genes (Rogasch et al, 2006).…”

Staphylococcus aureus pathogenicity on Arabidopsis thaliana is mediated either by a direct effect of salicylic acid on the pathogen or by SA‐dependent, NPR1‐independent host responses

“…Further, sarA activates the agr regulatory system that is linked to several virulence factors (Blevins et al, 1999(Blevins et al, , 2002Chan and Foster, 1998). The sarA and agr loci have been implicated in the virulence of a number of disease models (Booth et al, 1997;Cheung and Ying, 1994;Kielian et al, 2001). sarA is essential for biofilm formation in S. aureus (Beenken et al, 2003).…”

Regulation of virulence determinants inStaphylococcus aureus: complexity and applications

“…Ocular infection models have been developed in rabbits. Experimental endophthalmitis studies showed that an agr mutant causes less severe clinical and histological signs than the wild-type strain [90], strongly suggesting that toxin production contributes to virulence. This was further confirmed in the same model of endophthalmitis, where agr, but not sarA alone, influenced virulence.…”

“…This was further confirmed in the same model of endophthalmitis, where agr, but not sarA alone, influenced virulence. However, the double mutant had a greater effect [91]. In a rat endophthalmitis model, Giese et al [92] reported that an agr/sarA double mutant strain induced less inflammatory cell recruitment than the wild-type strain, implying that pore-forming toxins may play a major role.…”