agr function in clinical Staphylococcus aureus isolates

Abstract

The accessory gene regulator (agr) of Staphylococcus aureus is a global regulator of the staphylococcal virulon, which includes secreted virulence factors and surface proteins. The agr locus is important for virulence in a variety of animal models of infection, and has been assumed by inference to have a major role in human infection. Although most human clinical S. aureus isolates are agr+, there have been several reports of agr-defective mutants isolated from infected patients. Since it is well known that the agr locus is genetically labile in vitro, we have addressed the question of whether the reported agr-defective mutants were involved in the infection or could have arisen during post-isolation handling. We obtained a series of new staphylococcal isolates from local clinical infections and handled these with special care to avoid post-isolation mutations. Among these isolates, we found a number of strains with non-haemolytic phenotypes owing to mutations in the agr locus, and others with mutations elsewhere. We have also obtained isolates in which the population was continuously heterogeneous with respect to agr functionality, with agr+ and agr− variants having otherwise indistinguishable chromosomal backgrounds. This finding suggested that the agr− variants arose by mutation during the course of the infection. Our results indicate that while most clinical isolates are haemolytic and agr+, non-haemolytic and agr− strains are found in S. aureus infections, and that agr+ and agr− variants may have a cooperative interaction in certain types of infections.

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

“…We investigated whether surface-attached pro- and anti-quorum-sensing molecules could control S. aureus behaviors in the more natural and clinically-relevant context of S. aureus strains that are capable of producing AIP-I 37 , unlike the reporter strain used above. For this analysis, we introduced the fluorescent quorum-sensing reporter genes into wild-type S. aureus agr-I (RN6390b) and S. aureus MRSA agr-I .…”

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

“…This population heterogeneity is likely to be advantageous for S. aureus since agr ϩ strains are more potent in initiating infections (48), while the ⌬agr strains are more potent in the establishment of chronic infections through biofilm formation (49). Our finding that nonspreading cells can "hitch-hike" along with the spreaders on soft agar plates would suggest that a similar phenomenon might "help" ⌬agr cells also in the colonization of wet surfaces, either in the human host or in other habitats.…”

How Staphylococcus aureus biofilms develop their characteristic structure

“…In that regard, it is important to stress that many previous studies on S. aureus biofilms were performed in laboratory strains, several of which were Agr-dysfunctional (such as strain SA113) and likely selected because of their extended biofilm thickness. Of note, agr mutants are also frequently isolated clinically from biofilm-covered devices, presumably because compact and extended biofilms are of a certain advantage to the bacteria in specific stages of chronic infection (25); notably, however, these strains likely represent a dead end of infection, because they lack the capacity to disseminate within the body (4) or establish infection in other hosts (26).…”