The Impacts of msaABCR on sarA -Associated Phenotypes Are Different in Divergent Clinical Isolates of Staphylococcus aureus

• Published in: Infection and immunity 2020-01, Vol.88 (2)
• Main Authors: Rom, Joseph S, Ramirez, Aura M, Beenken, Karen E, Sahukhal, Gyan S, Elasri, Mohamed O, Smeltzer, Mark S
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Infections; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilms - growth & development; Disease Models, Animal; Gene Expression Regulation, Bacterial; Genotype; Mice, Inbred C57BL; Mutation; Osteomyelitis - microbiology; Osteomyelitis - pathology; Phenotype; Staphylococcal Infections - microbiology; Staphylococcus aureus - classification; Staphylococcus aureus - isolation & purification; Staphylococcus aureus - physiology; Virulence Factors - genetics; Virulence Factors - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00530-19

The staphylococcal accessory regulator ( ) plays an important role in infections, including osteomyelitis, and the operon has been implicated as an important factor in modulating expression of Thus, we investigated the contribution of to -associated phenotypes in the clinical isolates LAC and UAMS-1. Mutation of resulted in reduced production of SarA and a reduced capacity to form a biofilm in both strains. Biofilm formation was enhanced in a LAC mutant by restoring the production of SarA, but this was not true in a UAMS-1 mutant. Similarly, extracellular protease production was increased in a LAC mutant but not a UAMS-1 mutant. This difference was reflected in the accumulation and distribution of secreted virulence factors and in the impact of extracellular proteases on biofilm formation in a LAC mutant. Most importantly, it was reflected in the relative impact of mutating as assessed in a murine osteomyelitis model, which had a significant impact in LAC but not in UAMS-1. In contrast, mutation of had a greater impact on all of these and phenotypes than mutation of , and it did so in both LAC and UAMS-1. These results suggest that, at least in osteomyelitis, it would be therapeutically preferable to target rather than to achieve the desired clinical result, particularly in the context of divergent clinical isolates of .