Mutation of Agr Is Associated with the Adaptation of Staphylococcus aureus to the Host during Chronic Osteomyelitis

SULIGOY CM; LATTAR SM; NOTO LLANA, M; GONZALEZ, CD; ALVAREZ, LP; ROBINSON, DA; GOMEZ, MI; BUZZOLA, FR; SORDELLI, DO

Frontiers in Cellular in Infection Microbiology

Frontiers Editorial

Año: 2018

2235-2988

Selection pressures exerted on Staphylococcus aureus by host factors may lead to theemergence of mutants better adapted to the evolving conditions at the infection site.This study was aimed at identifying the changes that occur in S. aureus exposed to thehost defense mechanisms during chronic osteomyelitis and evaluating whether thesechanges affect the virulence of the organism. Genome assessment of two S. aureusisolates collected 13 months apart (HU-85a and HU-85c) from a host with chronicosteomyelitis was made by whole genome sequencing. Agr functionality was assessedby qRT-PCR. Isolates were tested in a rat model of osteomyelitis and the bacterialload (CFU/tibia) and the morphometric osteomyelitic index (OI) were determined. Theability of the isolates to trigger the release of proinflammatory cytokines was determinedon macrophages in culture. Persistence of S. aureus within the host resulted in anagrC frameshift mutation that likely led to the observed phenotype. The capacity tocause bone tissue damage and trigger proinflammatory cytokines by macrophages ofthe agr-deficient, unencapsulated derivative (HU-85c) was decreased when comparedwith those of the isogenic CP8-capsulated parental strain (HU-85a). By comparison, nosignificant differences were found in the bacterial load or the OI from rats challengedwith isogenic Reynolds strains [CP5, CP8, and non-typeable (NT)], indicating that lack ofCP expression alone was not likely responsible for the reduced capacity to cause tissuedamage in HU-85c compared with HU-85a. The production of biofilm was significantlyincreased in the isogenic derivative HU-85c. Lack of agr-dependent factors makes S.aureus less virulent during chronic osteomyelitis and alteration of the agr functionalityseems to permit better adaptation of S. aureus to the chronically infected host.