CONICET | Buscador de Institutos y Recursos Humanos

Staphylococcus aureus is a highly prevalent opportunistic,multifactorial pathogen that can infect, replicate and persist in humans anddomestic animals of economic importance. The S. aureus genome carries a vast array of genescoding for virulence and evasion factors. The capacity of S. aureus to cause a wide variety of diseasespartially depends on its ability to express a number of these factors that,acting in concert, permit adaptation of the pathogen to distinct and changingenvironmental niches during infection. The evolution of S. aureus within affected tissue appears to play akey role in persistence of the microorganism and chronicity of the infection.Selection pressure exerted on S. aureusby hostfactors may determine the emergence of mutants better adapted to the evolvingconditions at the infection site. There is undisputable evidence showing thatcertain diseases caused by S. aureus, such as osteomyelitis, startas acute and later develop into a chronic illness. This study identifiedchanges that occur in S. aureusexposed tothe host defense mechanisms during infection and evaluated whether thesechanges affect the virulence of the organism. To this purpose, we studied S. aureus isolates from single patient with chronicosteomyelitis and from the same infection site. In one case, strains SaT0 andSaT13 which were isolated 13-months apart, belonged in the same clonal complexgroup (CC1) and shared the same sequence type (ST188), PFGE type, spa type (t189) and Agr type (type I). Strain SaT0 expressed capsularpolysaccharide type 8 (CP8) (at the beginning of the infectious process)whereas strain SaT13 did not (13 months later). Furthermore, the strain SaT0expressed alpha and beta-haemolysins whereas strain SaT13 did not. It wasdemonstrated by real time PCR that these phenotypic differences were due to thelack of expression in strain SaT13 of the effector molecule of the globalregulator agr (RNAIII). S. aureus strains were tested in a rat model ofosteomyelitis and the bacterial load (CFU/tibia) and the morphometricosteomyelitic index (OI) were determined. The bacterial load and the OI of the agr deficient strain, which were unable to produce CP, were significantlylower than those of the parental wild-type. No significant differences werefound in the bacterial load or the OI from rats challenged with the isogenicReynolds strains (CP5, CP8 and NT non-typeable) indicating that lack of capsuleexpression alone was not the sole responsible for reduced virulence of themutants. Small colony variants (SCVs) emerged in the tibias of ratsexperimentally infected with all S.aureus strainstested and the number of SCV CFUs increased with the length of the infectionprocess. Whereas there is no doubt thatlack of agr-dependent factors turns S. aureus less virulent, mutations that alter the agr functionality seem to permit a better adaptation of S. aureus to the host for persistence and infectionchronicity.

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