Adaptation of Staphylococcus aureus to the host during chronic infection is associated with decreased virulence

SULIGOY CM; DOTTO CM; LOMBARTE SERRAT A; RIVIERE AN; SORDELLI DO; ALVAREZ LP, BARBAGELATA MS, CHEUNG AL, SORDELLI DO AND BUZZOLA FR

Congreso; XI Congreso Argentino de Microbiología General; 2015

Staphylococcus aureus is a highly prevalent opportunistic, multifactorial pathogen that can infect, replicate and persist in humans and domestic animals of economic importance. The S. aureus genome carries a vast array of genes coding for virulence and evasion factors. The capacity of S. aureus to cause a wide variety of diseases partially depends on its ability to express a number of these factors that, acting in concert, permit adaptation of the pathogen to distinct and changing environmental niches during infection. The evolution of S. aureus within affected tissue appears to play a key role in persistence of the microorganism and chronicity of the infection. Selection pressure exerted on S. aureus by host factors may determine the emergence of mutants better adapted to the evolving conditions at the infection site. There is undisputable evidence showing that certain diseases caused by S. aureus, such as osteomyelitis, start as acute and later develop into a chronic illness. This study identified changes that occur in S. aureus exposed to the host defense mechanisms during infection and evaluated whether these changes affect the virulence of the organism. To this purpose, we studied S. aureus isolates from single patient with chronic osteomielitis and from the same infection site. In one case, strains SaT0 and SaT13 which were isolated 13-months apart, belonged in the same clonal complex group (CC1) and shared the same sequence type (ST188), PFGE type, spa type (t189) and Agr type (type I). Strain SaT0 expressed capsular polysaccharide type 8 (CP8) (at the beginning of the infectious process) whereas strain SaT13 did not (13 months later). Furthermore, the strain SaT0 expressed alpha and beta- haemolysins whereas strain SaT13 did not. It was demonstrated by real time PCR that these phenotypic differences were due to the lack of expression in strain SaT13 of the effector molecule of the global regulator agr (RNAIII). S. aureus strains were tested in a rat model of osteomyelitis and the bacterial load (CFU/tibia) and the morphometric osteomyelitic index (OI) were determined. The bacterial load and the OI of the agr deficient strain, which were unable to produce CP, were significantly lower than those of the parental wild-type. No significant differences were found in the bacterial load or the OI from rats challenged with the isogenic Reynolds strains (CP5, CP8 and NT non-typeable) indicating that lack of capsule expression alone was not the sole responsible for reduced virulence of the mutants. Small colony variants (SCVs) emerged in the tibias of rats experimentally infected with all S. aureus strains tested and the number of SCV CFUs increased with the length of the infection process. Whereas there is no doubt that lack 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 infection chronicity.