Interactions between β-haemolytic streptococci and the human host. Heart, skin and beyond

Sammanfattning: Group C and G streptococci (GCS/GGS) and group A streptococci (GAS) belong to β-haemolytic streptococci (BHS). GCS/GGS can further be species determined to S. dysgalactiae, whereas S. pyogenes are GAS. S. dysgalactiae and S. pyogenes cause similar diseases, (e.g., skin and soft tissue infections, erysipelas, bacteraemia, and infective endocarditis (IE)). Erysipelas often presents as a sharply demarcated oedematous erythema and often reoccurs in the same host. The diagnosis relies on the clinical presentation since cultures from blood and/or wounds often are negative. IE due to BHS is rare but is a challenging infection to treat. Combination therapy using a β-lactam and an aminoglycoside has been employed to treat the condition, but the evidence for synergy between the two antibiotics is weak. This thesis began investigating erysipelas and predominantly found GCS/GGS, but also GAS as important pathogens to erysipelas, (Paper I). To further investigate the disease panorama of GCS/GGS, the second study comprised cases of IE due to S. dysgalactiae from a nationwide registry. IE with S. dysgalactiae was found to have an acute onset of symptoms with substantial mortality and embolic event rate, (Paper II). Synergy between penicillin G and gentamicin was observed in some blood isolates of S. dysgalactiae. However, in most cases, penicillin G alone showed bactericidal action so strong, that any further killing action of gentamicin was difficult to detect. Recurrent infections with S. dysgalactiae, involving erysipelas but also bacteraemia, are common. The cell surface attached M protein is an important virulence determinant for the bacteria. There are different M proteins which render an antigenic diversity and facilitate the bacteria’s evasion of the host defence system. In a prospectively based study, type-specific antibodies were developed in convalescent serum from patients with prior bacteraemia with S. dysgalactiae, (Paper III). However, further analysis with bactericidal and phagocytosis assays could not establish that these evolved antibodies opsonised the bacteria or enhanced the killing of the bacteria. The quest for prognostic factors in bacteraemia with BHS is challenging. Time to positivity (TTP) from blood cultures may reflect bacterial concentration in blood and was identified as an independent prognostic factor for 30-day mortality in invasive infections due to both S. pyogenes and S. dysgalactiae respectively, (Paper IV and V). All things considered, this thesis highlights the clinical and microbiological aspects of infections caused by BHS and their interactions with the human host. Recurrent infections due to the bacteria are common, and a lack of development of opsonising antibodies may partially explain the presence of recurrent bacteraemia with S. dysgalactiae.