Einfluss von genetischer Plastizität auf die Art und Schwere einer bakteriellen Infektionserkrankung: Einsatz von beta-hämolytischen Streptokokken der Gruppe A als Modellorganismus

Beta-hemolytic group A streptococci (GAS) are a major cause of human morbidity and mortality due to infectious diseases worldwide. Although most infections due to GAS are limited to the skin and nasopharyngeal mucosa, some involve severe invasive disease, causing streptococcal toxic shock–like syndrome and necrotizing fasciitis. Many hypotheses, either focusing on impaired host defense or enhanced virulence of GAS itself, trying to explain the diversity of streptococcal diseases, have emerged. There has been a marked attenuation in the incidence of severe invasive GAS infections in the beginning of the twentieth century, followed by a resurgence and persistence of serious GAS infections since the mid-1980s. To investigate the effect of toxin-gene profile heterogeneity among endemic invasive European group A streptococcal isolates on the severity and location of the respective infection, we determined the toxin-gene profiles of 239 endemic, invasive group A streptococcal (GAS) isolates that circulated, within a 5-year period, in European university hospitals. Profiling was performed by use of multiplex polymerase chain reaction that screened for 9 streptococcal pyrogenic exotoxins (speA, speB, speC, speF, speG, speH, speJ, ssa, and smeZ). Analysis revealed that invasive GAS isolates do not share a common toxin-gene profile. Although all emm types were characterized by several different toxin-gene profiles, a predominance of 1 or 2 toxin-gene profiles could be observed, reflecting that a few invasive clones have spread successfully throughout the world. Remarkably, statistical pair-wise analysis of individual toxin genes revealed that strains that did not share the predominant profile still showed a nonrandom distribution of key toxin genes characteristic of the specific emm type. In this context, it is striking that different emm sequence types, although presenting very distinct toxin-gene profiles, share a number of characteristics, which argues for a selective and/or biological advantage. Only a few emm types are characterized by the coexistence of speA and speC. Among 50 different emm types, only 2 (28 and 22.2) possessed a considerable number of isolates carrying speA and speC simultaneously. Apart from these emm types, only emm12 (2/24), emm1 (1/71), emm3.1 (1/34), and emmST6735 (1/1) demonstrated coexistence of speA and speC. A similar finding was made for ssa and smeZ; both coexisted rarely in our collection of GAS strains. Our findings suggest that invasive GAS isolates do not share a common toxin-gene profile, indicating that a specific set of spe genes is not required for enhanced virulence. However, almost every emm type was characterized by the predominance of 1 or 2 toxin-gene profiles, clearly supporting the concept of clonal distribution. However, most toxin-gene profiles, including the less frequent ones, were rather exclusive for a single emm type, possibly defining emm sequence types as barriers to horizontal gene flow. This was further supported by statistical pairwise analysis of individual toxin genes, which revealed that those strains not sharing the predominant profile still showed a nonrandom distribution of key toxin genes characteristic of the specific emm type. This could indicate that M proteins function directly or indirectly as barriers for horizontal gene exchange.