Tissue tropisms in group A streptococcal infections

Abstract

Group A Streptococcus (GAS) is a human-specific pathogen that is highly prevalent throughout the world. The vast majority of GAS infections lead to a mild disease involving the epithelial surfaces of either the throat or skin. The concept of distinct sets of 'throat' and 'skin' strains of GAS has long been conceived. From an ecological standpoint, the epithelium of the throat and skin are important because it is where the organism is most successful in reproducing and transmitting to new hosts. This article examines key features of the epidemiology, population biology and molecular pathogenesis that underlie the tissue site preferences for infection exhibited by GAS, with an emphasis on work from our laboratory on skin tropisms. Recombinational replacement with orthologous gene forms, following interspecies transfer, appears to be an important genetic step leading up to the exploitation of new niches by GAS.

Figure 1. Population-based surveys of group A Streptococcus infection

Group A streptococci isolated from patients with either superficial throat or skin infections, in several locales throughout the world by numerous investigators, had been characterized for emm type [–25]; based on the emm type, the emm pattern group is inferred [12]. The percentage of isolates in each emm pattern group is depicted for the eight pharyngitis and six impetigo collections of group A streptococci. ^†Aboriginal populations of tropical Australia.

Figure 2. Map of the emm and FCT regions of the group A Streptococcus genome

The most common combinations of genes present within the emm and FCT regions of over 100 group A Streptococcus strains are depicted in accordance to emm pattern grouping, based on findings reported in [–34,42]. Shown are emm pattern A–C (blue), D (red) and E (purple). For pattern D and E strains, the upstream emm-like genes is also known as mrp and the downstream emm-like gene is also known as enn.

Figure 3. Growth dynamics of group A Streptococcus during skin infection in the humanized mouse

Pathological alterations throughout the time course of GAS infection of skin grafts in the humanized mouse are described. The time scale (top) designates the day postinoculation of skin with GAS. The growth stage of infecting GAS, determined based on the number of colony-forming units recovered from the skin at different time points, is also described. Panels on the right represent hematoxylin- and eosin-stained tissue sections obtained from GAS-infected skin biopsies. Black arrow: GAS aggregates; green arrowhead: dermal capillary containing PMNs. GAS: Group A Streptococcus; PMN: Polymorphonuclear leukocyte. Tissue sections reproduced with permission © American Society of Microbiology.