Critical role of the group A streptococcal capsule in pharyngeal colonization and infection in mice.

Abstract

To study the role of the group A streptococcal capsule in pharyngeal colonization, we used two acapsular mutants derived from a type 24 strain of group A Streptococcus by transposon mutagenesis. One mutant had a stable acapsular phenotype due to a transposon-associated chromosomal deletion of essential capsule synthetic genes, while the second mutant could revert to the encapsulated phenotype at a low frequency (<10-4) upon spontaneous excision of the transposon from the capsule-synthesis region of the chromosome. Both acapsular mutants were sensitive to phagocytic killing in vitro and had reduced virulence in mice after intraperitoneal challenge. Mice inoculated intranasally with the stable acapsular mutant rapidly cleared the organisms from the pharynx, and no mice died. In contrast, throat cultures of animals challenged with the revertible mutant yielded many encapsulated revertants, and mortality was similar to that of animals challenged with the parent strain. The rapid emergence of a population of encapsulated revertants in the pharynx implies that the capsule conferred a powerful selective advantage in this environmental niche. Together with the complete avirulence of the stable acapsular mutant, these observations indicate that the hyaluronic acid capsule plays a critical role in colonization and infection of the pharynx by group A streptococci.A critical first step in the pathogenesis of streptococcal pharyngitis is colonization of the mucosal epithelium of the pharynx by group A streptococci (GAS). Successful colonization leads to bacterial proliferation in the pharynx, local tissue invasion, and host inflammatory responses that result in the clinical manifestations of pharyngitis. Pharyngeal infection occasionally progresses to invasion of deeper tissues to produce local suppurative complications or systemic infection. In addition, colonization of the pharynx is not only important as a prelude to pharyngitis and related infectious syndromes but also appears to be an absolute prerequisite for development of the postinfectious autoimmune syndrome of acute rheumatic fever.Studies of adherence of GAS to epithelial cells have implicated several bacterial surface molecules in the attachment process including lipoteichoic acid, M protein, and fibronectin-binding proteins (reviewed in ref.

CD44 as a receptor for colonization of the pharynx by group A Streptococcus

“…Several GAS surface molecules in addition to the hyaluronic acid capsule have been implicated in adherence of the organisms to epithelial cells; however, these alternative adhesins failed to mediate effective colonization when the interaction between the hyaluronic acid capsule and epithelial CD44 was perturbed by a blocking antibody, by exogenous hyaluronic acid, or by reduced epithelial expression of CD44. Strains of GAS that lack a hyaluronic acid capsule adhere to epithelial cells in vitro at least as well as encapsulated strains; however, capsule-deficient strains colonize the pharynx poorly in vivo and are avirulent in experimental infection models (16,17,29). Therefore, effective colonization of the pharynx by virulent strains of GAS appears to require the specific interaction of the GAS capsular polysaccharide with CD44.…”

“…In contrast, the GAS capsular polysaccharide is invariant in structure and is highly conserved among GAS isolates (14,15). Experimental infection studies in mice have shown that mutant strains of GAS deficient in capsular polysaccharide fail to cause infection after intranasal inoculation (16,17). Because the capsular polysaccharide forms an outermost layer on the bacterial surface, it is likely to be important in adhesive interactions between the bacterial cell and the pharyngeal epithelium.…”

Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection

“…In mice, GAS strains that lack the hyaluronic acid capsule are more efficiently cleared from the throat (Wessels and Bronze, 1994;Husmann et al, 1997). M protein expression was also required for pharyngeal colonization in a rat model, but this effect was not reproduced in mice (Hollingshead et al, 1993;Husmann et al, 1997).…”

Characterization of a Two-component System in Streptococcus pyogenes Which Is Involved in Regulation of Hyaluronic Acid Production

“…Increased isolation of mucoid strains of GAS from human outbreaks of rheumatic fever as well as severe invasive infections suggests that capsule production may be an important virulence factor in these diseases (5). In addition, production of hyaluronic acid by GAS is apparently important in the initial stages of colonization of the upper respiratory tract of intranasally inoculated mice (6,7). This evidence is supported by the observation that hyaluronic acid can function as an adhesin capable of binding to CD44 on keratinocytes found on the pharyngeal mucosa and skin (8).…”