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

Group A streptococcal (GAS) pharyngitis and the subsequent bacterial coloni zation of the human throat elicit an immune response that may precipitate a cute rheumatic fever in a susceptible host. To study the bacterial determin ants that influence throat colonization and induction of humoral immunity, we characterized the behavior of GAS strains in a baboon model. An M-type 3 clinical isolate of GAS typical of strains that cause pharyngitis and inva sive infection was recovered from the pharynx of six out of six baboons for at least 6 weeks after oral inoculation. By contrast, an isogenic mutant d eficient in M protein failed to colonize most animals or was rapidly cleare d. An isogenic mutant deficient in hyaluronic acid capsule colonized five o ut of six animals, but only persisted in the pharynx for 14-21 days. Coloni zed animals developed serum antistreptolysin O (SLO) and anti-nn protein im munoglobulin (Ig)G. The kinetics of the antibody responses were similar to those seen after human infection. Peak titres increased with the duration o f throat carriage. Colonization with GAS prevented recurrent colonization a fter challenge with the homologous wild-type strain, but not after challeng e with a strain of different M protein type. Early clearance of the M prote in-deficient strain was associated with increased susceptibility of this st rain to phagocytic killing in mon-immune serum, whereas clearance of the ac apsular strain was associated with increased susceptibility to phagocytic k illing in the presence of specific antibody. These studies support critical and distinct effects of the GAS M protein and capsule on throat colonizati on and induction of humoral immunity in a model that reproduces important f eatures of pharyngeal colonization and immune response following human infe ction.