Regulation of capsule gene expression by group A Streptococcus during pharyngeal colonization and invasive infection

Capsular polysaccharide production by group A Streptococcus (GAS) is contro lled by transcription of the has operon that encodes the enzymes uniquely r equired for synthesis of the hyaluronic acid polysaccharide. To investigate the regulation of capsule gene expression during infection, we developed a reporter strain of GAS in which the has operon promoter directed transcrip tion of green fluorescent protein (GFP). Gfp expression was triggered withi n minutes after introduction of the reporter strain into the peritoneal cav ity of mice, as evidenced by the recovery of highly fluorescent GAS from th e peritoneum 1 h after challenge. Capsule gene expression was also stimulat ed in the bloodstream of infected mice, as intensely fluorescent bacteria w ere observed in blood samples collected after either intraperitoneal or int ravenous challenge. Using a similar approach, we also observed rapid induct ion of capsule gene expression in bacteria inoculated into the pharynx of b aboons. Compared to the inoculum, increased green fluorescence was recorded in bacteria recovered from throat swabs collected 1 h after inoculation in all five animals studied. We conclude that introduction of GAS into the ph arynx or into deep tissues results in rapid induction of has operon express ion, a critical adaptive response that enhances GAS survival in the infecte d host.