Nonpolar inactivation of the hypervariable streptococcal inhibitor of complement gene (sic) in serotype M1 Streptococcus pyogenes significantly decreases mouse mucosal colonization

Group A Streptococcas (GAS) is a human pathogen that commonly infects the u pper respiratory tract. GAS serotype M1 strains are frequently isolated fro m human infections and contain the gene encoding the hypervariable streptoc occal inhibitor of complement protein (Sic), It was recently shown that Sic variants were rapidly selected on mucosal surfaces in epidemic waves cause d by M1 strains, an observation suggesting that Sic participates in host-pa thogen interactions on the mucosal surface (N. P. Hoe, K. Nakashima, S, Luk omski, D. Grigsby, M. Liu, P, Kordari, S.-J. Dou, X. Pan, J. Vuopio-Varkila , S. Salmelinna, A. McGeer, D. E. Low, B. Schwartz, A. Schuchat, S, Naidich , D, De Lorenzo, Y.-X. Fu, and J, M, Musser, Nat, Med. 5:924-929, 1999), To test this idea, a new nonpolar mutagenesis method employing a spectinomyci n resistance cassette was used to inactivate the sk gene in an MI GAS strai n, The isogenic Sie-negative mutant strain was significantly (P < 0.019) im paired in ability to colonize the mouse mucosal surface after intranasal in fection. These results support the hypothesis that the predominance of M1 s trains in human infections is related, in part, to a Sie-mediated enhanced colonization ability.