Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made by serotype M1 group A Streptococcus strains that contributes to bacterial persistence in the mammalian upper respiratory tract. New variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic was analyzed. Of 636 persons living in diverse localities, 43% had anti-Sic serum antibodies, but only 16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in nasal wash specimens in high frequency. Linear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hypervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. These results support the hypothesis that selection of Sic variants occurs on mucosal surfaces by a mechanism that involves acquired host antibody.

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Streptococcal protective antigen (Spa) is a newly described surface protein of group A streptococci that was recently shown to evoke protective antibodies (J. B. Dale, E. Y. Chiang, S. Liu, H. S. Courtney, and D. L. Hasty, J. Clin. Investig. 103:1261-1268, 1999). In this study, we have determined the complete sequence of the spa gene from type 18 streptococci. Purified, recombinant Spa protein evoked antibodies that were bactericidal against type 18 streptococci, confirming the presence of protective epitopes. Sera from patients with acute rheumatic fever contained antibodies against recombinant Spa, indicating that the Spa protein is expressed in vivo and is immunogenic in humans. To determine the role of Spa in the virulence of group A streptococci, we created a series of insertional mutants that were (i) Spa negative and M18 positive, (ii) Spa positive and M18 negative, and (iii) Spa negative and M18 negative. The mutants and the parent M18 strain (18-282) were used in assays to determine resistance to phagocytosis, growth in human blood, and mouse virulence. The results show that Spa is a virulence determinant of group A streptococci and that expression of both Spa and M18 is required for optimal virulence of type 18 streptococci.Group A streptococci (GAS) are major human pathogens that cause a wide variety of illnesses, ranging from uncomplicated pharyngitis and pyoderma to life-threatening infections such as necrotizing fasciitis and toxic shock syndrome (23). The virulence of GAS is determined in part by their ability to resist opsonization by complement and phagocytic killing by neutrophils (14). It has been known for many years that these virulence characteristics are mediated in large part by the M protein on the surface of the organisms (16). In addition, the M proteins contain protective epitopes that elicit opsonic antibodies that promote phagocytic killing in the immune host (16). Previous studies have shown that insertional inactivation of the emm gene in some GAS serotypes results in an avirulent phenotype (7,19).In a recent study of type 18 streptococci, we found that inactivation of the emm 18 gene had only a minor effect on the ability of the mutant to grow in human blood and on the 50% lethal dose (LD 50 ) in mice compared to the M-positive parent strain (10). We used the M-negative mutant to identify a new surface protein, streptococcal protective antigen (Spa), that was distinct from M protein and contained protective epitopes which elicited bactericidal antibodies (10). The present study was undertaken to determine whether Spa functions as a virulence determinant of type 18 streptococci. Using a series of M-negative and Spa-negative mutants, we show that both of these surface proteins contribute to the virulence of type 18 streptococci. In addition, we have cloned and sequenced the complete spa gene, which allowed a direct comparison of its structure to that of emm genes. MATERIALS AND METHODSBacterial strains. The parent type 18 streptococcal strain 87-282 (designated 18-282) and its M-ne...

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Stent-graft infection may be a cause of unexplained endotension. Special culture techniques may be required to identify the infecting organism. Prophylactic antibiotics against skin organisms should be considered for all implantations and arterial diagnostic and therapeutic procedures traversing a stent-graft.