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Nonpolar inactivation of the hypervariable streptococcal inhibitor of complement gene (sic) in serotype M1
1Institute for the Study of Human Bacterial Pathogenesis, Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Group A Streptococcus (GAS) is a human pathogen that commonly infects the upper respiratory tract. GAS serotype M1 strains are frequently isolated from human infections and contain the gene encoding the hypervariable streptococcal inhibitor of complement protein (Sic). It was recently shown that Sic variants were rapidly selected on mucosal surfaces in epidemic waves caused by M1 strains, an observation suggesting that Sic participates in host-pathogen interactions on the mucosal surface (N. P. Hoe, K. Nakashima, S. Lukomski, 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 spectinomycin resistance cassette was used to inactivate the sic gene in an M1 GAS strain. The isogenic Sic-negative mutant strain was significantly (P < 0.019) impaired in ability to colonize the mouse mucosal surface after intranasal infection. These results support the hypothesis that the predominance of M1 strains in human infections is related, in part, to a Sic-mediated enhanced colonization ability.
Insights
Group A Streptococcus (GAS) M1 strains use the streptococcal inhibitor of complement protein (Sic) to colonize mucosal surfaces. Sic-negative GAS strains showed impaired colonization, supporting Sic's role in M1 strain infections.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Group A Streptococcus (GAS) is a significant human pathogen, frequently causing upper respiratory tract infections.
- M1 serotype GAS strains are prevalent in human infections and possess the gene for streptococcal inhibitor of complement protein (Sic).
- Previous research indicated rapid selection of Sic variants on mucosal surfaces during M1 strain epidemics, suggesting Sic involvement in host-pathogen interactions.
Purpose of the Study:
- To investigate the role of the streptococcal inhibitor of complement protein (Sic) in the colonization ability of Group A Streptococcus (GAS) M1 strains.
- To determine if Sic contributes to the predominance of M1 GAS strains in human infections.
Main Methods:
- Utilized a novel nonpolar mutagenesis technique with a spectinomycin resistance cassette to create a sic gene knockout in an M1 GAS strain.
- Generated an isogenic Sic-negative mutant strain of M1 GAS.
- Assessed the colonization ability of the wild-type and mutant strains on mouse mucosal surfaces following intranasal infection.
Main Results:
- The Sic-negative mutant strain exhibited a statistically significant impairment (P < 0.019) in its ability to colonize the mouse mucosal surface.
- This finding demonstrates a direct impact of the sic gene on bacterial colonization efficiency.
Conclusions:
- The results support the hypothesis that the streptococcal inhibitor of complement protein (Sic) plays a crucial role in the colonization of mucosal surfaces by M1 GAS strains.
- Sic-mediated enhanced colonization ability is a contributing factor to the epidemiological success and predominance of M1 GAS strains in human infections.