Active and passive immunizations with the streptococcal esterase Sse protect mice against subcutaneous infection with group A streptococci.
The human pathogen group A Streptococcus (GAS) produces many secreted proteins that play important roles in GAS pathogenesis, including hydrolases that degrade proteins and nucleic acids. This study targets another kind of hydrolase, carboxylic esterase, with the objectives of identifying GAS esterase and determining whether it is a protective antigen. The putative esterase gene SPy1718 was cloned, and the recombinant protein (Sse) was prepared. Sse was detected in GAS culture supernatant, and patients with streptococcal pharyngitis seroconverted to Sse, indicating that Sse was produced in vivo and in vitro. Sse hydrolyzes p-nitrophenyl butyrate, and the residue (178)Ser is critical for this esterase activity. There are two Sse variant complexes according to the available genome databases, consistent with the previous finding of two antigenic Sse variants. Complex I includes serotypes M1, M2, M3, M5, M6, M12, and M18, whereas M4, M28, and M49 belong to complex II. Sse variants share >98% identity in amino acid sequence within each complex but have about 37% variation between the two groups. Active immunization with M1 Sse significantly protects mice against lethal subcutaneous infection with virulent M1 and M3 strains and inhibits GAS invasion of mouse skin tissue. Passive immunization with anti-Sse antiserum also significantly protects mice against subcutaneous GAS infection, indicating that the protection is mediated by Sse-specific antibodies. The results suggest that Sse plays an important role in tissue invasion and is an antigen protective in subcutaneous infection against GAS strains of more than one serotype.
Liu
Mengyao
M
Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
Zhu
Hui
H
Zhang
Jinlian
J
Lei
Benfang
B
D000818:Animals; D021461:Animals, Outbred Strains; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D007116:Immunization, Passive; D007279:Injections, Subcutaneous; D051379:Mice; D010612:Pharyngitis / Q000276:immunology / Q000382:microbiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012703:Serotyping; D017192:Skin Diseases, Bacterial / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D013297:Streptococcus pyogenes / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
D011994:Recombinant Proteins; D022541:Streptococcal Vaccines; D003546:Cysteine Endopeptidases; C042477:streptopain