Enterobacterial Common Antigen Mutants of Salmonella enterica Serovar Typhimurium Establish a Persistent Infection and Provide Protection against Subsequent Lethal Challenge
| Autor: | Jeremy J. Gilbreath, D. Scott Merrell, Mark J. Soloski, Paul D. Rick, Jennifer Colvocoresses Dodds, Eleanor S. Metcalf |
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| Rok vydání: | 2012 |
| Předmět: |
Salmonella typhimurium
Serotype Salmonella Virulence Factors Immunology Mutant Transferases (Other Substituted Phosphate Groups) Virulence medicine.disease_cause Microbiology Mice Bacterial Proteins Antigen medicine Animals Antigens Bacterial Salmonella Infections Animal Attenuated vaccine biology Genetic Complementation Test biology.organism_classification Survival Analysis Virology Mice Inbred C57BL Complementation Infectious Diseases Liver Salmonella enterica Microbial Immunity and Vaccines Female Mutant Proteins Parasitology Gene Deletion Spleen |
| Zdroj: | Infection and Immunity. 80:441-450 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.05559-11 |
| Popis: | Infection with Salmonella spp. is a significant source of disease globally. A substantial proportion of these infections are caused by Salmonella enterica serovar Typhimurium. Here, we characterize the role of the enterobacterial common antigen (ECA), a surface glycolipid ubiquitous among enteric bacteria, in S. Typhimurium pathogenesis. Construction of a defined mutation in the UDP- N -acetylglucosamine-1-phosphate transferase gene, wecA , in two clinically relevant strains of S. Typhimurium, TML and SL1344, resulted in strains that were unable to produce ECA. Loss of ECA did not affect the gross cell surface ultrastructure, production of lipopolysaccharide (LPS), flagella, or motility. However, the wecA mutant strains were attenuated in both oral and intraperitoneal mouse models of infection ( P < 0.001 for both routes of infection; log rank test), and virulence could be restored by complementation of the wecA gene in trans . Despite the avirulence of the ECA-deficient strains, the wecA mutant strains were able to persistently colonize systemic sites (spleen and liver) at moderate levels for up to 70 days postinfection. Moreover, immunization with the wecA mutant strains provided protection against a subsequent lethal oral or intraperitoneal challenge with wild-type S. Typhimurium. Thus, wecA mutant (ECA-negative) strains of Salmonella may be useful as live attenuated vaccine strains or as vehicles for heterologous antigen expression. |
| Databáze: | OpenAIRE |
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