Enterobacterial common antigen mutants of Salmonella enterica serovar Typhimurium establish a persistent infection and provide protection against subsequent lethal challenge.

Abstract

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.

• Authors: Jeremy J Gilbreath, Jennifer Colvocoresses Dodds, Paul D Rick, Mark J Soloski, D Scott Merrell, Eleanor S Metcalf
• Journal: Infection and immunity (Infect Immun) Vol. 80 Issue 1 Pg. 441-50 (Jan 2012) ISSN: 1098-5522 [Electronic] United States
• PMID: 22025511 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• Mutant Proteins
• Virulence Factors
• enterobacterial common antigen
• Transferases (Other Substituted Phosphate Groups)
• UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase

Topics

• Animals
• Antigens, Bacterial (genetics, metabolism)
• Bacterial Proteins (genetics)
• Female
• Gene Deletion
• Genetic Complementation Test
• Liver (microbiology)
• Mice
• Mice, Inbred C57BL
• Mutant Proteins (genetics)
• Salmonella Infections, Animal (microbiology, mortality, pathology)
• Salmonella typhimurium (genetics, immunology, pathogenicity)
• Spleen (microbiology)
• Survival Analysis
• Transferases (Other Substituted Phosphate Groups) (genetics)
• Virulence Factors (genetics, metabolism)