期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：20
页码：11578-11583
DOI：10.1073/pnas.96.20.11578
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mutants of Salmonella typhimurium lacking DNA adenine methylase are attenuated for virulence in BALB/c mice. LD50 values of a DNA adenine methylation (Dam)- mutant are at least 103- to 104-fold higher than those of the parental strain when administrated by oral or intraperitoneal routes. Dam- mutants are unable to proliferate in target organs but persist in low numbers in these locations. Efficient protection to challenge with the virulent parental strain is observed in mice infected with a Dam- mutant. Use of the ileal loop assay shows that Dam- mutants are less cytotoxic to M cells and fail to invade enterocytes. In the tissue culture model, lack of DNA adenine methylation causes reduced ability to invade nonphagocytic cells. In contrast, no effect is observed either in intracellular proliferation within nonphagocytic cells or in survival within macrophages. The invasion defect of Dam- mutants is correlated with a distinct pattern of secreted proteins, which is observed in both PhoP+ and PhoP- backgrounds. Altogether, our observations suggest a multifactorial role of Dam methylation in Salmonella virulence.
