An essential role for DNA adenine methylation in bacterial virulence

被引:397
作者
Heithoff, DM [1 ]
Sinsheimer, RL [1 ]
Low, DA [1 ]
Mahan, MJ [1 ]
机构
[1] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA
关键词
D O I
10.1126/science.284.5416.967
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Salmonella typhimurium lacking DNA adenine methylase (Dam) were fully proficient in colonization of mucosal sites but showed severe defects in colonization of deeper tissue sites. These Dam(-) mutants were totally avirulent and were effective as live vaccines against murine typhoid fever. Dam regulated the expression of at least 20 genes known to be induced during infection; a subset of these genes are among those activated by the PhoP global virulence regulator. PhoP, in turn, affected Dam methylation at specific genomic sites, as Evidenced by alterations in DNA methylation patterns. Dam inhibitors are likely to have broad antimicrobial action, and Dam- derivatives of these pathogens may serve as Live attenuated vaccines.
引用
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页码:967 / 970
页数:4
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