An essential role for DNA adenine methylation in bacterial virulence
An essential role for DNA adenine methylation in bacterial virulence
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DOI：
10.1126/science.284.5416.967
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发表时间：
1999-05-07
期刊：
影响因子：
56.9
通讯作者：
Mahan, MJ
中科院分区：
文献类型：
--
作者：
Heithoff, DM;Sinsheimer, RL;Mahan, MJ
缺乏 DNA 腺嘌呤甲基化酶 (Dam) 的鼠伤寒沙门氏菌完全擅长粘膜部位的定植，但在更深组织部位的定植方面表现出严重缺陷。这些 Dam(-) 突变体完全无毒，并且作为针对鼠伤寒的活疫苗是有效的。 Dam 调节至少 20 个已知在感染过程中诱导的基因的表达；这些基因的一个子集属于由 PhoP 全局毒力调节因子激活的基因。 PhoP 反过来影响特定基因组位点的 Dam 甲基化，DNA 甲基化模式的改变证明了这一点。 Dam 抑制剂可能具有广泛的抗菌作用，并且这些病原体的 Dam 衍生物可以用作减毒活疫苗。
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.