An Essential Role for DNA Adenine Methylation in Bacterial Virulence

作者: Douglas M Heithoff , Robert L Sinsheimer , David A Low , Michael J Mahan

DOI: 10.1126/SCIENCE.284.5416.967

关键词: GeneticsMutationVirulenceBiologyDNA methylationAttenuated vaccineMicrobiologyMethylationGeneMethyltransferaseDNAMultidisciplinary

摘要: Salmonella typhimurium lacking DNA adenine methylase (Dam) were fully proficient in colonization of mucosal sites but showed severe defects deeper tissue sites. These Dam- mutants totally avirulent and effective as live vaccines against murine typhoid fever. Dam regulated the expression at least 20 genes known to be induced during infection; a subset these are among those activated by PhoP global virulence regulator. PhoP, turn, affected methylation specific genomic sites, evidenced alterations patterns. inhibitors likely have broad antimicrobial action, derivatives pathogens may serve attenuated vaccines.

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