Publication Date:
1999-05-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heithoff, D M -- Sinsheimer, R L -- Low, D A -- Mahan, M J -- AI23348/AI/NIAID NIH HHS/ -- AI36373/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 May 7;284(5416):967-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320378" target="_blank"〉PubMed〈/a〉
Keywords:
Adenine/metabolism
;
Animals
;
Bacterial Proteins/metabolism
;
*Bacterial Vaccines
;
*DNA Methylation
;
DNA, Bacterial/metabolism
;
Gene Expression Regulation, Bacterial
;
Genes, Bacterial
;
Lethal Dose 50
;
Methylation
;
Mice
;
Mice, Inbred BALB C
;
Mutation
;
Peyer's Patches/microbiology
;
Salmonella Infections, Animal/immunology/*microbiology/prevention & control
;
Salmonella typhimurium/*enzymology/genetics/immunology/*pathogenicity
;
Site-Specific DNA-Methyltransferase (Adenine-Specific)/antagonists &
;
inhibitors/genetics/*metabolism
;
Vaccines, Attenuated
;
Virulence/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
