Hypermutation in Pathogenic Bacteria

Bucci, Cecilia; Lavitola, Alfredo; Salvatore, Paola; Giudice, Luigi Del; Massardo, Domenica Rita; Bruni, Carmelo B.; Alifano, Pietro

doi:10.1016/s1097-2765(00)80471-2

Cited by 118 publications

(29 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, 39% (21 of 54) of mutator phenotypes are linked to defects in the neisserial DNA mismatch repair system. Conflicting results have been reported on the role of Dam methylase in the neisserial mismatch repair system (11,13). All 95 menA isolates in this collection lacked Dam activity, including the 40 isolates displaying wild-type mutability (data not shown).…”

Section: Many Mutator Isolates Possess Defects In the Postmentioning

confidence: 71%

See 1 more Smart Citation

Mutator clones of Neisseria meningitidis in epidemic serogroup A disease

Richardson

Popović

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

155

169

View full text Add to dashboard Cite

Serogroup A Neisseria meningitidis has repeatedly caused widespread epidemics of meningitis and septicemia throughout the 20th century. Recently, in a limited collection of strains, epidemic serogroup A isolates were found to have elevated mutation rates that was caused by defects in mismatch repair pathways. To ascertain the role of these mutators in the epidemic spread of this serogroup, the prevalence of hypermutability in a collection of 95 serogroup A N. meningitidis invasive isolates was determined. Overall mutability in Neisseriae can be described by measuring both missense mutation rates as well as phase variation frequencies of ''contingency loci.'' Fifty-seven percent of serogroup A isolates possessed elevated mutability, which could be divided into two classes: intermediate and high level. Eleven of 20 high-level mutators, with phase variation rates >100-fold higher than wildtype isolates, were defective in mismatch repair. Ten of the 34 intermediate mutators possessing >10-fold increases in phase variation rates could be partially complemented by a wild-type mutL allele. A high prevalence of mutators in epidemic isolates indicates that hypermutability may play a major role in the transmission of this pathogen. The added diversity derived from increased phase variation rates may allow fixation of mutator alleles more frequently during epidemic spread.meningitis ͉ evolution ͉ mismatch repair ͉ transmission ͉ virulence

show abstract

Section: Many Mutator Isolates Possess Defects In the Postmentioning

confidence: 71%

“…Recently, N. meningitidis isolates with elevated rates of phase variation have been described (11)(12)(13). Particularly, strains defective in postreplicative mismatch repair possess phase variation rates greater than 100-fold higher than that of wild-type N. meningitidis.…”

mentioning

confidence: 99%

Mutator clones of Neisseria meningitidis in epidemic serogroup A disease

Richardson

Popović

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

155

169

View full text Add to dashboard Cite

show abstract

“…These results may account for the observation that some natural bacterial isolates, such as those of Pseudomonas aeruginosa found in the lungs of cystic fibrosis patients, have a strong mutator phenotype. It may also inspire studies on emerging pathogenicity and drug resistance in microorganisms (2,4,21,22), as well as assisting studies on the somatic evolution of malignant mutator tumor cells (23).…”

Section: Figmentioning

confidence: 99%

Costs and Benefits of High Mutation Rates: Adaptive Evolution of Bacteria in the Mouse Gut

Giraud

Matić

Tenaillon

et al. 2001

Science

453

446

View full text Add to dashboard Cite

We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.

show abstract

“…catalytic activity has not yet been shown Dnmt3a (mouse) CG 908 cytosine-C5 also methylates non-CG sites with high activity [136,206] methylation plays a role in the segregation of the E. coli chromosome. Despite these important functions, dam methylation is not essential in E. coli, but it is involved in the pathogenicity of different bacteria like Bordetella pertussis, [28] E. coli, [29] Salmonella thyphimurium, [30±33] and Neisseria meningitidis, [34] a fact that suggests that inhibitors of dam methylation might be effective as antibacterial drugs.…”

Section: The Role Of Dna Methylation In Prokaryotesmentioning

confidence: 99%

Beyond Watson and Crick: DNA Methylation and Molecular Enzymology of DNA Methyltransferases

2002

View full text Add to dashboard Cite

DNA methyltransferases catalyze the transfer of a methyl group from S-adenosyl-L-methionine to cytosine or adenine bases in DNA. These enzymes challenge the Watson/Crick dogma in two instances: 1) They attach inheritable information to the DNA that is not encoded in the nucleotide sequence. This so-called epigenetic information has many important biological functions. In prokaryotes, DNA methylation is used to coordinate DNA replication and the cell cycle, to direct postreplicative mismatch repair, and to distinguish self and nonself DNA. In eukaryotes, DNA methylation contributes to the control of gene expression, the protection of the genome against selfish DNA, maintenance of genome integrity, parental imprinting, X-chromosome inactivation in mammals, and regulation of development. 2) The enzymatic mechanism of DNA methyltransferases is unusual, because these enzymes flip their target base out of the DNA helix and, thereby, locally disrupt the B-DNA helix. This review describes the biological functions of DNA methylation in bacteria, fungi, plants, and mammals. In addition, the structures and mechanisms of the DNA methyltransferases, which enable them to specifically recognize their DNA targets and to induce such large conformational changes of the DNA, are discussed.

show abstract

Hypermutation in Pathogenic Bacteria

Cited by 118 publications

References 37 publications

Mutator clones of Neisseria meningitidis in epidemic serogroup A disease

Mutator clones of Neisseria meningitidis in epidemic serogroup A disease

Costs and Benefits of High Mutation Rates: Adaptive Evolution of Bacteria in the Mouse Gut

Beyond Watson and Crick: DNA Methylation and Molecular Enzymology of DNA Methyltransferases

Contact Info

Product

Resources

About