title: Bacterial hypermutation: clinical implications.
abstract: Heritable hypermutation in bacteria is mainly due to alterations in the methyl-directed mismatch repair (MMR) system. MMR-deficient strains have been described from several bacterial species, and all of the strains exhibit increased mutation frequency and recombination, which are important mechanisms for acquired drug resistance in bacteria. Antibiotics select for drug-resistant strains and refine resistance determinants on plasmids, thus stimulating DNA recombination via the MMR system. Antibiotics can also act as indirect promoters of antibiotic resistance by inducing the SOS system and certain error-prone DNA polymerases. These alterations have clinical consequences in that efficacious treatment of bacterial infections requires high doses of antibiotics and/or a combination of different classes of antimicrobial agents. There are currently few new drugs with low endogenous resistance potential, and the development of such drugs merits further research.
authors.affiliation: Equipe Microbiologie, UPRES-EA 1254, Pontchaillou Teaching Hospital and Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, Université Européenne de Bretagne, 2 avenue du Professeur Léon Bernard, 35043 Rennes, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Jolivet-Gougeon
authors.affiliation: Department of Urology, Jahn Ferenc Del-Pesti Hospital, Koves ut 2, 1204 Budapest, Hungary.
authors.forename: Bela
authors.initials: B
authors.lastname: Kovacs
authors.affiliation: Equipe Microbiologie, UPRES-EA 1254, Pontchaillou Teaching Hospital and Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, Université Européenne de Bretagne, 2 avenue du Professeur Léon Bernard, 35043 Rennes, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Le Gall-David
authors.affiliation: Equipe Microbiologie, UPRES-EA 1254, Pontchaillou Teaching Hospital and Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, Université Européenne de Bretagne, 2 avenue du Professeur Léon Bernard, 35043 Rennes, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Bars
authors.affiliation: Equipe Microbiologie, UPRES-EA 1254, Pontchaillou Teaching Hospital and Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, Université Européenne de Bretagne, 2 avenue du Professeur Léon Bernard, 35043 Rennes, France.
authors.forename: Latifa
authors.initials: L
authors.lastname: Bousarghin
authors.affiliation: Equipe Microbiologie, UPRES-EA 1254, Pontchaillou Teaching Hospital and Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, Université Européenne de Bretagne, 2 avenue du Professeur Léon Bernard, 35043 Rennes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Bonnaure-Mallet
authors.affiliation: Service d'Urologie, CHU Pontchaillou, 2 rue Henri Le Guilloux, 35033 Rennes cedex 9, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lobel
authors.affiliation: Service d'Urologie, CHU Pontchaillou, 2 rue Henri Le Guilloux, 35033 Rennes cedex 9, France.
authors.forename: François
authors.initials: F
authors.lastname: Guillé
authors.affiliation: Service de Bactériologie-Virologie-Hygiène, CHU Henri-Mondor, 51 avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France.
authors.forename: Claude-James
authors.initials: CJ
authors.lastname: Soussy
authors.affiliation: Department of Urology, Jahn Ferenc Del-Pesti Hospital, Koves ut 2, 1204 Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Tenke
mesh_terms: D001419:Bacteria / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D003550:Cystic Fibrosis / Q000382:microbiology; D053843:DNA Mismatch Repair / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005517:Foodborne Diseases / Q000382:microbiology; D005798:Genes, Bacterial; D006801:Humans; D020071:Interspersed Repetitive Sequences; D009154:Mutation; D010641:Phenotype; D039002:Prophages / Q000235:genetics; D011995:Recombination, Genetic; D013014:SOS Response, Genetics / Q000235:genetics; D014552:Urinary Tract Infections / Q000382:microbiology; D014774:Virulence / Q000235:genetics