title: Epistatic roles for Pseudomonas aeruginosa MutS and DinB (DNA Pol IV) in coping with reactive oxygen species-induced DNA damage.
abstract: Pseudomonas aeruginosa is especially adept at colonizing the airways of individuals afflicted with the autosomal recessive disease cystic fibrosis (CF). CF patients suffer from chronic airway inflammation, which contributes to lung deterioration. Once established in the airways, P. aeruginosa continuously adapts to the changing environment, in part through acquisition of beneficial mutations via a process termed pathoadaptation. MutS and DinB are proposed to play opposing roles in P. aeruginosa pathoadaptation: MutS acts in replication-coupled mismatch repair, which acts to limit spontaneous mutations; in contrast, DinB (DNA polymerase IV) catalyzes error-prone bypass of DNA lesions, contributing to mutations. As part of an ongoing effort to understand mechanisms underlying P. aeruginosa pathoadaptation, we characterized hydrogen peroxide (H(2)O(2))-induced phenotypes of isogenic P. aeruginosa strains bearing different combinations of mutS and dinB alleles. Our results demonstrate an unexpected epistatic relationship between mutS and dinB with respect to H(2)O(2)-induced cell killing involving error-prone repair and/or tolerance of oxidized DNA lesions. In striking contrast to these error-prone roles, both MutS and DinB played largely accurate roles in coping with DNA lesions induced by ultraviolet light, mitomycin C, or 4-nitroquinilone 1-oxide. Models discussing roles for MutS and DinB functionality in DNA damage-induced mutagenesis, particularly during CF airway colonization and subsequent P. aeruginosa pathoadaptation are discussed.
authors.affiliation: Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, United States of America.
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sanders
authors.forename: Babho
authors.initials: B
authors.lastname: Devadoss
authors.forename: Geraldine V
authors.initials: GV
authors.lastname: Raja
authors.forename: Jaime
authors.initials: J
authors.lastname: O'Connor
authors.forename: Shengchang
authors.initials: S
authors.lastname: Su
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wozniak
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hassett
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Berdis
authors.forename: Mark D
authors.initials: MD
authors.lastname: Sutton
mesh_terms: D002384:Catalysis; D004249:DNA Damage; D004843:Epistasis, Genetic; D006861:Hydrogen Peroxide / Q000378:metabolism; D051719:MutS DNA Mismatch-Binding Protein / Q000502:physiology*; D016296:Mutagenesis; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D051719:MutS DNA Mismatch-Binding Protein