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Role of Base Excision Repair in Listeria monocytogenes DNA Stress Survival During Infections.
Zhang, Juan; Wang, Shuyi; Abee, Tjakko; van der Veen, Stijn.
Affiliation
  • Zhang J; Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China.
  • Wang S; Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China.
  • Abee T; Food Microbiology, Wageningen University & Research, Wageningen, The Netherlands.
  • van der Veen S; Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China.
J Infect Dis ; 223(4): 721-732, 2021 02 24.
Article in En | MEDLINE | ID: mdl-32644146
BACKGROUND: Base excision repair (BER), consisting mostly of lesion-specific DNA glycosylases and apurinic/apyrimidinic (AP) endonucleases, is one of the most important DNA repair mechanisms for repair of single nucleobase lesions generated by reactive oxygen and nitrogen species as part of an immune response against bacterial infections. However, few studies have addressed the contribution of BER to bacterial virulence and Listeria monocytogenes BER has thus far remained completely uncharacterized. METHODS: Analysis of the L. monocytogenes EGDe genome identified 7 DNA glycosylases (MutM, MutY, Nth, Tag, Mpg, Ung, and Ung2) and 2 apurinic/apyrimidinic endonucleases (Xth and Nfo) as part of BER. Markerless in-frame deletion mutants were generated for all 9 genes, and mutants were tested for DNA damage survival, mutagenesis, and the ability to colonize a mouse model of infection. RESULTS: Distinct lesion-specific phenotypes were identified for all deletion mutants. Importantly, the Δnth, ΔmutY, and Δnfo mutants were significantly attenuated for virulence in the mouse model and showed much lower colonization of the liver and spleen or were unable to compete with the wild-type strain during in vivo competition assays. CONCLUSIONS: Our results highlight the importance of BER for L. monocytogenes virulence and survival of DNA-damaging insults during host colonization.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA, Bacterial / DNA Repair / Listeriosis / Listeria monocytogenes / Macrophages Limits: Animals / Female / Humans Language: En Journal: J Infect Dis Year: 2021 Document type: Article Affiliation country: China Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA, Bacterial / DNA Repair / Listeriosis / Listeria monocytogenes / Macrophages Limits: Animals / Female / Humans Language: En Journal: J Infect Dis Year: 2021 Document type: Article Affiliation country: China Country of publication: United States