An interstrand DNA crosslink glycosylase aids Acinetobacter baumannii pathogenesis.
Proc Natl Acad Sci U S A
; 121(27): e2402422121, 2024 Jul 02.
Article
em En
| MEDLINE
| ID: mdl-38923984
ABSTRACT
Maintenance of DNA integrity is essential to all forms of life. DNA damage generated by reaction with genotoxic chemicals results in deleterious mutations, genome instability, and cell death. Pathogenic bacteria encounter several genotoxic agents during infection. In keeping with this, the loss of DNA repair networks results in virulence attenuation in several bacterial species. Interstrand DNA crosslinks (ICLs) are a type of DNA lesion formed by covalent linkage of opposing DNA strands and are particularly toxic as they interfere with replication and transcription. Bacteria have evolved specialized DNA glycosylases that unhook ICLs, thereby initiating their repair. In this study, we describe AlkX, a DNA glycosylase encoded by the multidrug resistant pathogen Acinetobacter baumannii. AlkX exhibits ICL unhooking activity similar to that of its Escherichia coli homolog YcaQ. Interrogation of the in vivo role of AlkX revealed that its loss sensitizes cells to DNA crosslinking and impairs A. baumannii colonization of the lungs and dissemination to distal tissues during pneumonia. These results suggest that AlkX participates in A. baumannii pathogenesis and protects the bacterium from stress conditions encountered in vivo. Consistent with this, we found that acidic pH, an environment encountered during host colonization, results in A. baumannii DNA damage and that alkX is induced by, and contributes to, defense against acidic conditions. Collectively, these studies reveal functions for a recently described class of proteins encoded in a broad range of pathogenic bacterial species.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Acinetobacter baumannii
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DNA Glicosilases
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article