An Acinetobacter baumannii, Zinc-Regulated Peptidase Maintains Cell Wall Integrity during Immune-Mediated Nutrient Sequestration.
Cell Rep
; 26(8): 2009-2018.e6, 2019 02 19.
Article
em En
| MEDLINE
| ID: mdl-30784584
ABSTRACT
Acinetobacter baumannii is an important nosocomial pathogen capable of causing wound infections, pneumonia, and bacteremia. During infection, A. baumannii must acquire Zn to survive and colonize the host. Vertebrates have evolved mechanisms to sequester Zn from invading pathogens by a process termed nutritional immunity. One of the most upregulated genes during Zn starvation encodes a putative cell wall-modifying enzyme which we named ZrlA. We found that inactivation of zrlA diminished growth of A. baumannii during Zn starvation. Additionally, this mutant strain displays increased cell envelope permeability, decreased membrane barrier function, and aberrant peptidoglycan muropeptide abundances. This altered envelope increases antibiotic efficacy both in vitro and in an animal model of A. baumannii pneumonia. These results establish ZrlA as a crucial link between nutrient metal uptake and cell envelope homeostasis during A. baumannii pathogenesis, which could be targeted for therapeutic development.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Zinco
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Metaloendopeptidases
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Parede Celular
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Pneumonia Bacteriana
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Acinetobacter baumannii
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article