Pseudomonas aeruginosa Oligoribonuclease Controls Tolerance to Polymyxin B by Regulating Pel Exopolysaccharide Production.
Antimicrob Agents Chemother
; 66(3): e0207221, 2022 03 15.
Article
en En
| MEDLINE
| ID: mdl-35007136
ABSTRACT
Polymyxins are considered as the last resort antibiotics to treat infections caused by multidrug-resistant Gram-negative pathogens. Pseudomonas aeruginosa is an opportunistic pathogen that causes various infections in humans. Proteins involved in lipopolysaccharide modification and maintaining inner and outer membrane integrities have been found to contribute to the bacterial resistance to polymyxins. Oligoribonuclease (Orn) is an exonuclease that regulates the homeostasis of intracellular (3'-5')-cyclic dimeric GMP (c-di-GMP), thereby regulating the production of extracellular polysaccharide in P. aeruginosa. Previously, we demonstrated that Orn affects the bacterial resistance to fluoroquinolone, ß-lactam and aminoglycoside antibiotics. In this study, we found that mutation of orn increased the bacterial survival following polymyxin B treatment in a wild-type P. aeruginosa strain PA14. Overexpression of c-di-GMP degradation enzymes in the orn mutant reduced the bacterial survival. By using a fluorescence labeled polymyxin B, we found that mutation of orn increased the bacterial surface bound polymyxin B. Deletion of the Pel synthesis genes or treatment with a Pel hydrolase reduced the surface bound polymyxin B and bacterial survival. We further demonstrated that Pel binds to extracellular DNA (eDNA), which traps polymyxin B and thus protects the bacterial cells. Collectively, our results revealed a novel defense mechanism against polymyxin in P. aeruginosa.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polimixina B
/
Pseudomonas aeruginosa
Límite:
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2022
Tipo del documento:
Article
País de afiliación:
China