Significant Impact of AcrB Amino Acid Polymorphism at Residue 716 on Susceptibility to Tigecycline and Other Antibiotics in Klebsiella pneumoniae.
ACS Infect Dis
; 10(2): 541-552, 2024 02 09.
Article
em En
| MEDLINE
| ID: mdl-38181222
ABSTRACT
AcrAB-TolC is a multidrug RND-type efflux pump that is widespread in Gram-negative bacteria. As the substrate-binding subunit, AcrB was shown to modulate antimicrobial resistance in Escherichia coli, but the influence of AcrB mutation on Klebsiella pneumoniae, a major clinical pathogen, has not been well-studied. The finding of an R716L mutation in AcrB in a clinical tigecycline-nonsusceptible K. pneumoniae S1 strain inspired us to probe the role of AcrB residue 716 in antimicrobial resistance. This residue was subsequently subjected to saturation mutagenesis, followed by antibiotic susceptibility tests, survival assays, and antibiotic accumulation assays, showing strong influences of AcrB mutation on antimicrobial resistance. In particular, resistance levels to azithromycin, tetracycline, tigecycline, and cefoxitin were significantly changed by AcrB mutation at residue 716. Mutations to charged residues, polar residues, and residues that disrupt secondary structures have particularly reduced the antimicrobial susceptibility of bacteria, except for azithromycin, and the impact is not due to the abolishment of the efflux function of the pump. Therefore, it is concluded that residue 716 is an important residue that significantly influences antimicrobial resistance in K. pneumoniae, adding to our understanding of antimicrobial resistance mechanisms in this key clinical pathogen.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Escherichia coli
/
Minociclina
Idioma:
En
Revista:
ACS Infect Dis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China