Cefazolin and imipenem enhance AmpC expression and resistance in NagZ-dependent manner in Enterobacter cloacae complex

Bibliographic Details
Title: Cefazolin and imipenem enhance AmpC expression and resistance in NagZ-dependent manner in Enterobacter cloacae complex
Authors: Xianggui Yang, Zhenguo Wang, Mingquan Liu, Xuejing Yu, Yuanxiu Zhong, Fuying Wang, Ying Xu
Source: BMC Microbiology, Vol 22, Iss 1, Pp 1-11 (2022)
Publisher Information: BMC, 2022.
Publication Year: 2022
Collection: LCC:Microbiology
Subject Terms: Cefazolin, Imipenem, AmpC, NagZ, Enterobacter cloacae complex, Microbiology, QR1-502
More Details: Abstract Background Enterobacter cloacae complex (ECC) is a common opportunistic pathogen and is responsible for causing various infections in humans. Owing to its inducible chromosomal AmpC β-lactamase (AmpC), ECC is inherently resistant to the 1st- and 2nd- generation cephalosporins. However, whether β-lactams antibiotics enhance ECC resistance remains unclear. Results In this study, we found that subinhibitory concentrations (SICs) of cefazolin (CFZ) and imipenem (IMP) can advance the expression of AmpC and enhance its resistance towards β-lactams through NagZ in Enterobacter cloacae (EC). Further, AmpC manifested a substantial upregulation in EC in response to SICs of CFZ and IMP. In nagZ knockout EC (ΔnagZ), the resistance to β-lactam antibiotics was rather weakened and the effect of CFZ and IMP on AmpC induction was completely abrogated. NagZ ectopic expression can rescue the induction effects of CFZ and IMP on AmpC and increase ΔnagZ resistance. More importantly, CFZ and IMP have the potential to induce the expression of AmpR's target genes in a NagZ-dependent manner. Conclusions Our findings suggest that NagZ is a critical determinant for CFZ and IMP to promote AmpC expression and resistance and that CFZ and IMP should be used with caution since they may aggravate ECC resistance. At the same time, this study further improves our understanding of resistance mechanisms in ECC.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1471-2180
Relation: https://doaj.org/toc/1471-2180
DOI: 10.1186/s12866-022-02707-7
Access URL: https://doaj.org/article/d0a10c29dfa14460a3f70f4590528fe0
Accession Number: edsdoj.0a10c29dfa14460a3f70f4590528fe0
Database: Directory of Open Access Journals
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More Details
ISSN:14712180
DOI:10.1186/s12866-022-02707-7
Published in:BMC Microbiology
Language:English