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oai:repisalud.isciii.es:20.500.12105/238302024-11-29T06:20:18Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Barceló, Isabel María author Escobar-Salom, Maria author Jordana-Lluch, Elena author Torrens, Gabriel author Oliver, Antonio author Juan, Carlos author 2024-01-02 Enterobacter cloacae starred different pioneer studies that enabled the development of a widely accepted model for the peptidoglycan metabolism-linked regulation of intrinsic class C cephalosporinases, highly conserved in different Gram-negatives. However, some mechanistic and fitness/virulence-related aspects of E. cloacae choromosomal AmpC-dependent resistance are not completely understood. The present study including knockout mutants, β-lactamase cloning, gene expression analysis, characterization of resistance phenotypes, and the Galleria mellonella infection model fills these gaps demonstrating that: (i) AmpC enzyme does not show any collateral activity impacting fitness/virulence; (ii) AmpC hyperproduction mediated by ampD inactivation does not entail any biological cost; (iii) alteration of peptidoglycan recycling alone or combined with AmpC hyperproduction causes no attenuation of E. cloacae virulence in contrast to other species; (iv) derepression of E. cloacae AmpC does not follow a stepwise dynamics linked to the sequential inactivation of AmpD amidase homologues as happens in Pseudomonas aeruginosa; (v) the enigmatic additional putative AmpC-type β-lactamase generally present in E. cloacae does not contribute to the classical cephalosporinase hyperproduction-based resistance, having a negligible impact on phenotypes even when hyperproduced from multicopy vector. This study reveals interesting particularities in the chromosomal AmpC-related behavior of E. cloacae that complete the knowledge on this top resistance mechanism. Barceló IM, Escobar-Salom M, Jordana-Lluch E, Torrens G, Oliver A, Juan C. Filling knowledge gaps related to AmpC-dependent β-lactam resistance in Enterobacter cloacae. Sci Rep. 2024 Jan 2;14(1):189. 10.1038/s41598-023-50685-1 10.1038/s41598-023-50685-1 2045-2322 Scientific reports https://hdl.handle.net/20.500.13003/20131 38167986 https://hdl.handle.net/20.500.12105/23830 Filling knowledge gaps related to AmpC-dependent β-lactam resistance in Enterobacter cloacae