Chromosomal cephalosporinase in Enterobacter hormaechei as an ancestor of ACT-1 plasmid-mediated AmpC β-lactamase

Abstract

In this study of the diversity of AmpC b-lactamase in clinical isolates of Enterobacter spp., a strain was found carrying the plasmid-mediated AmpC b-lactamase ACT-1 gene on its chromosome. The strain was identified as Enterobacter hormaechei using phylogenetic analysis of 16S rRNA and hsp60 genes. In addition, the species was confirmed by DNA-DNA hybridization. The genetic environment of the bla ACT-1 gene was characterized, including the ampR and ampG genes, using a two-step PCR. The amino acid sequences of AmpR at serine 35, arginine 86, glycine 102, aspartic acid 135 and tyrosine 264 were conserved. Measurement of the transcription level of the bla ACT-1 gene using real-time quantitative PCR showed that it increased 1.98-fold following cefoxitin induction. These results suggest that the plasmid-mediated bla ACT-1 gene originated from the chromosome of E. hormaechei.

The sentinel role of peptidoglycan recycling in the β-lactam resistance of the Gram-negative Enterobacteriaceae and Pseudomonas aeruginosa

“…The AmpC β-lactamase is a member of the class C serine-dependent β-lactamase family. It was once a chromosomal enzyme of the Enterobacteriaceae but now is increasingly found as constitutively expressed from a plasmid [4, 5]. The proliferation of several different β-lactamases, each with the ability to confer resistance to both the cephalosporin and carbapenem β-lactam structures [6, 7], is foundational to the concern that an era of untreatable bacterial infection is nigh [8].…”

Enterobacter cloacae Complex: Clinical Impact and Emerging Antibiotic Resistance

“…ESBLs and AmpC-type cephalo sporinases that can hydrolyze thirdgeneration cephalosporins such as cefotaxime or ceftazidime confer resistance more frequently to E. cloacae strains isolated in patients who previously received these antibiotics [29]. E. hormaechei is also an AmpC producer, and it has been recently demonstrated that the plasmid-mediated AmpC bla ACT-1 gene originated from the chromosome of E. hormaechei, which was previously believed to derive from E. cloacae [57].…”

“…In accordance with this observation, the use of cefepime increased the sensitivity of the DDST for the detection of ESBLs in Enterobacter from 16 to 61% when the disks were applied at the standard distance of 30 mm from clavulanate, and from 71 to 90% with closer application of the disks [61]. [14,16,63,64] VEB, GES/IBC, KPC E. cloacae [62,65,80,81,83,84,116] NMC-A, IMI-1, IMI-2 E. cloacae, Enterobacter asburiae [74][75][76][77][78][79]82] Ambler class B VIM E. cloacae, Enterobacter ludwigii [55,89,92] IMP, NDM-1 E. cloacae [86][87][88]90,91,96,97] Ambler class C Amp-C, ACT-1 E. cloacae, E. asburiae, E. hormaechei, Enterobacter kobei [57,113] Ambler class D OXA-48 E. cloacae [98,101] Fluoroquinolones Plasmid-mediated quinolone resistance Acetyltransferase AAC(6´)-Ib-cr E. cloacae [108,109,111,116] Qnr-mediated topoisom protection…”

ACT-107, a novel variant of AmpC β-lactamase from Enterobacter huaxiensis isolated from Neotropical leaf frog (Phyllomedusa distincta) inhabiting the Brazilian Atlantic Forest

“…Distinguishing β-lactamases in Enterobacterales has epidemiological significance. In this regard, some studies have demonstrated the contribution of Kluyvera, Citrobacter , and Enterobacter species to the recruitment and dissemination of plasmid-mediated extended-spectrum β-lactamases and/or AmpC β-lactamases [ 8 , [33] , [34] , [35] , [36] ]. Specifically, the presence of AmpC in plasmids has contributed to the rapid spread of this mechanism of resistance.…”

“…Therefore, knowing the distribution of ACT-type β-lactamases in Enterobacter species will allow inferences regarding the putative origin of pAmpCs that could emerge in clinically relevant pathogens. In this respect, the chromosomally encoded AmpC β-lactamase reported in E. hormaechei has been suggested as the putative progenitor of the pACT-1 found in Klebsiella pneumoniae [ 34 , 37 ].…”