Abstract
The emergence of tet(X) and carbapenemase genes in Enterobacterales pose significant challenges to the treatment of infectious diseases. Convergence of these two categories of genes in an individual pathogen would deteriorate the antimicrobial resistance (AMR) crisis furthermore. Here, tigecycline-resistant Enterobacterales strains were isolated and detected with carbapenemase genes, characterized by antimicrobial susceptibility testing, PCR, conjugation assay, whole genome sequencing, and bioinformatics analysis. Three tigecycline-resistant isolates consisting of one plasmid-mediated tet(X4)-bearing Escherichia fergusonii and two chromosomal tet(X6)-bearing Proteus cibarius were recovered from chicken feces. The tet(X4) was located on a conjugative IncX1 plasmid pHNCF11W-tetX4 encoding the identical structure as reported tet(X4)-bearing IncX1 plasmids in Escherichia coli. Among two P. cibarius strains, tet(X6) was located on two similar chromosomal MDR regions with genetic contexts IS26-aac(3)-IVa-aph(4)-Ia-ISEc59-tnpA-tet(X6)-orf-orf-ISCR2-virD2-floR-ISCR2-glmM-sul2 and IS26-aac(3)-IVa-aph(4)-Ia-ISEc59-tnpA-tet(X6)-orf-orf-ISCR2-glmM-sul2. Apart from tet(X6), P. cibarius HNCF44W harbored a novel transposon Tn6450b positive for blaNDM–1 on a conjugative plasmid. This study probed the genomic basis of three tet(X)-bearing, tigecycline-resistant strains, one of which coharbored blaNDM–1 and tet(X6), and identified P. cibarius as the important reservoir of tet(X6) variants. Emergence of P. cibarius encoding both blaNDM–1 and tet(X6) reveals a potential public health risk.
Highlights
Antimicrobial resistance (AMR) is a serious threat to public health globally
The antimicrobial susceptibility testing (AST) of tet(X)-positive tigecycline-resistant strains against 13 antibiotics was performed based on the broth microdilution method with Escherichia coli ATCC 25922 as the quality control and interpreted according to CLSI guidelines (CLSI, 2018)
Three tigecycline-resistant, tet(X)-positive Enterobacterales strains were isolated from 16 samples (18.8%), which consisted of Escherichia fergusonii HNCF11W carrying tet(X4), P. cibarius HNCF43W, and HNCF44W positive for a tet(X6) variant
Summary
Antimicrobial resistance (AMR) is a serious threat to public health globally. Carbapenem and tigecycline are regarded as vital antimicrobials reserved for clinical use due to their broad antibacterial spectrum. Plasmid-mediated resistance genes tet(X3) and tet(X4) conferring high-level resistance to tigecycline in Enterobacterales and Acinetobacter has been found to be ubiquitous in animals and food of animal origin (Bai et al, 2019; He et al, 2019; Sun et al, 2019; Li et al, 2020c). This undermines the efficacy of tigecycline as the last-resort drug in treating MDR bacterial infections, especially those caused by carbapenem-resistant, Gram-negative bacteria, such as CRE.
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