Emergence of Carbapenem- and Tigecycline-Resistant Proteus cibarius of Animal Origin

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)-IVaaph(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 bla NDM−1 on a conjugative plasmid. This study probed the genomic basis of three tet(X)-bearing, tigecycline-resistant strains, one of which coharbored bla NDM−1 and tet(X6), and identified P. cibarius as the important reservoir of tet(X6) variants. Emergence of P. cibarius encoding both bla NDM−1 and tet(X6) reveals a potential public health risk.

Characterization of Fitness Cost Caused by Tigecycline-Resistance Gene tet(X6) in Different Host Bacteria

“…These data indicated that the increased expression of the tet(X6) gene will pose an extra burden on the bacteria growth of Enterobacteriaceae rather than the Proteus species. These results were consistent with previous findings that the overexpression of antibiotic resistance genes (ARGs) would inhibit the growth of certain bacteria and even lead to the death of bacteria [23,24]. We supposed that there are some regulation mechanisms or compensatory evolution that exist in P. mirabilis.…”

Comprehensive Genomic Investigation of Tigecycline Resistance Gene tet (X4)-Bearing Strains Expanding among Different Settings

“…However, He et al discovered the plasmid-mediated mobile tigecycline resistance genes tet (X3) and tet (X4) in Enterobacteriaceae and Acinetobacter in 2019, which posed a severe threat to global public health ( 8 ). Of concern, previous studies have shown that tet (X4) has been found to coexist with mcr-1 or bla NDM-1 in the same strain ( 9 , 10 ). The strains resistant to multiple last-resort antibiotics regarded as new superbugs may disseminate globally.…”

“…So far, tet (X4) has been discovered in several bacteria species such as Escherichia coli , Aeromonas caviae , Acinetobacter sp., and Escherichia fergusonii ( 8 , 10 – 12 ). Meanwhile, the tet (X4) gene is widely distributed on plasmids of diverse replicon types ( 13 ).…”

Genomic Characterization of a Proteus sp. Strain of Animal Origin Co-Carrying blaNDM-1 and lnu(G)

“…The bla NDM gene is largely carried on plasmids with a variety of replicon types [ 3 ], which play a vital role in the wide dissemination of bla NDM . In Proteus spp., bla NDM was either integrated into an SXT/R391 integrative and conjugative element [ 9 , 10 ] on bacterial chromosomes, or carried on plasmids with unknown replicon types, such as the recently reported pPrY2001-like plasmids [ 11 , 12 ]. In fact, the genetic characters of bla NDM -harboring plasmids in Proteus remain largely uncharacterized.…”