Abstract
Tigecycline is the antibiotic of last resort for the treatment of extensively drug-resistant bacterial infections, mainly those of multidrug-resistant Gram-negative bacteria. The plasmid-mediated tet(X3) gene has recently been described in various pathogens that are resistant to tigecycline. We report three tigecycline-resistant Acinetobacter towneri strains isolated from porcine faeces in China, which all contained the tet(X3)-harboring plasmids. A broth microdilution method was used to examine the antimicrobial susceptibility of the isolates, and S1-Nuclease digestion pulsed-field gel electrophoresis (S1-PFGE) was used to characterize their plasmid profiles. The whole-genome sequences of the isolates were determined with the Nanopore PromethION platform. The sequence analysis indicated that the strains were A. towneri. They showed resistance to multiple antibiotics, and all the resistance genes were located on plasmids. The three tet(X3)-harboring plasmids had a similar backbone structure, and all contained bla OXA-58 with various insertion elements (IS). ISCR2 is considered an important factor in tet(X3) mobilization. In addition to ISCR2, we demonstrate that IS26 generates a circular intermediate containing the tet(X3) gene, which could increase the dissemination risk. To our knowledge, this is the first report of tet(X3)- and bla OXA-58-harboring plasmids in A. towneri. Because the IS26 is frequently found in front of tet(X3), research should be directed toward the action of IS26 in the spread of tet(X3).
Highlights
Tigecycline, a broad-spectrum modified minocycline derivative, is considered a drug of last resort against multidrug-resistant (MDR) bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE) (Tasina et al, 2011)
The rpoB gene was used to identify the Acinetobacter isolates at the species level. This analysis showed that strain GX3 was identical to GX5, and when compared with Acinetobacter spp. from the GenBank database, it shared a high degree of nucleotide similarity (99.85%) with strain 19110F47 isolated from the faeces of swine in China (CP046045.1)
A structural analysis of the three tet(X3)harboring plasmids showed that they shared a high degree of nucleotide similarity (≥91%), suggesting that they may be derived from the same ancestral MDR plasmid backbone (Figure 1A)
Summary
Tigecycline, a broad-spectrum modified minocycline derivative, is considered a drug of last resort against multidrug-resistant (MDR) bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE) (Tasina et al, 2011). The tet(X3) gene has been identified in Acinetobacter baumannii, A. schindleri, A. indicus, and Empedobacter brevis, but limited information about the mechanisms of tet(X3) transmission in bacteria is available (Li et al, 2019; He et al, 2020a). It has been shown that tet(X3) is transferred by plasmids or transposons in a mechanism called ‘rolling-circle (RC) transposition’ via ISCR2 (He et al, 2019). Plasmids carrying both tet(X3) and blaNDM-1 were detected in A. indicus in a recent study, but with no information on the plasmid containing tet(X3) together with other carbapenemase genes in A. towneri (He et al, 2020a)
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