Abstract

The prevalence of tet(X) genes threatens the clinical use of last-line tigecycline. The tet(X6) gene has been reported in Proteus strains, but its genetic context is rarely reported. This study aimed to investigate the prevalence and genetic contexts of tet(X6) gene in Proteus spp. A tet(X6) variant-bearing P. terrae subsp. cibarius strain was subjected to susceptibility testing, determination of growth curves, scanning electron microscopy, transmission electron microscopy and whole-genome sequencing (WGS). The genomic contexts of the tet(X6)-positive strain were analysed by sequence comparison and annotation. ZJ19PC, a P. terrae subsp. cibarius strain harbouring the tet(X6) variant, was isolated from 20 cecum samples collected in Zhejiang, China. The chromosome size of ZJ19PC was 3 952 084 bp; the GC content was 38.2%; and hugA, sul2, tet(H), floR, dfra1, aadA1, aac(3)-IV and aph(4)-la were found in addition to the tet(X6) variant. Proteus spp. could be classified into three groups based on the tet(X6) gene contexts. Strain ZJ19PC belongs to group 1 (sra-sul2-ISCR2-floR-ISCR2-floR-ISCR2- tet(X6) variant-tnpA-ISEc59-aph(4)-la-aac(3)-Iva-IS26), and this region of group 1 was inserted between modA and guaA. The common antimicrobial resistance (AMR) genes of the three types of AMR gene islands were sul2, floR, tet(X6) and aac(3). The tet(X6) gene contexts and SNP tree showed that ZJ19PC was homologous to HNCF44W and HNCF43W, which indicated that these strains may be clonally transmitted. This study analysed the genetic contexts of the tet(X6) gene in Proteus spp. and highlighted the significance of monitoring tigecycline-resistant P. terrae subsp. cibarius.

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