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bioRxiv · 10.1101/2021.08.02.454847

Global dissemination of tet(X3) and tet(X6) among livestock-associated Acinetobacter is sporadically mediated by highly diverse plasmidomes

Zhou, K.·Cheng, Y.·Liu, Y.·Chen, Y.·Huang, F.·Chen, R.·Xiao, Y.
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Abstract

The emergence of plasmid-borne tet(X) genes mediated high-level resistance of tigecycline largely threatening its clinical effectiveness. Currently, the dissemination pattern of plasmid-borne tet(X) genes remains unclear. In this study, 684 fecal and environmental samples were collected at six livestock farms, and 15 tet(X)-positive Acinetobacter isolates were recovered, mainly including 9 tet(X3)- and 5 tet(X6)-positive A. towneri strains. A clonal dissemination of tet(X3)-positive A. towneri was detected in a swine farm, while the tet(X6)-positive A. towneri strains mainly sporadically disseminated in the same farm. A tet(X3)-carrying plasmid (pAT181) was self-transmissible from a tigecycline-susceptible A. towneri strain to A. baumannii ATCC17978, causing a 128-fold and 64-512-fold increase in the MIC values of tigecycline and the other tetracyclines, respectively. Worrisomely, pAT181 was stably maintained and increased the growth rate of ATCC17978. Further identification of tet(X)s in 10,680 Acinetobacter genomes retrieved from GenBank revealed that, tet(X3) (n=249) followed by tet(X5)-like (n=61) and tet(X6) (n=53) are the prevalent alleles mainly carried by four species, and most of them are livestock associated. Phylogenetic analysis showed that most of tet(X3)- and tet(X6)-positive isolates disseminate sporadically. The structures of tet(X3) and tet(X6) plasmidomes are highly diverse and no epidemic plasmids have emerged yet. However, cross-species and cross-region transmissions of tet(X3) might have been mediated by several plasmids in a small proportion of strains. Our study evidence that tet(X3) and tet(X6) currently disseminate sporadically in Acinetobacter. Continuous surveillance for tet(X)s in the context of One Health is necessary to prevent them from transmitting to humans. ImportanceRecently identified plasmid-borne tet(X) genes highly challenged the efficiency of tigecycline, a last resort antibiotic for severe infection. Currently, the dissemination pattern of plasmid-borne tet(X) genes remains unclear. In this study, we first identified plasmid-borne tet(X)-positive Acinetobacter spp. strains from fecal and environmental samples collected at six livestock farms. A clonal dissemination of tet(X3)-positive A. towneri was detected in a swine farm, while the tet(X6)-positive A. towneri strains mainly disseminated sporadically in the same farm. A tet(X3)-carrying plasmid was found self-transmissible resulting in enhanced tigecycline resistance and growth rate. Further exploring a global dataset of tet(X)-positive Acinetobacter genomes retried from GenBank revealed that most of tet(X3) and tet(X6)-positive isolates share highly distant relationship, and the structures of tet(X3) and tet(X6) plasmidomes are highly diverse. Our study evidence that tet(X3) and tet(X6) disseminate sporadically in Acinetobacter and continuous surveillance for tet(X)s in the context of One Health is necessary.

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Zhou, K., Cheng, Y., Liu, Y., Chen, Y., Huang, F., Chen, R., Xiao, Y.. 2021-08-03. Global dissemination of tet(X3) and tet(X6) among livestock-associated Acinetobacter is sporadically mediated by highly diverse plasmidomes. https://doi.org/10.1101/2021.08.02.454847

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