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

Abstract

The emergence of plasmid-borne tet(X) genes mediates 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.

Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention

“…Ecological niches in which plasmid-encoded TIG resistance tet (X) genes have been detected are shown in Table 1 . Clearly, there is increasing evidence of plasmid-encoded TIG resistance tet (X) genes reported in countries across Europe, Asia, United States, South America, and Africa involving humans, food animals, including chickens, pigs, ducks, pigeons, geese, and cattle, as well as companion animals, food animal products (meats), aquaculture and environment such as soil, livestock-farm water, wastewaters, sewages, and wildlife as reservoirs of MTR ( Bai et al, 2019 ; Chen et al, 2019a , b , 2020 , 2021 ; He et al, 2019 ; Sun C. et al, 2019 , 2020 ; Sun J. et al, 2019 ; Cao et al, 2020 ; Cui et al, 2020 , 2021b ; Ding et al, 2020 ; Du et al, 2020 ; He T. et al, 2020 ; Li et al, 2020 , 2021f ; Ma et al, 2020 ; Pan et al, 2020 ; Ruan et al, 2020 ; Song et al, 2020 ; Wang et al, 2020a , b ; Zhang et al, 2020b , 2021 ; Zheng et al, 2020 ; Cheng et al, 2021a , b ; Feng et al, 2021 ; Hirabayashi et al, 2021a , b ; Hsieh et al, 2021 ; Li et al, 2021e , f ; Lu et al, 2021 ; Marathe et al, 2021 ; Martelli et al, 2021 ; Mohsin et al, 2021 ; Soliman et al, 2021 ; Sun et al, 2021a , b ; Tang et al, 2021 ; Wang et al, 2021f , g ; Xu et al, 2021 ; Yu Y. et al, 2021 ; Wu et al, 2022 ; Zhai et al, 2022 ). We further demonstrate this, through the specific reservoirs in which plasmid-borne transmissible tet (X) and tmexCD-toprJ genes have been detected as shown in Table 2 .…”

“…Publications involving tet (X) genes appear to be more in humans, chickens and pigs, whereas those for tmexCD-toprJ genes appear to be more in humans and chickens. It is important to reiterate that from these ecological niches, the various MTR genes, such as tet (X3/3.2), tet (X4), tet (X5/5.2/5.3), tet (X6), tet (X7), and tet (X18), have been detected in a diversity of bacteria, which include Escherichia , Rauoltella , Myroides , Enterobacter , Citrobacter , Klelbsiella , Shingobacterium multivorum , Proteus , Acinetobacter , Salmonella , Riemerella anatipestifer , and Empedobacter brevis ( Bai et al, 2019 ; He et al, 2019 ; Sun C. et al, 2019 ; Yongchang et al, 2019 ; Li et al, 2020 , 2021a , c , d , 2022 ; Liu et al, 2020 ; Wang et al, 2020a , 2021f ; Zhang et al, 2020a , b ; Chen et al, 2021 ; Cheng et al, 2021a , b ; Soliman et al, 2021 ; Xu et al, 2021 ). Notably, sequence alignment results revealed that tet (X5.2/5.3) genes shared 96.3–100% nucleotide sequence identity with tet (X6) and its variant ( Chen et al, 2020 ; He D. et al, 2020 ; Zheng et al, 2020 ).…”

“…TIG use-selection pressure can induce the expression of tet (X) in ICE leading to excision and production of the conserved conjugation machinery (a T4SS), thereby possibly promoting genetic transfer to recipients ( Zhang et al, 2020a ). Moreover, MTR gene-bearing [especially tet (X)-bearing] plasmids are stably maintained and increase the growth rate of recipient organism ( Cheng et al, 2021b ), thus posing a challenge to antimicrobial therapy.…”