Presence of Mobile Tigecycline Resistance Gene tet (X4) in Clinical Klebsiella pneumoniae

Abstract

Tigecycline, the first member of glycylcycline class antibiotic, is often considered one of the effective antibiotics against multidrug-resistant (MDR) infections. However, the emergence and wide distribution of two novel plasmid-mediated tigecycline resistance genes, tet (X3) and tet (X4), pose a great threat to the clinical use of tigecycline.

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 .…”

“…This situation would suggest that the plasmid homologous recombination may occur in the recipient organisms following the acquisition of mobile tet (X). The homologous plasmid recombination (of IS 26 ) has been speculated to involve the horizontal transfer (conjugation) of tet (X4) borne on a small non-self-transmissible plasmid possessing T4SS, whereby the small plasmid incorporated into bigger and broader-host plasmids that enabled tet (X4) transmission to recipient organism ( Zhai et al, 2022 ). Notably, the tet (X4)-IncF family plasmids appear commonly observed in the form of hybrid plasmid ( Du et al, 2020 ; Li et al, 2020 ; Sun C. et al, 2020 ; Zhang et al, 2020a ; Zhai et al, 2022 ).…”

“…The homologous plasmid recombination (of IS 26 ) has been speculated to involve the horizontal transfer (conjugation) of tet (X4) borne on a small non-self-transmissible plasmid possessing T4SS, whereby the small plasmid incorporated into bigger and broader-host plasmids that enabled tet (X4) transmission to recipient organism ( Zhai et al, 2022 ). Notably, the tet (X4)-IncF family plasmids appear commonly observed in the form of hybrid plasmid ( Du et al, 2020 ; Li et al, 2020 ; Sun C. et al, 2020 ; Zhang et al, 2020a ; Zhai et al, 2022 ). This understanding may explain why tet (X4)—a gene proven to possess a high HGT frequency ( Li et al, 2021c ), appears to breach the biological boundaries and able to spread onto different bacterial genus and species.…”

Tigecycline-resistant Escherichia coli ST761 carrying tet(X4) in a pig farm, China

“…It has sporadically reported in countries outside of China, e.g., Singapore, Pakistan, Vietnam, United Kingdom, and Norway ( Ding et al, 2020 ; Marathe et al, 2021 ; Mohsin et al, 2021 ; Dao et al, 2022 ; Martelli et al, 2022 ). The tet (X4) has subsequently detected in various Enterobacteriaceae species, such as Proteus , A. baumannii , Aeromonas caviae , Citrobacter freundii , Enterobacter cloacae , E. hormaechei , Klebsiella pneumoniae , and Shewanella xiamenensis ( Chen et al, 2019 ; He et al, 2019 ; Zeng et al, 2021 ; Dao et al, 2022 ; Li et al, 2022 ; Wu et al, 2022 ; Zhai et al, 2022 ).…”

Fecal Carriage of Escherichia coli Harboring the tet(X4)-IncX1 Plasmid from a Tertiary Class-A Hospital in Beijing, China

“…The tet (X4) gene was predominantly found in pigs, pork, and the surrounding environments of pig farms or slaughterhouses but was rare in human health sectors. Unfortunately, the presence of tet (X4) progressively increased in clinical cases [ 18 , 19 ] and in healthy humans [ 15 ]. Moreover, a greater concern is that the tet (X4) gene has been sporadically found in coexistence with the mobile colistin gene, mcr-1, [ 20 ] or carbapenemase-encoding gene bla NDM-5 [ 21 ], further limiting the drug options for the treatment of infections caused by these extensively drug-resistant bacterial pathogens.…”