Distribution and spread of the mobilised RND efflux pump gene cluster tmexCD-toprJ in clinical Gram-negative bacteria: a molecular epidemiological study

Dong, Ning; Zeng, Yu; Wang, Yao; Liu, Congcong; Lu, Jiayue; Cai, Chang; Li, Xue; Chen, Yongkui; Wu, Yantao; Fang, Yinfei; Fu, Yulin; Hu, Yanyan; Zhou, Hongwei; Cai, Jiachang; Hu, Fupin; Wang, Shaolin; Wang, Yan; Wu, Yongning; Chen, Gongxiang; Shen, Zhangqi; Chen, Sheng; Zhang, Rong

doi:10.1016/s2666-5247(22)00221-x

Cited by 46 publications

(27 citation statements)

References 21 publications

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“…Interestingly, variations of mexCD-oprJ genes have been found in mobile genetic elements in P. aeruginosa and several other bacteria [ 84 , 171 ]. A group of these mobile efflux pump operons have been called tmexCD-toprJ (“t” for transferable), and data suggest that they originated from the chromosome of a Pseudomonas spp.…”

Section: Efflux Pumps As a Mechanism Of Antimicrobial Resistance In ...mentioning

confidence: 99%

“…[ 85 ]. Several variations of the original tmexCD-toprJ have been identified since, either chromosomally or plasmid located, and have been directly associated with resistance to tetracyclines and reduced susceptibility to several other classes of antibiotics under laboratory conditions [ 84 , 85 ].…”

Section: Efflux Pumps As a Mechanism Of Antimicrobial Resistance In ...mentioning

confidence: 99%

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Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Lorusso

Carrara

Barroso

et al. 2022

IJMS

106

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Antimicrobial resistance is an old and silent pandemic. Resistant organisms emerge in parallel with new antibiotics, leading to a major global public health crisis over time. Antibiotic resistance may be due to different mechanisms and against different classes of drugs. These mechanisms are usually found in the same organism, giving rise to multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria. One resistance mechanism that is closely associated with the emergence of MDR and XDR bacteria is the efflux of drugs since the same pump can transport different classes of drugs. In Gram-negative bacteria, efflux pumps are present in two configurations: a transmembrane protein anchored in the inner membrane and a complex formed by three proteins. The tripartite complex has a transmembrane protein present in the inner membrane, a periplasmic protein, and a porin associated with the outer membrane. In Pseudomonas aeruginosa, one of the main pathogens associated with respiratory tract infections, four main sets of efflux pumps have been associated with antibiotic resistance: MexAB-OprM, MexXY, MexCD-OprJ, and MexEF-OprN. In this review, the function, structure, and regulation of these efflux pumps in P. aeruginosa and their actions as resistance mechanisms are discussed. Finally, a brief discussion on the potential of efflux pumps in P. aeruginosa as a target for new drugs is presented.

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Section: Efflux Pumps As a Mechanism Of Antimicrobial Resistance In ...mentioning

confidence: 99%

Section: Efflux Pumps As a Mechanism Of Antimicrobial Resistance In ...mentioning

confidence: 99%

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Lorusso

Carrara

Barroso

et al. 2022

IJMS

106

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“…Although there are different variants of the MDR efflux pumps tmexCD1-toprJ1, similar structures have also been found in Aeromonas caviae, Raoultella planticola, and Klebsiella quasipneumoniae, suggesting potential horizontal transfer mechanisms among various species (Wang et al, 2021a;Dong et al, 2022;Gao et al, 2022). The transfer of tnfxB2-tmexCD1-toprJ1 has previously been found to be mobilized by site-specific integrase (Lv et al, 2020).…”

Section: Discussionmentioning

confidence: 77%

Coexistence of tmexCD3-toprJ1b tigecycline resistance genes with two novel blaVIM-2-carrying and blaOXA-10-carrying transposons in a Pseudomononas asiatica plasmid

Qiao²,

Liang³

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionTigecycline and carbapenems are considered the last line of defense against microbial infections. The co-occurrence of resistance genes conferring resistance to both tigecycline and carbapenems in Pseudomononas asiatica was not investigated.MethodsP. asiatica A28 was isolated from hospital sewage. Antibiotic susceptibility testing showed resistance to carbapenem and tigecycline. WGS was performed to analyze the antimicrobial resistance genes and genetic characteristics. Plasmid transfer by conjugation was investigated. Plasmid fitness costs were evaluated in Pseudomonas aeruginosa transconjugants including a Galleria mellonella infection model.ResultsMeropenem and tigecycline resistant P. asiatica A28 carries a 199, 972 bp long plasmid PLA28.4 which harbors seven resistance genes. Sequence analysis showed that the 7113 bp transposon Tn7389 is made up of a class I integron without a 5’CS terminal and a complete tni module flanked by a pair of 25bp insertion repeats. Additionally, the Tn7493 transposon, 20.24 kp long, with a complete 38-bp Tn1403 IR and an incomplete 30-bp Tn1403 IR, is made up of partial skeleton of Tn1403, a class I integron harboring blaOXA-10, and a Tn5563a transposon. Moreover, one tnfxB3-tmexC3.2-tmexD3b-toprJ1b cluster was found in the plasmid and another one in the the chromosome. Furthermore, plasmid PLA28.4 could be conjugated to P. aeruginosa PAO1, with high fitness cost.DiscussionA multidrug-resistant plasmid carrying tmexCD3-toprJ1b and two novel transposons carrying blaVIM-2 and blaOXA-10 -resistant genes was found in hospital sewage, increasing the risk of transmission of antibiotic-resistant genes. These finding highlight the necessary of controlling the development and spread of medication resistance requires continuous monitoring and management of resistant microorganisms in hospital sewage.

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“…Strikingly, a kind of plasmid-located resistance-nodulation-division (RND) efflux pump, namely tmexCD1 - toprJ1 , that could confer resistance to tigecycline was identified in K. pneumoniae in 2020 in China ( Lv et al., 2020 ; Sun et al., 2020 ). To date, emergence of tmexCD1 - toprJ1 gene cluster and its variants are increasing in stock farming or nosocomial samples ( Wang et al., 2021a ; Wang et al., 2021b ; Gao et al., 2022 ), and the genetic structure characteristics of these plasmid-mediated tigecycline resistance determinants raised a major concern worldwide ( Dong et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Emergence of high-level colistin resistance mediated by multiple determinants, including mcr-1.1, mcr-8.2 and crrB mutations, combined with tigecycline resistance in an ST656 Klebsiella pneumoniae

Wang

Zhou

Liu

et al. 2023

Front. Cell. Infect. Microbiol.

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Colistin and tigecycline are usually regarded as the last resort for multidrug-resistant Klebsiella pneumoniae infection treatment. Emergence of colistin and tigecycline resistance poses a global healthcare challenge and is associated with high mortality due to limited therapeutic options. Here, we report the ST656 extensively drug-resistant K. pneumoniae strain KP15-652, which was isolated from a patient’s urine in China. Antimicrobial susceptibility testing showed it to be resistant to tigecycline, amikacin, levofloxacin, ciprofloxacin, and high-level colistin resistance (> 2048 mg/L). Whole-genome sequencing revealed that it harbors one chromosome and seven plasmids, including four plasmids carrying multiple acquired resistance genes. Transformation/conjugation tests and plasmid curing assays confirmed that mcr-1.1, mcr-8.2 and crrB mutations are responsible for the high-level colistin resistance and that a series of efflux pump genes, such as tmexCD1-toprJ1, tet(A) and tet(M), contribute to tigecycline resistance. mcr-1.1 and tet(M) are located on an IncX1 plasmid, which has conjugation transfer potential. mcr-8.2 and tet(A) are located on a multireplicon IncR/IncN plasmid but unable to be transferred via conjugation. Moreover, another conjugable and fusion plasmid carries the tmexCD1-toprJ1 gene cluster, which may have arisen due to IS26-mediated replicative transposition based on 8-bp target-site duplications. Importantly, a complex class 1 integron carrying various resistance genes was detected on this fusion plasmid. In conclusion, it is possible that the high-level of colistin resistance is caused by the accumulated effect of several factors on the chromosome and mcr-carrying plasmids, combined with many other resistances, including tigecycline. Effective surveillance should be performed to prevent further dissemination.

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Distribution and spread of the mobilised RND efflux pump gene cluster tmexCD-toprJ in clinical Gram-negative bacteria: a molecular epidemiological study

Cited by 46 publications

References 21 publications

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Coexistence of tmexCD3-toprJ1b tigecycline resistance genes with two novel blaVIM-2-carrying and blaOXA-10-carrying transposons in a Pseudomononas asiatica plasmid

Emergence of high-level colistin resistance mediated by multiple determinants, including mcr-1.1, mcr-8.2 and crrB mutations, combined with tigecycline resistance in an ST656 Klebsiella pneumoniae

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