Spread of MCR-3 Colistin Resistance in China: An Epidemiological, Genomic and Mechanistic Study

Xu, Yongchang; Zhong, Lan-Lan; Srinivas, Swaminath; Sun, Jian; Huang, Man; Paterson, David L.; Lei, Sheng; Lin, Jingxia; Li, Xin; Tang, Zhenwei; Feng, Siyuan; Cong, Shan; Tian, Guo‐Bao; Feng, Youjun

doi:10.1016/j.ebiom.2018.07.027

Cited by 69 publications

(110 citation statements)

References 97 publications

(175 reference statements)

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“…Retrospectively, a similar scenario is seen with the MCR family of polymyxin resistance [12][13][14]. Not only have the new mcr variants already been extended from mcr-1 [1,14,15] to mcr-9 [16,17], but also some of them, like mcr-1 [1,12] and mcr-3 [1,18], have disseminated globally. Thus, it is in great demand to gain insights into the molecular epidemiology of tet(X)-mediated tigecycline resistance.…”

Section: Introductionmentioning

confidence: 74%

Harnessing efficient multiplex PCR methods to detect the expanding Tet(X) family of tigecycline resistance genes

Sun

et al. 2019

Virulence

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A growing number of tet(X)-type tigecycline resistance determinants [tet(X1) to tet(X5)] constitutes an expanding family of tetracycline-inactivating enzymes, posing a potential risk to global public health. Here, we report the development of an efficient multiplex PCR method to detect the family of tet(X) variants. This method is successfully applied in the screen and validation of tet(X) genes in the field and clinic bacterial samples. In addition, we found that the formerly proposed tet(X1) is a premature truncated version by the inappropriate annotation, and fixed this error. Overall, it might be the first genetic tool for the detection of different Tet(X) members.

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Section: Introductionmentioning

confidence: 74%

Harnessing efficient multiplex PCR methods to detect the expanding Tet(X) family of tigecycline resistance genes

Sun

et al. 2019

Virulence

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“…The mcr-4 has been identified first in S. enterica isolated from a pig on an 8,749 bp ColE10 plasmid in Italy [77,92]. Sequence analysis showed that mcr-4 has 34.0%, 35.0%, and 49.0% amino acid sequence identity to mcr-1, mcr-2, and mcr-3, respectively.…”

Section: Plasmid-mediated Resistance To Polymyxinsmentioning

confidence: 99%

“…Intriguingly, the determinants of transferable colistin resistance have extended further away mcr-1 to include a number of novel mcr-1 alleles [92]. Up to now, nine mcr alleles have been reported including mcr-1 [75][76][77][78][79]81,82,93], namely; mcr-2 (1617 bp) [79], mcr-3 (1626 bp) [82], mcr-4 (1626 bp) [77], mcr-5 (1644 bp) [76], mcr-6 (1617 bp) [75], mcr-7 (1620 bp) [81], mcr-8 (1698 bp) [78], and the most recently detected mcr-9 (2661 bp) [93] (Table 2).…”

Section: Plasmid-mediated Resistance To Polymyxinsmentioning

confidence: 99%

“…The analysis of the protein structure of MCR-1 showed the presence of two PEtN transferases, namely; LptA and EptC (or cptA) from Neisseria meningitidis and Campylobacter jejuni, respectively, both are intrinsically resistant to polymyxins [35,79]. Of note, mcr-2 and mcr-5 are viewed as two infrequent members of the MCR-like protein family [92].…”

Section: Plasmid-mediated Resistance To Polymyxinsmentioning

confidence: 99%

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Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

Ahmed

Zhong

Cong

et al. 2020

Emerging Microbes & Infections

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Increasing antibiotic resistance in multidrug-resistant (MDR) Gram-negative bacteria (MDR-GNB) presents significant health problems worldwide, since the vital available and effective antibiotics, including; broad-spectrum penicillins, fluoroquinolones, aminoglycosides, and β-lactams, such as; carbapenems, monobactam, and cephalosporins; often fail to fight MDR Gram-negative pathogens as well as the absence of new antibiotics that can defeat these "superbugs". All of these has prompted the reconsideration of old drugs such as polymyxins that were reckoned too toxic for clinical use. Only two polymyxins, polymyxin E (colistin) and polymyxin B, are currently commercially available. Colistin has re-emerged as a last-hope treatment in the mid-1990s against MDR Gram-negative pathogens due to the development of extensively drug-resistant GNB. Unfortunately, rapid global resistance towards colistin has emerged following its resurgence. Different mechanisms of colistin resistance have been characterized, including intrinsic, mutational, and transferable mechanisms. In this review, we intend to discuss the progress over the last two decades in understanding the alternative colistin mechanisms of action and different strategies used by bacteria to develop resistance against colistin, besides providing an update about what is previously recognized and what is novel concerning colistin resistance.

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“…Venezuela e 744 SSSI 4 (R) suggest that these genes are prone to mutations as they spread, as was observed in the isolates from Peru. A much higher prevalence of mcr-like genes from specific geographic locations (1,10,11) accompanied by the first report of mcr-1 in Pseudomonas aeruginosa (12) located on a chromosome demonstrate the ability of this gene to disseminate. Continued monitoring of mcr genes is warranted, but the development of global policies that might decrease the use of agents important to treat human infections or agents known to coselect for these resistance genes (13) seems prudent.…”

mentioning

confidence: 99%

Updated Prevalence of mcr -Like Genes among Escherichia coli and Klebsiella pneumoniae in the SENTRY Program and Characterization of mcr-1.11 Variant

Deshpande

Hubler

Davis

et al. 2019

Antimicrob Agents Chemother

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I ncreased prevalence of infections caused by Gram-negative pathogens that are multidrug resistant has prompted the reconsideration of polymyxins as therapeutic options. Resistance to polymyxins is due to mutations in the lipid A synthesis (1) that can be caused by the acquisition of mcr (2). Genes mcr-1 through mcr-8 (3, 4) and multiple subtypes have been reported to encode proteins that share 30 to 70% amino acid identity.We previously reported the prevalence of mcr-1 among Escherichia coli and Klebsiella pneumoniae isolates collected worldwide during 2014 and 2015 by the SENTRY Program (5). As an ongoing effort, colistin-resistant E. coli and K. pneumoniae clinical isolates collected in 2016 were screened for the presence of mcr, and a new mcr-1 variant was characterized.Among 11,493 E. coli and K. pneumoniae isolates tested, 199 (1.7%) were resistant to colistin per EUCAST criteria (6) and considered non-wild type by the CLSI (7) epidemiological cutoff value. Isolates displaying colistin MIC values of Ն4 mg/liter (resistant/ non-wild type) were screened for the mcr-1 and mcr-2 genes by PCR. All isolates carrying mcr were submitted to whole-genome sequencing.A total of 12 isolates were mcr-1 positive, including 10 E. coli isolates (2 in the United States, 3 [clonal] in Venezuela, 3 in Peru, 1 in Colombia, and 1 in Poland) and 2 K. pneumoniae isolates (1 each in Spain and Italy) (Table 1) recovered from invasive infections (Table 1). Colistin MIC values ranged from 4 to Ͼ8 mg/liter. No isolate yielded positive results for mcr-2.One E. coli isolate from Peru (sequence type 95 [ST95]) carried mcr-1 displaying an insertion of valine in amino acid position 6 and was designated mcr-1.11. This isolate showed susceptible phenotypes to ␤-lactams, aminoglycosides, tigecycline, and trimethoprim-sulfamethoxazole but resistance to tetracycline and quinolones ( Table 1). The mcr-1.11 gene was located on a 63-kb IncI2 plasmid carrying no other resistance genes (GenBank accession number KY853650). Two genetically unrelated E. coli isolates (ST7954 and ST1485) from the same hospital that carried mcr-1 displayed the same plasmid structure (Table 1; Fig. 1).The mcr-1.11 gene cloned in an E. coli background exhibited colistin and polymyxin B MIC results (2 to 8 mg/liter) similar to those of mcr-1 (2 to 4 mg/liter). The mcr-1.11 gene likely emerged via spontaneous mutation within a plasmid structure that is endemic to the medical center in Peru, as seems common among mcr-like genes (1).Unlike the vast majority of reports of mcr-like genes from animal-based sources, our results show a global prevalence of colistin resistance and mcr-1 among isolates collected from important human infections. Similar to the 2014 to 2015 survey, isolates carrying mcr-1 were identified in only 0.1% of the isolates tested; however, this study emphasizes its worldwide dissemination. Furthermore, our results and others (8,9) Citation Deshpande LM, Hubler C, Davis AP, Castanheira M. 2019. Updated prevalence of mcr-like genes among Escherichia coli and Kle...

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Spread of MCR-3 Colistin Resistance in China: An Epidemiological, Genomic and Mechanistic Study

Cited by 69 publications

References 97 publications

Harnessing efficient multiplex PCR methods to detect the expanding Tet(X) family of tigecycline resistance genes

Harnessing efficient multiplex PCR methods to detect the expanding Tet(X) family of tigecycline resistance genes

Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

Updated Prevalence of mcr -Like Genes among Escherichia coli and Klebsiella pneumoniae in the SENTRY Program and Characterization of mcr-1.11 Variant

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