Within-host heterogeneity and flexibility of mcr-1 transmission in chicken gut

Li, Xingping; Sun, Ruan-Yang; Song, Jiaqi; Fang, Liang‐Xing; Zhang, Rong-Min; Lian, Xinlei; Liao, Xiao‐Ping; Liu, Yahong; Lin, Jun; Sun, Jian

doi:10.1016/j.ijantimicag.2019.09.010

Cited by 35 publications

(25 citation statements)

References 42 publications

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“…Lastly, mcr-1 was located on IncI plasmids p40EC-4 and p94EC-3 of 40EC and 94EC, respectively, and have lost both upstream and downstream IS Apl1 . p40EC-4 and p94EC-3 share a similarity of 99.68% and are highly similar to other mcr-1 carrying IncI plasmids reported in previous studies 18, 21 . The loss of IS Apl1 by mcr-1 was suggested to contribute to the stability of the plasmid replicon, causing the mobilization of mcr-1 solely to rely on the conjugative transfer of the plasmid 22 .…”

Section: Resultssupporting

confidence: 82%

See 1 more Smart Citation

Whole-genome analysis of antimicrobial-resistantEscherichia coliin human gut microbiota reveals its origin and flexibility in transmittingmcr-1

Ding

Saw

Tan

et al. 2021

Preprint

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Multidrug resistant (MDR) Escherichia coli strains that carry extended-spectrum β-lactamases (ESBLs) or colistin resistance gene mcr-1 have been identified in the human gut at an increasing incidence worldwide. In this study, we sampled and characterized MDR Enterobacteriaceae from the gut microbiota of healthy Singaporeans and show that the prevalence of ESBL-producing and mcr-positive Enterobacteriaceae is 26.6% and 7.3%, respectively. Whole-genome sequencing of 37 E. coli isolates identified 25 sequence types and assigned them into six different phylogroups, suggesting that the human intestinal MDR E. coli strains are highly diverse. In addition, we found that E. coli isolates belonging to phylogroup D, B2 and F carry a higher number of virulence genes, whereas isolates of phylogroup A, B1 and E carry fewer virulence factor genes but are frequent carriers of florfenicol resistance gene floR and colistin resistance gene mcr-1. Comparison of the seven mcr-1-positive E. coli isolates revealed that mcr-1 is carried by conjugative plasmids or embedded in composite transposons, which could potentially mobilize mcr-1 to other pathogenic Enterobacteriaceae strains or MDR plasmids. Finally, we found that 12 out of the 37 MDR E. coli isolates in this study show high similarity to ESBL-producing E. coli isolates from raw meats from local markets, suggesting a potential transmission of MDR E. coli from meat products to the human gut microbiota. Our findings show diverse antibiotic resistance and virulence profiles of intestinal E. coli and call for better countermeasures to block the transmission of MDR E. coli via the food chain. Importance: The human gut can harbor both antibiotic resistant and virulent E. coli which may subsequently cause infections. In this study, the antibiotic resistance and virulence traits of antibiotic-resistant E. coli isolates from human gut microbiota of healthy subjects were investigated. The isolated E. coli strains carry a diverse range of antibiotic resistance mechanisms and virulence factor genes, are highly diverse to each other, and are likely to originate from raw meat products from the local markets. Of particular concern are seven E. coli isolates which carry colistin resistance gene mcr-1. This gene can be mobilized into other pathogens and MDR plasmids, thereby spreading resistance to the last-resort antibiotic colistin. Our findings also suggest that raw meat could serve as important source to transmit MDR bacteria into the human gut microbiota.

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Section: Resultssupporting

confidence: 82%

“…Therefore, surveillance of local mcr-1 dissemination should be conducted. In addition, the two IncI plasmids p40EC-4 and p94EC-3 are highly similar to IncI type mcr-1 -carrying plasmids reported previously in China 18, 21 , suggesting a potential direct epidemiological linkage.…”

Section: Discussionsupporting

confidence: 77%

Whole-genome analysis of antimicrobial-resistantEscherichia coliin human gut microbiota reveals its origin and flexibility in transmittingmcr-1

Ding

Saw

Tan

et al. 2021

Preprint

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“…strain ZZW20, Salmonella sp. strain 15E464, E. coli mh1655, and E. coli ATCC 700603 were provided by Jian Sun (38), South China Agricultural University. The other mcr-1positive or mcr-1-negative E. coli and Klebsiella pneumoniae isolates originated from our previous studies (20,39).…”

Section: Methodsmentioning

confidence: 99%

Honokiol Restores Polymyxin Susceptibility to MCR-1-Positive Pathogens both In Vitro and In Vivo

Guo

Wang³

et al. 2020

Appl Environ Microbiol

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The emergence of the plasmid-mediated colistin resistance gene mcr-1 has led to serious multidrug-resistant (MDR) Enterobacteriaceae infections, which are a great threat to the clinic. This study aims to find an inhibitor of MCR-1 to reestablish the use of polymyxins against MDR Enterobacteriaceae infections. Here, we determined that the natural compound honokiol could enhance the efficacy of polymyxins against MDR Enterobacteriaceae infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, Western blotting, molecular simulation dynamics, and mouse infection models. The MIC results indicated that honokiol can recover the sensitivity of polymyxins against MCR-1-positive Klebsiella pneumoniae and Escherichia coli (with a fractional inhibitory concentration index ranging from 0.09 ± 0.00 to 0.27 ± 0.06). Based on time-kill curve analysis, all of the tested bacteria were killed within 1 h following the combined therapy with honokiol and polymyxins. Molecular simulation dynamics results suggested that honokiol directly binds to the MCR-1 active region, reducing the biological activity of MCR-1. The combination of honokiol and polymyxins could increase the 40% protection rate and reduce the bacterial load on the thigh muscles of mice. Our study indicates that honokiol is a predominant natural compound whose combination therapy with polymyxins is very promising in future treatment options for MCR-1-positive Enterobacteriaceae infections. IMPORTANCE In the present study, honokiol could effectively inhibit the activity of MCR-1 and showed almost no cytotoxicity to MH-S cells. According to our results, the combination of honokiol and polymyxin had a clear synergistic effect against MCR-1-positive Enterobacteriaceae in vitro. Combination therapy also showed a powerful therapeutic effect in vivo, which can significantly improve mouse livability, reduced the load of bacteria, and reduced pathological change. This combined therapy of small molecule compounds and antibiotics may not continue to induce new bacterial resistance, due to the fact that MCR-1 targeted by honokiol is not indispensable for the bacterial viability; on the other hand, it can reduce the dosage of combined antibiotics, and it is also a promising alternative therapy for the treatment of drug-resistant infections in the future.

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“…21,22 Besides, MDR ESBL-, MCR-1-, and MCR-8.2-producing K. quasipneumoniae have been described in animals (e.g., dog, chicken, pig, and turtle) from China, Japan, and Taiwan. [23][24][25][26] In Brazil, an isolate of KPC-2-and OKP-B-6-producing K. quasipneumoniae subsp. similipneumoniae was reported in nosocomial infection 27 and the co-occurrence of CTX-M-15 and KPC-9 in a clinical strain of MDR K. quasipneumoniae subsp.…”

Section: Resultsmentioning

confidence: 99%

Genomic Characterization of a Multidrug-Resistant and Hypermucoviscous/Hypervirulent Klebsiella quasipneumoniae subsp. similipneumoniae ST4417 Isolated from a Sewage Treatment Plant

Furlan

Gallo

Campos

et al. 2020

Microbial Drug Resistance

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Clinical strains of Klebsiella quasipneumoniae subsp. similipneumoniae have been reported worldwide. Multidrug-resistant (MDR) hypermucoviscous (hm)/hypervirulent (hv) lineages have become a global problem for public health worldwide. Therefore, this study aimed to characterize by whole-genome sequencing a MDRhm/hv K. quasipneumoniae subsp. similipneumoniae SWT10 strain belonging to the new sequence type ST4417 isolated from a sewage treatment plant. Results: The SWT10 strain was recovered from a sewage treatment plant in Brazil and presented the hm and MDR phenotypes. Resistome analysis showed antimicrobial resistance genes associated with resistance to fluoroquinolones, b-lactams, tetracyclines, trimethoprim, aminoglycosides, sulfonamides, macrolides, and fosfomycin as well as several heavy metal resistance genes. Virulome analysis showed virulence factors related to hv lineages. Multilocus sequence typing analysis revealed the new ST4417, which was grouped in CC1584 by the minimum-spanning tree. Besides, five plasmid incompatibility groups, two prophage-related sequences, and 66 genomic islands were detected. Conclusion: This study reports for the first time the genome sequence of a MDR-hm/hv K. quasipneumoniae subsp. similipneumoniae recovered from the environment, which contributes to a better understanding about these lineages as well as for surveillance studies worldwide.

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Within-host heterogeneity and flexibility of mcr-1 transmission in chicken gut

Cited by 35 publications

References 42 publications

Whole-genome analysis of antimicrobial-resistantEscherichia coliin human gut microbiota reveals its origin and flexibility in transmittingmcr-1

Whole-genome analysis of antimicrobial-resistantEscherichia coliin human gut microbiota reveals its origin and flexibility in transmittingmcr-1

Honokiol Restores Polymyxin Susceptibility to MCR-1-Positive Pathogens both In Vitro and In Vivo

Genomic Characterization of a Multidrug-Resistant and Hypermucoviscous/Hypervirulent Klebsiella quasipneumoniae subsp. similipneumoniae ST4417 Isolated from a Sewage Treatment Plant

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