Journal ArticleDOI
Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study
Yiyun Liu,Yang Wang,Timothy R. Walsh,Ling-Xian Yi,Rong Zhang,James Spencer,Yohei Doi,Guo-Bao Tian,Baolei Dong,Xianhui Huang,Lin-Feng Yu,Danxia Gu,Hongwei Ren,Xiaojie Chen,Luchao Lv,Dandan He,Hongwei Zhou,Zi-sen Liang,Jian-Hua Liu,Jianzhong Shen +19 more
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TLDR
The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance, in Enterobacteriaceae and emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.Abstract:
Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10 −1 to 10 −3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.read more
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Natural Products as Sources of New Drugs from 1981 to 2014
David J. Newman,Gordon M. Cragg +1 more
TL;DR: This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012, and the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide.
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Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019.
David J. Newman,Gordon M. Cragg +1 more
TL;DR: Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, they are still able to identify only two de novo combinatorials compounds approved as drugs in this 39-year time frame.
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The antimicrobial activity of nanoparticles: present situation and prospects for the future
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Global increase and geographic convergence in antibiotic consumption between 2000 and 2015.
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TL;DR: It is found that the antibiotic consumption rate in low- and middle- income countries (LMICs) has been converging to (and in some countries surpassing) levels typically observed in high-income countries, and projected total global antibiotic consumption through 2030 was up to 200% higher than the 42 billion DDDs estimated in 2015.
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Antibiotic resistance: a rundown of a global crisis.
Bilal Aslam,Wei Wang,Muhammad Imran Arshad,Mohsin Khurshid,Saima Muzammil,Muhammad Hidayat Rasool,Muhammad Atif Nisar,Ruman Farooq Alvi,Muhammad Aamir Aslam,Muhammad Usman Qamar,Muhammad Khalid Farooq Salamat,Zulqarnain Baloch +11 more
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References
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TL;DR: A new membrane protein topology prediction method, TMHMM, based on a hidden Markov model is described and validated, and it is discovered that proteins with N(in)-C(in) topologies are strongly preferred in all examined organisms, except Caenorhabditis elegans, where the large number of 7TM receptors increases the counts for N(out)-C-in topologies.
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Journal ArticleDOI
Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study
Karthikeyan Kumarasamy,Mark Toleman,Timothy R. Walsh,Jay Bagaria,Fafhana Butt,Ravikumar Balakrishnan,Uma Chaudhary,Michel Doumith,Christian G. Giske,Seema Irfan,Padma Krishnan,Anil Kumar,Sunil Maharjan,Shazad Mushtaq,Tabassum Noorie,David L. Paterson,A. Pearson,Claire Perry,Rachel Pike,Bhargavi Rao,Ujjwayini Ray,Jayanta B. Sarma,Madhu Sharma,Elizabeth Sheridan,M A Thirunarayan,Jane F. Turton,Supriya Upadhyay,Marina Warner,William Welfare,David M. Livermore,Neil Woodford +30 more
TL;DR: The prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK is investigated, and co-ordinated international surveillance is needed.