应对可转移多黏菌素耐药性--饲料添加剂来源的白屈菜红碱具有双重效应

The emergence and spread of the mobile colistin-resistance gene,mcr-1,and its variants pose achallenge to the use of colistin,a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant(XDR)Gram-negative pathogens.Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens;however,few studies have considered the effects of adjuvants on limiting resistance-gene transmission.We found that chelerythrine(4 mg·L^(-1))derived from Macleaya cordata extract,which is used as an animal feed additive,reduced the minimal inhibitory concentration(MIC)of colistin against an mcr-1 positive Escherichia coli(E.coli)strain by 16-fold(from 2.000 to 0.125 mg·L^(-1)).eliminated approximately 10^(4) colony-forming units(CFUs)of an mcr-1-carrying strain in a murine intestinal infection model,and inhibited the conjugation of an mcr-1-bearing plasmid in vitro(by>100-fold)and in a mouse model(by up to 5-fold).A detailed analysis revealed that chelery-thrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity,thereby impairing respiration,disrupting proton motive force(PMF),generating reactive oxygen species(ROS),and decreasing intracellular adenosine triphosphate(ATP)levels,which subsequently downregu-lates mcr-1 and conjugation-associated genes.These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.

A One-Health Sampling Strategy to Explore the Dissemination and Relationship Between Colistin Resistance in Human,Animal,and Environmental Sectors in Laos

This study was designed to investigate the molecular epidemiology of mobile colistin resistance(mcr)using a"One-Health"approach in Laos and to predict whether any dominant plasmid backbone and/or strain type influences the dissemination of mcr.We collected 673 samples from humans(rectal normal flora),poultry,and the environment(water,flies,birds,etc.)in Vientiane,Lao People’s Democratic Republic(Laos),from May to September 2018.A total of 238 Escherichia coli(E.coli)isolated from nonduplicative samples,consisting of 98 MCR-positive E.coli(MCRPEC)("mcr"denotes the gene encoding mobile colistin resistance,and"MCR"denotes the subsequent protein encoded by mcr)and 140 MCRnegative E.coli(MCRNEC),were characterized by phenotype and Illumina sequencing.A subset of MCRPEC was selected for Min ION sequencing,conjugation assay,plasmid stability,and growth kinetics in vitro.The prevalence of MCRPEC was found to be 14.6%(98/673),with the highest prevalence in human rectal swabs(45.9%(45/98),p<0.0001,odds ratio(OR):0.125,95% confidence interval(CI):0.077-0.202).The percentages of MCRPEC from other samples were 14.3%(2/14)in dog feces,12.0%(24/200)in flies,11.0%(11/100)in chicken meat,8.9%(8/90)in chicken cloacal,8.0%(4/50)in chicken caeca,and 7.5%(4/53)in wastewater.MCRPEC was significantly more resistant to co-amoxiclav,sulfamethoxazoletrimethoprim,levofloxacin,ciprofloxacin,and gentamicin than MCRNEC(p<0.05).Genomic analysis revealed the distribution of MCRPEC among diverse clonal types.The putative plasmid Inc types associated with mcr-1 were Inc X4,Inc HI2,Inc P1,Inc I2,and Inc FIA,and those associated with mcr-3 were Inc FII,Inc FIA,Inc FIB,Inc P1,and Inc R.Recovery of highly similar plasmids from both flies and other sampling sectors implied the role of flies in the dissemination of mcr-1.mcr-positive plasmids were shown to be conjugative,and a significantly high transfer rate into a hypervirulent clone ST1193 was observed.Plasmids containing mcr irrespective of Inc type were highly stable and invariably did not exert a fitness effect upon introduction into a new host.These findings signify the urgent need for a standard infection control program to radically decontaminate the source of resistance.

Transmission of Carbapenem Resistance Between Human and Animal NDM-Positive Escherichia coli Strains

Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At present,the impact of livestock-associated CREC strains on human populations at the national level is unknown.Here,we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence.We also ascertain the blaNDMand blaKPCabundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin.Overall,631/29799(2.1%)clinical Escherichia coli(E.coli)isolates were identified as CREC.Multivariable analysis revealed that being male,an age below 1,an age between 13 and 18,provinces with greater chicken production,and provinces with higher pig production were associated with higher odds of CREC infection.In general,73.8%(n=45/61)of pig farms and 62.2%(n=28/45)of chicken farms had a blaNDMabundance of 1×10^(-5)to 1×10^(-3)and 1×10^(-3)to 1×10^(-2),respectively.Among all the Chinese NDM-positive E.coli(n=463)available at the National Center for Biotechnology Information(NCBI),the genomic analysis revealed that blaNDM-5and Inc X3 were the predominant carbapenemase gene-plasmid combination,while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels.All the findings suggest frequent CREC transmission between humans and animals,indicating that further discussions on the use of antibiotics in animals and humans are needed,both in China and across the globe.

Ending the Use of Human Antimicrobials in Food Production:The Good,the Bad,and the Ugly

Reducing the inappropriate use of antimicrobial drugs in food systems is a key priority for the Global Leaders Group on Antimicrobial Resistance(GLG)[1].Although access to high-quality antimicrobials is important for animal and plant welfare,global leaders recognize that preventing the existential threat of antimicrobial resistance(AMR)will not be possible without reducing the use of human antimicrobials used in food systems[1].

Advances in Antimicrobial Resistance

Antimicrobial resistance(AMR)is now considered to be another insidious pandemic and one that is becoming increasingly threatening.The global burden spawned by AMR has been widely reported and includes a large number of deaths and increased economic losses.Since the emergence of AMR can be driven by inappropriate antimicrobial use,and potential transmission of AMR has occurred between human and animals,many countries have tightened regulations on the use of antimicrobials in food systems.Yet there is still a long way to go,especially in low-and middleincome countries(LMICs),and new approaches are needed to further explore the emergence and spread of AMR in both human and animals.

Minimizing Risks of Antimicrobial Resistance Development in the Environment from a Public One Health Perspective

Antimicrobial resistance(AMR)is a globally recognized crisis with meaningful engagement across humans,animals,and the environment as in the One Health approach.The environment is the potential source,reservoir,and transmission route of AMR,and it plays a key role in AMR development from the One Health perspective.Animal farming,hospitals,and the pharmaceutical industry are identified as the main emission sources in the environment.Minimizing emissions and determining antimicrobial emission limits are priorities in the containment of environmental AMR development.From the perspectives of environmental management and environmental engineering,some important actions to minimize risks of AMR development are summarized,including the recent progress in enhanced hydrolysis pre-treatment technology to control the development of antibiotic resistance genes(ARGs)during biological wastewater treatment.It is desirable to establish a holistic framework to coordinate international actions on the containment of environmental AMR development.To establish a community with a shared future for humanity,China should and could play an important role in international cooperation to cope with AMR challenges.

Genomic Shift in Population Dynamics of mcr-1-positive Escherichia coli in Human Carriage

Emergence of the colistin resistance gene,mcr-1,has attracted worldwide attention.Despite the prevalence of mcr-1-positive Escherichia coli(MCRPEC)strains in human carriage showing a significant decrease between 2016 and 2019,genetic differences in MCRPEC strains remain largely unknown.We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019.We identified three major differences in MCRPEC strains between these two time points.First,the insertion sequence ISApl1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019.Second,the antibiotic resistance genes(ARGs),aac(3)-IVa and blaCTX-M-1,emerged and coexisted with mcr-1 in 2019.Third,MCRPEC strains in 2019 contained more virulence genes,resulting in an increased proportion of extraintestinal pathogenic E.coli(ExPEC)strains(36.1%)in MCRPEC strains in 2019 compared to that in 2016(10.5%),implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria.Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019,MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes,which may pose a potential public health threat.

World Antimicrobial Awareness Week 2021-Spread Awareness,Stop Resistance

The antimicrobial resistance(AMR)Tripartite organizations-the World Health Organization(WHO),the Food and Agriculture Organization of the United Nations(FAO),and the World Organization for Animal Health(Office International des Epizooties,OIE)-are pleased to announce that the theme of World Antimicrobial Awareness Week(WAAW)2021 will be“Spread Awareness,Stop Resistance”(1).China will participate in the WAAW 2021 and organize the China Antimicrobial Awareness Week(CAAW)2021.