An ecological approach to assessing the epidemiology of antimicrobial resistance in animal and human populations

We examined long-term surveillance data on antimicrobial resistance (AMR) in Salmonella Typhimurium DT104 (DT104) isolates from concurrently sampled and sympatric human and animal populations in Scotland. Using novel ecological and epidemiological approaches to examine diversity, and phenotypic and temporal relatedness of the resistance profiles, we assessed the more probable source of resistance of these two populations. The ecological diversity of AMR phenotypes was significantly greater in human isolates than in animal isolates, at the resolution of both sample and population. Of 5200 isolates, there were 65 resistance phenotypes, 13 unique to animals, 30 unique to humans and 22 were common to both. Of these 22, 11 were identified first in the human isolates, whereas only five were identified first in the animal isolates. We conclude that, while ecologically connected, animals and humans have distinguishable DT104 communities, differing in prevalence, linkage and diversity. Furthermore, we infer that the sympatric animal population is unlikely to be the major source of resistance diversity for humans. This suggests that current policy emphasis on restricting antimicrobial use in domestic animals may be overly simplistic. While these conclusions pertain to DT104 in Scotland, this approach could be applied to AMR in other bacteria-host ecosystems.     

Addressing antimicrobial resistance by improving access and quality of care—A review of the literature from East Africa

Universal access to healthcare, including quality medicines, is a fundamental human right but is still out of reach for many in low- and middle-income countries (LMICs). An existing framework capturing variability of access to healthcare in low-resource settings includes the 5 dimensions: availability, accessibility, affordability, adequacy, and acceptability. This framework encompasses key components, including health infrastructure and means to access it as well as service organisation, costs, and factors that influence users’ satisfaction. However, in reality, the effectiveness of accessed healthcare is measured by the likelihood of a positive outcome. We therefore propose an expansion of this framework to include an additional dimension, “aspects of quality,” incorporating quality, which critically influences the ability of the accessed services to generate optimal health outcomes. Within this framework, we explore literature from East Africa likely relevant to a range of LMIC contexts, mainly focusing on the provision of widely used antimicrobials such as antimalarials and antibiotics. We argue that major inadequacies exist across all 6 dimensions of access and quality of drugs and their provision. While the global focus is on curbing excessive antimicrobial use to tackle the antimicrobial resistance (AMR) crisis, major constraints around access shape patients’ health-seeking decisions leading to potentially problematic practices that might exacerbate the AMR problem. We advocate for a holistic approach to tackling these inadequacies, encompassing all dimensions of access and quality of healthcare in order to improve health outcomes while simultaneously counteracting the AMR crisis.     

耐药微生物和抗生素耐药基因与全健康

因人类的各种活动,耐药微生物和抗生素耐药基因在“人-动物-环境”界面发生跨物种和跨生境的传播。将人类、动物和环境视作有机整体的“全健康”（One Health）理念有望成为解决这种传播的有效策略。抗生素及其代谢活性产物在环境中富集,再经动物及动物制品传播到人,产生耐药微生物并造成耐药基因的传播。本文综述了人-动物-环境界面耐药菌和抗生素耐药基因传播的流动与循环,总结了我国和其他国家应对抗生素耐药性问题的政策,倡导更多的国家和地区将“全健康”理念和方法用于控制抗生素耐药性传播;通过医疗卫生部门、食品药品监督管理部门、农林渔牧部门与教育、财政等多部门合作来应对抗生素耐药性的全球挑战。     

Healing across Cultures: Learning from Traditions

The health and wellness of an individual are reliant on the integrated effects of mind, body, and spirit. This triad is intricately set within a backdrop of the environment, our earth. Western cultures often disregard this holism, especially this fourth component, in its considerations of wellness as described by modern medicine. This practice is unlike that of many of the traditional cultures in the world. These cultures focus more on balance in the context of environmental respect. Varied cultures share remarkable similarities in their healing modalities, especially considering the relative isolation from one to another—evidence that there is truth to the healing knowledge they possess. We are not disconnected from the natural world in terms of health, but dependent and interconnected within ourselves and to everything around us. Social change is required to assure that the practice of modern medicine evolves to incorporate this integral aspect of health and wellness, and this can be done through partnerships with traditional healers.There is a growing demand for wellness and earthly responsibility. It is time to appropriately learn from age-old societies and their healing traditions for they do have answers we are seeking in sustainability and harmony, environmental stewardship and planetary respect, and holistic health. For thousands of years, our ancestors have known the secrets of long life—this knowledge needs to be preserved through the apprenticeship of future generations. We propose a collaboration that develops mutually beneficial learning partnerships combining modern medical knowledge with the wisdom of traditional healers around the world.     

Genetic capitalism and stabilizing selection of antimicrobial resistance genotypes in Escherichia coli

Antimicrobial resistance (AMR) in pathogenic strains of bacteria, such as Escherichia coli (E. coli), adversely impacts personal and public health. In this study, we examine competing hypotheses for the evolution of AMR including (i) ‘genetic capitalism’ in which genotypes that confer antibiotic resistance are gained and not often lost in lineages, and (ii) ‘stabilizing selection’ in which genotypes that confer antibiotic resistance are gained and lost often. To test these hypotheses, we assembled a dataset that includes annotations for 409 AMR genotypes and a phylogenetic tree based on genome-wide single nucleotide polymorphisms from 29 255 isolates of E. coli collected over the past 134 years. We used phylogenetic methods to count the times each AMR genotype was gained and lost across the tree and used model-based clustering of the genotypes with respect to their gain and loss rates. We demonstrate that many genotypes cluster to support the hypothesis for genetic capitalism while a few genotypes cluster to support the hypothesis for stabilizing selection. Comparing the sets of genotypes that fall under each of the hypotheses, we found a statistically significant difference in the breakdown of resistance mechanisms through which the AMR genotypes function. The result that many AMR genotypes cluster under genetic capitalism reflects that strong positive selective forces, primarily induced by human industrialization of antibiotics, outweigh the potential fitness costs to the bacterial lineages for carrying the AMR genotypes. We expect genetic capitalism to further drive bacterial lineages to resist antibiotics. We find that antibiotics that function via replacement and efflux tend to behave under stabilizing selection and thus may be valuable in an antibiotic cycling strategy.     

Improving the dialogue between public health and ecosystem science on antimicrobial resistance

The concept of health has evolved markedly from a bio-medical, mechanistic model to include an interdisciplinary perspective where human, animal and ecosystem health are integrated. One Health, EcoHealth and Planetary Health are examples of approaches to health advocating collaboration and interdisciplinarity at multiple levels. In practice, successful integration has been challenging and in particular, understanding of the ecosystem component of health lags behind the human and animal components. Antimicrobial resistance is an important threat to human health, which develops, is maintained and transmitted at the human–animal–environment interface. While the human and livestock components of resistance are well understood, this is not the case for the ecosystem component. This gap in knowledge leads to a poor representation of the environmental dimension of antimicrobial resistance in key policy documents and in interdisciplinary work around this issue. We interviewed a group of leading researchers in public health and ecology to explore their perceptions on the integration of ecosystem and public health research in the context of antimicrobial resistance. Experts from both fields considered that research on antimicrobial resistance is only beginning to consider ecosystems. They highlighted various barriers that have contributed to limited integration, such as conceptual barriers, and a lack of knowledge translators as facilitators. Better interdisciplinary integration is needed to address the challenge of antimicrobial resistance. Improving the dialogues between the disciplines is a necessary first step in this process. Greater engagement of ecologists is needed to build a more complete understanding of the role of ecosystems in human health, and identify how human interactions with ecosystems can both contribute to, and restrict, the development of antimicrobial resistance.     

耐药菌在人-动物-环境中的传播和遗传机制

我国细菌耐药现象十分普遍,多重耐药甚至泛耐药的菌株不断出现,给公共卫生和食品安全造成了重大威胁。随着人类活动以及农业畜牧业的发展,在物理和生物作用力之下,医疗行业和养殖业对环境产生了很大的负面影响,导致养殖动物及其相关环境中存在大量的耐药基因/耐药细菌。医疗行业、动物养殖、自然环境三者在耐药菌的传播和发展中是相互影响、互相作用的有机整体,耐药基因可以借助基因水平转移等方式在人、动物和环境中循环传播,增加了人类摄入耐药基因的风险。面对此类公共卫生问题,传统单一化的卫生工作系统已很难有效地解决这类挑战,急需多学科、多领域的合作来共同应对。文中对我国临床、动物和环境中的细菌耐药现状以及耐药菌在其中的传播和遗传机制进行了综述,以期为细菌耐药研究提供参考。     

Cyanobacteria as a critical reservoir of the environmental antimicrobial resistome

Antimicrobial resistance (AMR) is predicted to cause a worldwide annual toll of 10 million deaths by 2050. This looming public health threat has been linked to antibiotic overuse and pollution, which places selective pressures on AMR maintenance and transfer in and between microbial populations. We examined the distribution, diversity and potential mobility of AMR genes in cyanobacteria. While cyanobacteria are not pathogenic, we hypothesised that they could be a major environmental reservoir for AMR genes. Genes encoding AMR to seven antimicrobial drug classes were found in 10% of cyanobacterial genomes. AMR genes were found in 13% of freshwater, 19% of terrestrial, 34% of symbiotic, 2% of thermal spring, and 3% of marine genomes. AMR genes were found in five cyanobacterial orders with 23% of Nostocales and 8% of Oscillatoriales strains containing AMR genes. The most frequently observed alleles were ansamycin resistance genes, which were present in 7% of strains. AMR genes responsible for resistance to broad-spectrum β-lactams, chloramphenicols, tetracyclines, macrolides, and aminoglycosides were associated with mobile genetic elements or plasmid replicons or both. These results suggest that cyanobacteria are an extensive reservoir, and potential vector, for AMR genes in diverse terrestrial and aquatic habitats.     

Aquatic systems: maintaining, mixing and mobilising antimicrobial resistance?

Bacteria showing antimicrobial resistance (AMR) pose a significant global healthcare problem. Although many mechanisms conferring AMR are understood, the ecological processes facilitating its persistence and spread are less well characterised. Aquatic systems represent an important milieu for the environmental release, mixing, persistence and spread of AMR bacteria and resistance genes associated with horizontally transferable genetic elements. Additionally, owing to the use and discharge of antimicrobials and biocides, and the accumulation and abundance of other pollutants, mechanisms that confer AMR might evolve in aquatic systems. In this review, we hypothesise that aquatic systems have an important ecological and evolutionary role in driving the persistence, emergence and spread of AMR, which could have consequences when attempting to reduce its occurrence in clinical settings.     

同一个世界 同一个健康

随着工业化和城镇化水平的持续提高,人类的生活方式发生了翻天覆地的变化,在传统因素依然制约人类健康的同时,食源性疾病与营养结构不合理、畜禽养殖方式转变与宠物快速发展带来人与动物关系深刻变化、生态环境与居住环境变化等非传统因素,对人类健康的制约凸显。面对这些人类健康的新挑战,我们必须因应时代变化,在大力发展医疗卫生事业的同时,树立营养健康、动物健康、环境健康三位一体的现代健康新理念。努力提高营养健康水平,以宠物健康为新的关注点高度重视动物健康,以人居、社区环境为重点营造健康生态环境,建立起现代健康新模式。     

Phenotypic and genotypic profile of clinical and animal multidrug‐resistant Salmonella enterica isolates from Mexico

Aims

The objective of this study was to obtain a phenotypic and genotypic profile of Salmonella enterica including multidrug‐resistant (MDR) isolates from food‐producing animals and clinical isolates, as well as their genetic relatedness in two different States of Mexico (Jalisco and State of Mexico).

Methods and Results

A total of 243 isolates were evaluated in terms of antimicrobial resistance (AMR) and related genes through a disk diffusion method and PCR respectively; we found 16 MDR isolates, all of them harbouring the bla_CMY gene but not qnr genes, these isolates represent less than 10% of the collection. The pulsed‐field gel electrophoresis revealed a higher genotypic similitude within isolates of State of Mexico than Jalisco.

Conclusions

A low percentage of Salmonella isolates were resistant to relevant antibiotics in human health, nevertheless, the AMR and involved genes were similar despite the different serovars and origin of the isolates.

Significance and Impact of the Study

This investigation provided an insight of the current status of AMR of Salmonella isolates in two States of Mexico and pinpoint the genes involved in AMR and their epidemiological relationship, the information could help to determine an adequate therapy in human and veterinary medicine.     

A curated data resource of 214K metagenomes for characterization of the global antimicrobial resistome

The growing threat of antimicrobial resistance (AMR) calls for new epidemiological surveillance methods, as well as a deeper understanding of how antimicrobial resistance genes (ARGs) have been transmitted around the world. The large pool of sequencing data available in public repositories provides an excellent resource for monitoring the temporal and spatial dissemination of AMR in different ecological settings. However, only a limited number of research groups globally have the computational resources to analyze such data. We retrieved 442 Tbp of sequencing reads from 214,095 metagenomic samples from the European Nucleotide Archive (ENA) and aligned them using a uniform approach against ARGs and 16S/18S rRNA genes. Here, we present the results of this extensive computational analysis and share the counts of reads aligned. Over 6.76∙10⁸ read fragments were assigned to ARGs and 3.21∙10⁹ to rRNA genes, where we observed distinct differences in both the abundance of ARGs and the link between microbiome and resistome compositions across various sampling types. This collection is another step towards establishing global surveillance of AMR and can serve as a resource for further research into the environmental spread and dynamic changes of ARGs.

The growing threat of antimicrobial resistance (AMR) calls for new epidemiological surveillance methods and a deeper understanding of how resistance genes are transmitted around the world. This study presents a large-scale remapping of sequencing reads of publicly available metagenomic datasets that can be used to monitor the global prevalence of AMR genes.     

抗生素抗性基因的生态风险研究进展

自抗生素被发现和使用以来,其在人类和动物疾病预防与治疗、提高动物生产等方面均发挥了重要作用。但抗生素的批量生产及大量应用,特别是在养殖业和临床医疗上的滥用,导致抗生素抗性基因(ARGs)在环境中普遍存在,其借助质粒、转座子、整合子等可移动元件通过接合、转座、转化等方式在环境中广泛传播,导致微生物药性不断增强,对人类健康和生态安全造成严重威胁。当前,ARGs对人类健康的影响已受到高度关注,但有关ARGs在环境中的生态风险研究还相对薄弱。本文综述了ARGs污染的现状及其生态风险,并对该领域中未来研究重点进行了展望,以期为今后抗性基因的研究和生态防控提供参考。     

A special report on India's biotech scenario: Advancement in biopharmaceutical and health care sectors

India's biotechnology industry has been growing towards new heights in conjunction with the recent economic outburst. The country has the potential to revolutionize biopharmaceutical and healthcare sectors. In this review, we have highlighted the achievements of India's biotechnology industry, especially biopharmaceutical and healthcare sectors that include therapeutics, diagnostics, stem cell research, human healthcare related bioinformatics and animal health care. We have also described regulatory mechanisms involved in India's health care biotech including manpower development.     

高通量测序技术在细菌耐药中的应用

细菌耐药已成为威胁全球人类公共健康的重要因素之一,快速、准确明确细菌耐药的特性、机制及传播特征对疾病治疗及控制耐药菌的传播具有重要意义。高通量测序技术可以同时平行检测多个基因序列的状态,已广泛应用于细菌耐药检测。目前高通量测序技术在细菌耐药领域的应用主要有:全基因组测序技术、目标区域测序技术和宏基因组测序技术。所采用的测序平台主要为Illumina、Ion Torrent、BGI等二代测序和Pacific Biosciences、Oxford Nonopore 等三代测序平台。通过细菌耐药基因预测细菌耐药表型的准确性在很大程度上依赖于成熟的专业耐药基因数据库,各种通用型、特异型及隐马尔可夫模型耐药基因数据库的建立和完善,为高通量测序技术在细菌耐药领域的应用提供了坚实的基础。本文简要介绍了高通量测序技术、数据分析方法及相应测序平台在细菌耐药领域中的应用进展,并同时介绍了细菌耐药数据库的现状。     

Gene pool transmission of multidrug resistance among Campylobacter from livestock,sewage and human disease

The use of antimicrobials in human and veterinary medicine has coincided with a rise in antimicrobial resistance (AMR) in the food-borne pathogens Campylobacter jejuni and Campylobacter coli. Faecal contamination from the main reservoir hosts (livestock, especially poultry) is the principal route of human infection but little is known about the spread of AMR among source and sink populations. In particular, questions remain about how Campylobacter resistomes interact between species and hosts, and the potential role of sewage as a conduit for the spread of AMR. Here, we investigate the genomic variation associated with AMR in 168 C. jejuni and 92 C. coli strains isolated from humans, livestock and urban effluents in Spain. AMR was tested in vitro and isolate genomes were sequenced and screened for putative AMR genes and alleles. Genes associated with resistance to multiple drug classes were observed in both species and were commonly present in multidrug-resistant genomic islands (GIs), often located on plasmids or mobile elements. In many cases, these loci had alleles that were shared among C. jejuni and C. coli consistent with horizontal transfer. Our results suggest that specific antibiotic resistance genes have spread among Campylobacter isolated from humans, animals and the environment.     

Vaccines and global health

Vaccines have made a major contribution to global health in recent decades but they could do much more. In November 2011, a Royal Society discussion meeting, 'New vaccines for global health', was held in London to discuss the past contribution of vaccines to global health and to consider what more could be expected in the future. Papers presented at the meeting reviewed recent successes in the deployment of vaccines against major infections of childhood and the challenges faced in developing vaccines against some of the world's remaining major infectious diseases such as human immunodeficiency virus (HIV), malaria and tuberculosis. The important contribution that development of more effective veterinary vaccines could make to global health was also addressed. Some of the social and financial challenges to the development and deployment of new vaccines were reviewed. The latter issues were also discussed at a subsequent satellite meeting, 'Accelerating vaccine development', held at the Kavli Royal Society International Centre. Delegates at this meeting considered challenges to the more rapid development and deployment of both human and veterinary vaccines and how these might be addressed. Papers based on presentations at the discussion meeting and a summary of the main conclusions of the satellite meeting are included in this issue of Philosophical Transactions of the Royal Society B.     

Antimicrobial resistance in humans,livestock and the wider environment

Antimicrobial resistance (AMR) in humans is inter-linked with AMR in other populations, especially farm animals, and in the wider environment. The relatively few bacterial species that cause disease in humans, and are the targets of antibiotic treatment, constitute a tiny subset of the overall diversity of bacteria that includes the gut microbiota and vast numbers in the soil. However, resistance can pass between these different populations; and homologous resistance genes have been found in pathogens, normal flora and soil bacteria. Farm animals are an important component of this complex system: they are exposed to enormous quantities of antibiotics (despite attempts at reduction) and act as another reservoir of resistance genes. Whole genome sequencing is revealing and beginning to quantify the two-way traffic of AMR bacteria between the farm and the clinic. Surveillance of bacterial disease, drug usage and resistance in livestock is still relatively poor, though improving, but achieving better antimicrobial stewardship on the farm is challenging: antibiotics are an integral part of industrial agriculture and there are very few alternatives. Human production and use of antibiotics either on the farm or in the clinic is but a recent addition to the natural and ancient process of antibiotic production and resistance evolution that occurs on a global scale in the soil. Viewed in this way, AMR is somewhat analogous to climate change, and that suggests that an intergovernmental panel, akin to the Intergovernmental Panel on Climate Change, could be an appropriate vehicle to actively address the problem.     

养殖环境中抗生素抗性基因的研究进展

抗性基因在环境中的垂直及水平传播,致使抗生素耐药性成为危及人类和动物生命健康的全球性问题。动物源食品是中国美食不可或缺之物,而由于抗生素超用与滥用等行为让公众不得不关注动物源食品源头——养殖场的抗生素抗性基因环境安全问题。本文综述了养殖环境中抗生素抗性基因的研究进展,分析了养殖环境中抗生素抗性基因产生原因、传播途径以及影响因素,介绍了现有风险评估方法和控制技术,并对今后养殖环境中抗生素抗性基因的控制策略、技术及研究方向提出了建议。