Genomic and Metagenomic Approaches for Predictive Surveillance of Emerging Pathogens and Antibiotic Resistance. - Related Documents




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429801.0000Genomic and Metagenomic Approaches for Predictive Surveillance of Emerging Pathogens and Antibiotic Resistance. Antibiotic-resistant organisms (AROs) are a major concern to public health worldwide. While antibiotics have been naturally produced by environmental bacteria for millions of years, modern widespread use of antibiotics has enriched resistance mechanisms in human-impacted bacterial environments. Antibiotic resistance genes (ARGs) continue to emerge and spread rapidly. To combat the global threat of antibiotic resistance, researchers must develop methods to rapidly characterize AROs and ARGs, monitor their spread across space and time, and identify novel ARGs and resistance pathways. We review how high-throughput sequencing-based methods can be combined with classic culture-based assays to characterize, monitor, and track AROs and ARGs. Then, we evaluate genomic and metagenomic methods for identifying ARGs and biosynthetic pathways for novel antibiotics from genomic data sets. Together, these genomic analyses can improve surveillance and prediction of emerging resistance threats and accelerate the development of new antibiotic therapies to combat resistance.201931172511
400510.9999Metagenomic-based surveillance systems for antibiotic resistance in non-clinical settings. The success of antibiotics as a therapeutic agent has led to their ineffectiveness. The continuous use and misuse in clinical and non-clinical areas have led to the emergence and spread of antibiotic-resistant bacteria and its genetic determinants. This is a multi-dimensional problem that has now become a global health crisis. Antibiotic resistance research has primarily focused on the clinical healthcare sectors while overlooking the non-clinical sectors. The increasing antibiotic usage in the environment - including animals, plants, soil, and water - are drivers of antibiotic resistance and function as a transmission route for antibiotic resistant pathogens and is a source for resistance genes. These natural compartments are interconnected with each other and humans, allowing the spread of antibiotic resistance via horizontal gene transfer between commensal and pathogenic bacteria. Identifying and understanding genetic exchange within and between natural compartments can provide insight into the transmission, dissemination, and emergence mechanisms. The development of high-throughput DNA sequencing technologies has made antibiotic resistance research more accessible and feasible. In particular, the combination of metagenomics and powerful bioinformatic tools and platforms have facilitated the identification of microbial communities and has allowed access to genomic data by bypassing the need for isolating and culturing microorganisms. This review aimed to reflect on the different sequencing techniques, metagenomic approaches, and bioinformatics tools and pipelines with their respective advantages and limitations for antibiotic resistance research. These approaches can provide insight into resistance mechanisms, the microbial population, emerging pathogens, resistance genes, and their dissemination. This information can influence policies, develop preventative measures and alleviate the burden caused by antibiotic resistance.202236532424
400420.9999Diverse Distribution of Resistomes in the Human and Environmental Microbiomes. The routine therapeutic use of antibiotics has caused resistance genes to be disseminated across microbial populations. In particular, bacterial strains having antibiotic resistance genes are frequently observed in the human microbiome. Moreover, multidrug-resistant pathogens are now widely spread, threatening public health. Such genes are transferred and spread among bacteria even in different environments. Advances in high throughput sequencing technology and computational algorithms have accelerated investigation into antibiotic resistance genes of bacteria. Such studies have revealed that the antibiotic resistance genes are located close to the mobility-associated genes, which promotes their dissemination. An increasing level of information on genomic sequences of resistome should expedite research on drug-resistance in our body and environment, thereby contributing to the development of public health policy. In this review, the high prevalence of antibiotic resistance genes and their exchange in the human and environmental microbiome is discussed with respect to the genomic contents. The relationships among diverse resistomes, related bacterial species, and the antibiotics are reviewed. In addition, recent advances in bioinformatics approaches to investigate such relationships are discussed.201830532649
429930.9999Antibiotic resistance mechanism and diagnosis of common foodborne pathogens based on genotypic and phenotypic biomarkers. The emergence of antibiotic-resistant bacteria due to the overuse or inappropriate use of antibiotics has become a significant public health concern. The agri-food chain, which serves as a vital link between the environment, food, and human, contributes to the large-scale dissemination of antibiotic resistance, posing a concern to both food safety and human health. Identification and evaluation of antibiotic resistance of foodborne bacteria is a crucial priority to avoid antibiotic abuse and ensure food safety. However, the conventional approach for detecting antibiotic resistance heavily relies on culture-based methods, which are laborious and time-consuming. Therefore, there is an urgent need to develop accurate and rapid tools for diagnosing antibiotic resistance in foodborne pathogens. This review aims to provide an overview of the mechanisms of antibiotic resistance at both phenotypic and genetic levels, with a focus on identifying potential biomarkers for diagnosing antibiotic resistance in foodborne pathogens. Furthermore, an overview of advances in the strategies based on the potential biomarkers (antibiotic resistance genes, antibiotic resistance-associated mutations, antibiotic resistance phenotypes) for antibiotic resistance analysis of foodborne pathogens is systematically exhibited. This work aims to provide guidance for the advancement of efficient and accurate diagnostic techniques for antibiotic resistance analysis in the food industry.202337222539
430040.9999A review: antimicrobial resistance data mining models and prediction methods study for pathogenic bacteria. Antimicrobials have paved the way for medical and social development over the last century and are indispensable for treating infections in humans and animals. The dramatic spread and diversity of antibiotic-resistant pathogens have significantly reduced the efficacy of essentially all antibiotic classes and is a global problem affecting human and animal health. Antimicrobial resistance is influenced by complex factors such as resistance genes and dosing, which are highly nonlinear, time-lagged and multivariate coupled, and the amount of resistance data is large and redundant, making it difficult to predict and analyze. Based on machine learning methods and data mining techniques, this paper reviews (1) antimicrobial resistance data storage and analysis techniques, (2) antimicrobial resistance assessment methods and the associated risk assessment methods for antimicrobial resistance, and (3) antimicrobial resistance prediction methods. Finally, the current research results on antimicrobial resistance and the development trend are summarized to provide a systematic and comprehensive reference for the research on antimicrobial resistance.202134522024
661350.9999Approaches for characterizing and tracking hospital-associated multidrug-resistant bacteria. Hospital-associated infections are a major concern for global public health. Infections with antibiotic-resistant pathogens can cause empiric treatment failure, and for infections with multidrug-resistant bacteria which can overcome antibiotics of "last resort" there exists no alternative treatments. Despite extensive sanitization protocols, the hospital environment is a potent reservoir and vector of antibiotic-resistant organisms. Pathogens can persist on hospital surfaces and plumbing for months to years, acquire new antibiotic resistance genes by horizontal gene transfer, and initiate outbreaks of hospital-associated infections by spreading to patients via healthcare workers and visitors. Advancements in next-generation sequencing of bacterial genomes and metagenomes have expanded our ability to (1) identify species and track distinct strains, (2) comprehensively profile antibiotic resistance genes, and (3) resolve the mobile elements that facilitate intra- and intercellular gene transfer. This information can, in turn, be used to characterize the population dynamics of hospital-associated microbiota, track outbreaks to their environmental reservoirs, and inform future interventions. This review provides a detailed overview of the approaches and bioinformatic tools available to study isolates and metagenomes of hospital-associated bacteria, and their multi-layered networks of transmission.202133582841
429660.9998Twenty-first century molecular methods for analyzing antimicrobial resistance in surface waters to support One Health assessments. Antimicrobial resistance (AMR) in the environment is a growing global health concern, especially the dissemination of AMR into surface waters due to human and agricultural inputs. Within recent years, research has focused on trying to understand the impact of AMR in surface waters on human, agricultural and ecological health (One Health). While surface water quality assessments and surveillance of AMR have historically utilized culture-based methods, culturing bacteria has limitations due to difficulty in isolating environmental bacteria and the need for a priori information about the bacteria for selective isolation. The use of molecular techniques to analyze AMR at the genetic level has helped to overcome the difficulties with culture-based techniques since they do not require advance knowledge of the bacterial population and can analyze uncultivable environmental bacteria. The aim of this review is to provide an overview of common contemporary molecular methods available for analyzing AMR in surface waters, which include high throughput real-time polymerase chain reaction (HT-qPCR), metagenomics, and whole genome sequencing. This review will also feature how these methods may provide information on human and animal health risks. HT-qPCR works at the nanoliter scale, requires only a small amount of DNA, and can analyze numerous gene targets simultaneously, but may lack in analytical sensitivity and the ability to optimize individual assays compared to conventional qPCR. Metagenomics offers more detailed genomic information and taxonomic resolution than PCR by sequencing all the microbial genomes within a sample. Its open format allows for the discovery of new antibiotic resistance genes; however, the quantity of DNA necessary for this technique can be a limiting factor for surface water samples that typically have low numbers of bacteria per sample volume. Whole genome sequencing provides the complete genomic profile of a single environmental isolate and can identify all genetic elements that may confer AMR. However, a main disadvantage of this technique is that it only provides information about one bacterial isolate and is challenging to utilize for community analysis. While these contemporary techniques can quickly provide a vast array of information about AMR in surface waters, one technique does not fully characterize AMR nor its potential risks to human, animal, or ecological health. Rather, a combination of techniques (including both molecular- and culture-based) are necessary to fully understand AMR in surface waters from a One Health perspective.202133774111
400370.9998Antibiotic resistance: Global health crisis and metagenomics. Antibiotic resistance is a global problem which affects human health. The imprudent use of antibiotics (medicine, agriculture, aquaculture, and food industry) has resulted in the broader dissemination of resistance. Urban wastewater & sewage treatment plants act as the hotspot for the widespread of antimicrobial resistance. Natural environment also plays an important role in the dissemination of resistance. Mapping of antibiotic resistance genes (ARGS) in environment is essential for mitigating antimicrobial resistance (AMR) widespread. Therefore, the review article emphasizes on the application of metagenomics for the surveillance of antimicrobial resistance. Metagenomics is the next generation tool which is being used for cataloging the resistome of diverse environments. We summarize the different metagenomic tools that can be used for mining of ARGs and acquired AMR present in the metagenomic data. Also, we recommend application of targeted sequencing/ capture platform for mapping of resistome with higher specificity and selectivity.202133732632
400080.9998Biofilms as potential reservoirs of antimicrobial resistance in vulnerable settings. Antimicrobial resistance is a major global health threat, characterized by the ability of microorganisms to withstand the effects of antimicrobial agents. Biofilms, as unique microbial communities, significantly contribute to this threat. They provide a protective environment for pathogens, facilitate horizontal gene transfer, and create an ideal setting for the persistence and evolution of resistant bacteria. This issue can be particularly important in low-income settings and vulnerable communities, such as formal and informal refugee and migrant camps. These settings usually have limited access to healthcare resources and appropriate treatments, contributing to the selective pressure that promotes the survival and proliferation of resistant bacteria. Thus, biofilms formed in wastewater in these areas can play a critical role in spreading antimicrobial resistance or acting as hidden reservoirs for future outbreaks. While emerging efforts focus on detecting antibiotic resistance genes and planktonic bacteria in wastewater, biofilms may be a source of under-appreciated antimicrobial resistance, creating a significant gap in our understanding of resistance dynamics in wastewater systems. Incorporating biofilm surveillance into wastewater monitoring strategies in vulnerable settings can help develop a more comprehensive understanding of resistance transmission and more effective intervention measures in these settings.202540190753
400290.9998Targeting bioinformatics tools to study the dissemination and spread of antibiotic resistant genes in the environment and clinical settings. Antibiotic resistance has expanded as a result of the careless use of antibiotics in the medical field, the food industry, agriculture, and other industries. By means of genetic recombination between commensal and pathogenic bacteria, the microbes obtain antibiotic resistance genes (ARGs). In bacteria, horizontal gene transfer (HGT) is the main mechanism for acquiring ARGs. With the development of high-throughput sequencing, ARG sequence analysis is now feasible and widely available. Preventing the spread of AMR in the environment requires the implementation of ARGs mapping. The metagenomic technique, in particular, has helped in identifying antibiotic resistance within microbial communities. Due to the exponential growth of experimental and clinical data, significant investments in computer capacity, and advancements in algorithmic techniques, the application of machine learning (ML) algorithms to the problem of AMR has attracted increasing attention over the past five years. The review article sheds a light on the application of bioinformatics for the antibiotic resistance monitoring. The most advanced tool currently being employed to catalog the resistome of various habitats are metagenomics and metatranscriptomics. The future lies in the hands of artificial intelligence (AI) and machine learning (ML) methods, to predict and optimize the interaction of antibiotic-resistant compounds with target proteins.202539552541
6611100.9998Transmission of Antibiotic Resistant Bacteria and Genes: Unveiling the Jigsaw Pieces of a One Health Problem. Antimicrobial Resistance is one of the major Global Health challenges of the twenty-first century, and one of the World Health Organization's (WHO) top ten global health threats. The evolution of antibiotic resistance among bacterial pathogens requires urgent concerted global efforts under a One Health approach integrating human, animal, and environmental surveillance data. This is crucial to develop efficient control strategies and counteract the spread of multidrug-resistant pathogens. The studies in this Special Issue have evidenced the hidden role of less common species, unusual clones or unexplored niches in the dissemination of antimicrobial resistance between different hosts. They reinforce the need for large-scale surveillance studies tracing and tracking both antibiotic resistance and metal tolerance in different bacterial species.202032580441
9557110.9998Antimicrobial Resistance Profile by Metagenomic and Metatranscriptomic Approach in Clinical Practice: Opportunity and Challenge. The burden of bacterial resistance to antibiotics affects several key sectors in the world, including healthcare, the government, and the economic sector. Resistant bacterial infection is associated with prolonged hospital stays, direct costs, and costs due to loss of productivity, which will cause policy makers to adjust their policies. Current widely performed procedures for the identification of antibiotic-resistant bacteria rely on culture-based methodology. However, some resistance determinants, such as free-floating DNA of resistance genes, are outside the bacterial genome, which could be potentially transferred under antibiotic exposure. Metagenomic and metatranscriptomic approaches to profiling antibiotic resistance offer several advantages to overcome the limitations of the culture-based approach. These methodologies enhance the probability of detecting resistance determinant genes inside and outside the bacterial genome and novel resistance genes yet pose inherent challenges in availability, validity, expert usability, and cost. Despite these challenges, such molecular-based and bioinformatics technologies offer an exquisite advantage in improving clinicians' diagnoses and the management of resistant infectious diseases in humans. This review provides a comprehensive overview of next-generation sequencing technologies, metagenomics, and metatranscriptomics in assessing antimicrobial resistance profiles.202235625299
4094120.9998Impact of environment on transmission of antibiotic-resistant superbugs in humans and strategies to lower dissemination of antibiotic resistance. Antibiotics are the most efficient type of therapy developed in the twentieth century. From the early 1960s to the present, the rate of discovery of new and therapeutically useful classes of antibiotics has significantly decreased. As a result of antibiotic use, novel strains emerge that limit the efficiency of therapies in patients, resulting in serious consequences such as morbidity or mortality, as well as clinical difficulties. Antibiotic resistance has created major concern and has a greater impact on global health. Horizontal and vertical gene transfers are two mechanisms involved in the spread of antibiotic resistance genes (ARGs) through environmental sources such as wastewater treatment plants, agriculture, soil, manure, and hospital-associated area discharges. Mobile genetic elements have an important part in microbe selection pressure and in spreading their genes into new microbial communities; additionally, it establishes a loop between the environment, animals, and humans. This review contains antibiotics and their resistance mechanisms, diffusion of ARGs, prevention of ARG transmission, tactics involved in microbiome identification, and therapies that aid to minimize infection, which are explored further below. The emergence of ARGs and antibiotic-resistant bacteria (ARB) is an unavoidable threat to global health. The discovery of novel antimicrobial agents derived from natural products shifts the focus from chemical modification of existing antibiotic chemical composition. In the future, metagenomic research could aid in the identification of antimicrobial resistance genes in the environment. Novel therapeutics may reduce infection and the transmission of ARGs.202337589876
4031130.9998Application of genomic technologies to measure and monitor antibiotic resistance in animals. One of the richest reservoirs of antibiotic-resistant bacteria and genes, animal intestinal microbiota contributes to the spread of antibiotic resistance in the environment and, potentially, to human pathogens. Both culture-based genomic technology and culture-independent metagenomics have been developed to investigate the abundance and diversity of antibiotic resistance genes. The characteristics, strengths, limitations, and challenges of these genomic approaches are discussed in this review in the context of antibiotic resistance in animals. We also discuss the advances in single-cell genomics and its potential for surveillance of antibiotic resistance in animals.201727997690
4030140.9998The human microbiome as a reservoir of antimicrobial resistance. The gut microbiota is amongst the most densely populated microbial ecosystem on earth. While the microbiome exerts numerous health beneficial functions, the high density of micro-organisms within this ecosystem also facilitates horizontal transfer of antimicrobial resistance (AMR) genes to potential pathogenic bacteria. Over the past decades antibiotic susceptibility testing of specific indicator bacteria from the microbiome, such as Escherichia coli, has been the method of choice in most studies. These studies have greatly enlarged our understanding on the prevalence and distribution of AMR and associated risk factors. Recent studies using (functional) metagenomics, however, highlighted the unappreciated diversity of AMR genes in the human microbiome and identified genes that had not been described previously. Next to metagenomics, more targeted approaches such as polymerase chain reaction for detection and quantification of AMR genes within a population are promising, in particular for large-scale epidemiological screening. Here we present an overview of the indigenous microbiota as a reservoir of AMR genes, the current knowledge on this "resistome" and the recent and upcoming advances in the molecular diagnostic approaches to unravel this reservoir.201323616784
9457150.9998Exploring the role of gut microbiota in antibiotic resistance and prevention. BACKGROUND/INTRODUCTION: Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials. MAIN BODY: This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment. DISCUSSION: Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.202540096354
6702160.9998Reservoirs of antimicrobial resistance in the context of One Health. The emergence and spread of antimicrobial resistance (AMR) and resistant bacteria, are a global public health challenge. Through horizontal gene transfer, potential pathogens can acquire antimicrobial resistance genes (ARGs) that can subsequently be spread between human, animal, and environmental reservoirs. To understand the dissemination of ARGs and linked microbial taxa, it is necessary to map the resistome within different microbial reservoirs. By integrating knowledge on ARGs in the different reservoirs, the One Health approach is crucial to our understanding of the complex mechanisms and epidemiology of AMR. Here, we highlight the latest insights into the emergence and spread of AMR from the One Health perspective, providing a baseline of understanding for future scientific investigations into this constantly growing global health threat.202336913905
4087170.9998Next-generation approaches to understand and combat the antibiotic resistome. Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.201728392565
6520180.9998Antimicrobial Resistance in the Environment: Towards Elucidating the Roles of Bioaerosols in Transmission and Detection of Antibacterial Resistance Genes. Antimicrobial resistance (AMR) is continuing to grow across the world. Though often thought of as a mostly public health issue, AMR is also a major agricultural and environmental problem. As such, many researchers refer to it as the preeminent One Health issue. Aerial transport of antimicrobial-resistant bacteria via bioaerosols is still poorly understood. Recent work has highlighted the presence of antibiotic resistance genes in bioaerosols. Emissions of AMR bacteria and genes have been detected from various sources, including wastewater treatment plants, hospitals, and agricultural practices; however, their impacts on the broader environment are poorly understood. Contextualizing the roles of bioaerosols in the dissemination of AMR necessitates a multidisciplinary approach. Environmental factors, industrial and medical practices, as well as ecological principles influence the aerial dissemination of resistant bacteria. This article introduces an ongoing project assessing the presence and fate of AMR in bioaerosols across Canada. Its various sub-studies include the assessment of the emissions of antibiotic resistance genes from many agricultural practices, their long-distance transport, new integrative methods of assessment, and the creation of dissemination models over short and long distances. Results from sub-studies are beginning to be published. Consequently, this paper explains the background behind the development of the various sub-studies and highlight their shared aspects.202235884228
6676190.9998Genomic interplay in bacterial communities: implications for growth promoting practices in animal husbandry. The discovery of antibiotics heralded the start of a "Golden Age" in the history of medicine. Over the years, the use of antibiotics extended beyond medical practice into animal husbandry, aquaculture and agriculture. Now, however, we face the worldwide threat of diseases caused by pathogenic bacteria that are resistant to all existing major classes of antibiotic, reflecting the possibility of an end to the antibiotic era. The seriousness of the threat is underscored by the severely limited production of new classes of antibiotics. Evolution of bacteria resistant to multiple antibiotics results from the inherent genetic capability that bacteria have to adapt rapidly to changing environmental conditions. Consequently, under antibiotic selection pressures, bacteria have acquired resistance to all classes of antibiotics, sometimes very shortly after their introduction. Arguably, the evolution and rapid dissemination of multiple drug resistant genes en-masse across microbial pathogens is one of the most serious threats to human health. In this context, effective surveillance strategies to track the development of resistance to multiple antibiotics are vital to managing global infection control. These surveillance strategies are necessary for not only human health but also for animal health, aquaculture and plant production. Shortfalls in the present surveillance strategies need to be identified. Raising awareness of the genetic events that promote co-selection of resistance to multiple antimicrobials is an important prerequisite to the design and implementation of molecular surveillance strategies. In this review we will discuss how lateral gene transfer (LGT), driven by the use of low-dose antibiotics in animal husbandry, has likely played a significant role in the evolution of multiple drug resistance (MDR) in Gram-negative bacteria and has complicated molecular surveillance strategies adopted for predicting imminent resistance threats.201425161648