Impact of environment on transmission of antibiotic-resistant superbugs in humans and strategies to lower dissemination of antibiotic resistance. - Related Documents




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409401.0000Impact 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
409311.0000Revisiting Antibiotic Resistance Spreading in Wastewater Treatment Plants - Bacteriophages as a Much Neglected Potential Transmission Vehicle. The spread of antibiotic resistance is currently a major threat to health that humanity is facing today. Novel multidrug and pandrug resistant bacteria are reported on a yearly basis, while the development of novel antibiotics is lacking. Focus to limit the spread of antibiotic resistance by reducing the usage of antibiotics in health care, veterinary applications, and meat production, have been implemented, limiting the exposure of pathogens to antibiotics, thus lowering the selection of resistant strains. Despite these attempts, the global resistance has increased significantly. A recent area of focus has been to limit the spread of resistance through wastewater treatment plants (WWTPs), serving as huge reservoirs of microbes and resistance genes. While being able to quite efficiently reduce the presence of resistant bacteria entering any of the final products of WWTPs (e.g., effluent water and sludge), the presence of resistance genes in other formats (mobile genetic elements, bacteriophages) has mainly been ignored. Recent data stress the importance of transduction in WWTPs as a mediator of resistance spread. Here we examine the current literature in the role of WWTPs as reservoirs and hotspots of antibiotic resistance with a specific focus on bacteriophages as mediators of genetic exchange.201729209304
664120.9999Environmental antibiotics and resistance genes as emerging contaminants: Methods of detection and bioremediation. In developing countries, the use of antibiotics has helped to reduce the mortality rate by minimizing the deaths caused by pathogenic infections, but the costs of antibiotic contamination remain a major concern. Antibiotics are released into the environment, creating a complicated environmental problem. Antibiotics are used in human, livestock and agriculture, contributing to its escalation in the environment. Environmental antibiotics pose a range of risks and have significant effects on human and animal health. Nevertheless, this is the result of the development of antibiotic-resistant and multi-drug-resistant bacteria. In the area of health care, animal husbandry and crop processing, the imprudent use of antibiotic drugs produces antibiotic-resistant bacteria. This threat is the deepest in the developing world, with an estimated 700,000 people suffering from antibiotic-resistant infections each year. The study explores how bacteria use a wide variety of antibiotic resistance mechanism and how these approaches have an impact on the environment and on our health. The paper focuses on the processes by which antibiotics degrade, the health effects of these emerging contaminants, and the tolerance of bacteria to antibiotics.202134841318
409730.9999Gain and loss of antibiotic resistant genes in multidrug resistant bacteria: One Health perspective. The emergence of multidrug resistance (MDR) has become a global health threat due to the increasing unnecessary use of antibiotics. Multidrug resistant bacteria occur mainly by accumulating resistance genes on mobile genetic elements (MGEs), made possible by horizontal gene transfer (HGT). Humans and animal guts along with natural and engineered environments such as wastewater treatment plants and manured soils have proven to be the major reservoirs and hotspots of spreading antibiotic resistance genes (ARGs). As those environments support the dissemination of MGEs through the complex interactions that take place at the human-animal-environment interfaces, a growing One Health challenge is for multiple sectors to communicate and work together to prevent the emergence and spread of MDR bacteria. However, maintenance of ARGs in a bacterial chromosome and/or plasmids in the environments might place energy burdens on bacterial fitness in the absence of antibiotics, and those unnecessary ARGs could eventually be lost. This review highlights and summarizes the current investigations into the gain and loss of ARG genes in MDR bacteria among human-animal-environment interfaces. We also suggest alternative treatments such as combinatory therapies or sequential use of different classes of antibiotics/adjuvants, treatment with enzyme-inhibitors, and phage therapy with antibiotics to solve the MDR problem from the perspective of One Health issues.202133877574
402640.9999Gut microbiome in the emergence of antibiotic-resistant bacterial pathogens. The human gastrointestinal tract is home to a complex and dynamic community of microorganisms known as gut microbiota, which provide the host with important metabolic, signaling, and immunomodulatory functions. Both the commensal and pathogenic members of the gut microbiome serve as reservoirs of antimicrobial-resistance genes (ARG), which can cause potential health threats to the host and can transfer the ARGs to the susceptible microbes and into the environment. Antimicrobial resistance is becoming a major burden on human health and is widely recognized as a global challenge. The diversity and abundance of ARGs in the gut microbiome are variable and depend on the exposure to healthcare-associated antibiotics, usage of antibiotics in veterinary and agriculture, and the migration of the population. The transfer frequency of the ARGs through horizontal gene transfer (HGT) with the help of mobile genetic elements (MGEs) like plasmids, transposons, or phages is much higher among bacteria living in the GI tract compared to other microbial ecosystems. HGT in gut bacteria is facilitated through multiple gene transfer mechanisms, including transformation, conjugation, transduction, and vesicle fusion. It is the need of the hour to implement strict policies to limit indiscriminate antibiotic usage when needed. Developing rapid diagnostic tests for resistance determination and alternatives to antibiotics like vaccination, probiotics, and bacteriophage therapy should have the highest priority in the research and development sectors. Collective actions for sustainable development against resistant pathogens by promoting endogenous gut microbial growth and diversity through interdisciplinary research and findings are key to overcoming the current antimicrobial resistance crisis.202236280316
409550.9999Antimicrobial resistance: more than 70 years of war between humans and bacteria. Development of antibiotic resistance in bacteria is one of the major issues in the present world and one of the greatest threats faced by mankind. Resistance is spread through both vertical gene transfer (parent to offspring) as well as by horizontal gene transfer like transformation, transduction and conjugation. The main mechanisms of resistance are limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. The highest quantities of antibiotic concentrations are usually found in areas with strong anthropogenic pressures, for example medical source (e.g., hospitals) effluents, pharmaceutical industries, wastewater influents, soils treated with manure, animal husbandry and aquaculture (where antibiotics are generally used as in-feed preparations). Hence, the strong selective pressure applied by antimicrobial use has forced microorganisms to evolve for survival. The guts of animals and humans, wastewater treatment plants, hospital and community effluents, animal husbandry and aquaculture runoffs have been designated as "hotspots for AMR genes" because the high density of bacteria, phages, and plasmids in these settings allows significant genetic exchange and recombination. Evidence from the literature suggests that the knowledge of antibiotic resistance in the population is still scarce. Tackling antimicrobial resistance requires a wide range of strategies, for example, more research in antibiotic production, the need of educating patients and the general public, as well as developing alternatives to antibiotics (briefly discussed in the conclusions of this article).202032954887
663960.9999Environmental Spread of Antibiotic Resistance. Antibiotic resistance represents a global health concern. Soil, water, livestock and plant foods are directly or indirectly exposed to antibiotics due to their agricultural use or contamination. This selective pressure has acted synergistically to bacterial competition in nature to breed antibiotic-resistant (AR) bacteria. Research over the past few decades has focused on the emergence of AR pathogens in food products that can cause disease outbreaks and the spread of antibiotic resistance genes (ARGs), but One Health approaches have lately expanded the focus to include commensal bacteria as ARG donors. Despite the attempts of national and international authorities of developed and developing countries to reduce the over-prescription of antibiotics to humans and the use of antibiotics as livestock growth promoters, the selective flow of antibiotic resistance transmission from the environment to the clinic (and vice-versa) is increasing. This review focuses on the mechanisms of ARG transmission and the hotspots of antibiotic contamination resulting in the subsequent emergence of ARGs. It follows the transmission of ARGs from farm to plant and animal food products and provides examples of the impact of ARG flow to clinical settings. Understudied and emerging antibiotic resistance selection determinants, such as heavy metal and biocide contamination, are also discussed here.202134071771
400570.9999Metagenomic-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
410180.9999What Is the Role of the Environment in the Emergence of Novel Antibiotic Resistance Genes? A Modeling Approach. It is generally accepted that intervention strategies to curb antibiotic resistance cannot solely focus on human and veterinary medicine but must also consider environmental settings. While the environment clearly has a role in transmission of resistant bacteria, its role in the emergence of novel antibiotic resistance genes (ARGs) is less clear. It has been suggested that the environment constitutes an enormous recruitment ground for ARGs to pathogens, but its extent is practically unknown. We have constructed a model framework for resistance emergence and used available quantitative data on relevant processes to identify limiting steps in the appearance of ARGs in human pathogens. We found that in a majority of possible scenarios, the environment would only play a minor role in the emergence of novel ARGs. However, the uncertainty is enormous, highlighting an urgent need for more quantitative data. Specifically, more data is most needed on the fitness costs of ARG carriage, the degree of dispersal of resistant bacteria from the environment to humans, and the rates of mobilization and horizontal transfer of ARGs. This type of data is instrumental to determine which processes should be targeted for interventions to curb development and transmission of ARGs in the environment.202134792330
406890.9999Co-selection for antibiotic resistance by environmental contaminants. The environment is increasingly recognised as a hotspot for the selection and dissemination of antibiotic resistant bacteria and antibiotic resistance genes. These can be selected for by antibiotics and non-antibiotic agents (such as metals and biocides), with the evidence to support this well established by observational and experimental studies. However, there is emerging evidence to suggest that plant protection products (such as herbicides), and non-antibiotic drugs (such as chemotherapeutic agents), can also co-select for antibiotic resistance. This review aims to provide an overview of four classes of non-antibiotic agents (metals, biocides, plant protection products, and non-antibiotic drugs) and how they may co-select for antibiotic resistance, with a particular focus on the environment. It also aims to identify key knowledge gaps that should be addressed in future work, to better understand these potential co-selective agents.202439843965
6468100.9999Impact of anthropogenic activities on the dissemination of antibiotic resistance across ecological boundaries. Antibiotics are considered to be one of the major medical breakthroughs in history. Nonetheless, over the past four decades, antibiotic resistance has reached alarming levels worldwide and this trend is expected to continue to increase, leading some experts to forecast the coming of a 'post-antibiotic' era. Although antibiotic resistance in pathogens is traditionally linked to clinical environments, there is a rising concern that the global propagation of antibiotic resistance is also associated with environmental reservoirs that are linked to anthropogenic activities such as animal husbandry, agronomic practices and wastewater treatment. It is hypothesized that the emergence and dissemination of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) within and between environmental microbial communities can ultimately contribute to the acquisition of antibiotic resistance in human pathogens. Nonetheless, the scope of this phenomenon is not clear due to the complexity of microbial communities in the environment and methodological constraints that limit comprehensive in situ evaluation of microbial genomes. This review summarizes the current state of knowledge regarding antibiotic resistance in non-clinical environments, specifically focusing on the dissemination of antibiotic resistance across ecological boundaries and the contribution of this phenomenon to global antibiotic resistance.201728258226
6487110.9999An evaluation of conventional and nature-based technologies for controlling antibiotic-resistant bacteria and antibiotic-resistant genes in wastewater treatment plants. Antibiotic resistance is a globally recognized health concern which leads to longer hospital stays, increased morbidity, increased mortality, and higher medical costs. Understanding how antibiotic resistance persists and exchanges in environmental systems like soil, water, and wastewater are critically important for understanding the emergence of pathogens with new resistance profiles and the subsequent exposure of people who indirectly/directly come in contact with these pathogens. There are concerns about the widespread application of prophylactic antibiotics in the clinical and agriculture sectors, as well as chemicals/detergents used in food and manufacturing industries, especially the quaternary ammonium compounds which have been found responsible for the generation of resistant genes in water and soil. The rates of horizontal gene transfer increase where there is a lack of proper water/wastewater infrastructure, high antibiotic manufacturing industries, or endpoint users - such as hospitals and intensive agriculture. Conventional wastewater treatment technologies are often inefficient in the reduction of ARB/ARGs and provide the perfect combination of conditions for the development of antibiotic resistance. The wastewater discharged from municipal facilities may therefore be enriched with bacterial communities/pathogens and provide a suitable environment (due to the presence of nutrients and other pollutants) to enhance the transfer of antibiotic resistance. However, facilities with tertiary treatment (either traditional/emerging technologies) provide higher rates of reduction. This review provides a synthesis of the current understanding of wastewater treatment and antibiotic resistance, examining the drivers that may accelerate their possible transmission to a different environment, and highlighting the need for tertiary technologies used in treatment plants for the reduction of resistant bacteria/genes.202438286289
6514120.9999Review of antibiotic-resistant bacteria and antibiotic resistance genes within the one health framework. Background: The interdisciplinary One Health (OH) approach recognizes that human, animal, and environmental health are all interconnected. Its ultimate goal is to promote optimal health for all through the exploration of these relationships. Antibiotic resistance (AR) is a public health challenge that has been primarily addressed within the context of human health and clinical settings. However, it has become increasingly evident that antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) that confer resistance are transmitted and circulated within humans, animals, and the environment. Therefore, to effectively address this issue, antibiotic resistance must also be considered an environmental and livestock/wildlife problem. Objective: This review was carried out to provide a broad overview of the existence of ARB and ARGs in One Health settings. Methods: Relevant studies that placed emphasis on ARB and ARGs were reviewed and key findings were accessed that illustrate the importance of One Health as a measure to tackle growing public and environmental threats. Results: In this review, we delve into the complex interplay of the three components of OH in relation to ARB and ARGs. Antibiotics used in animal husbandry and plants to promote growth, treat, and prevent infectious diseases lead to the development of antibiotic-resistant bacteria in animals. These bacteria are transmitted from animals to humans through food and environmental exposure. The environment plays a critical role in the circulation and persistence of antibiotic-resistant bacteria and genes, posing a significant threat to human and animal health. This article also highlights how ARGs are spread in the environment through the transfer of genetic material between bacteria. This transfer can occur naturally or through human activities such as the use of antibiotics in agriculture and waste management practices. Conclusion: It is important to integrate the One Health approach into the public health system to effectively tackle the emergence and spread of ARB and genes that code for resistance to different antibiotics.202438371518
4073130.9999The Spread of Antibiotic Resistance Genes In Vivo Model. Infections caused by antibiotic-resistant bacteria are a major public health threat. The emergence and spread of antibiotic resistance genes (ARGs) in the environment or clinical setting pose a serious threat to human and animal health worldwide. Horizontal gene transfer (HGT) of ARGs is one of the main reasons for the dissemination of antibiotic resistance in vitro and in vivo environments. There is a consensus on the role of mobile genetic elements (MGEs) in the spread of bacterial resistance. Most drug resistance genes are located on plasmids, and the spread of drug resistance genes among microorganisms through plasmid-mediated conjugation transfer is the most common and effective way for the spread of multidrug resistance. Experimental studies of the processes driving the spread of antibiotic resistance have focused on simple in vitro model systems, but the current in vitro protocols might not correctly reflect the HGT of antibiotic resistance genes in realistic conditions. This calls for better models of how resistance genes transfer and disseminate in vivo. The in vivo model can better mimic the situation that occurs in patients, helping study the situation in more detail. This is crucial to develop innovative strategies to curtail the spread of antibiotic resistance genes in the future. This review aims to give an overview of the mechanisms of the spread of antibiotic resistance genes and then demonstrate the spread of antibiotic resistance genes in the in vivo model. Finally, we discuss the challenges in controlling the spread of antibiotic resistance genes and their potential solutions.202235898691
4096140.9999Environmental hotspots for antibiotic resistance genes. Bacterial resistance toward broad-spectrum antibiotics has become a major concern in recent years. The threat posed by the infectious bacteria and the pace with which resistance determinants are transmitted needs to be deciphered. Soil and water contain unique and diverse microbial communities as well as pools of naturally occurring antibiotics resistant genes. Overuse of antibiotics along with poor sanitary practices expose these indigenous microbial communities to antibiotic resistance genes from other bacteria and accelerate the process of acquisition and dissemination. Clinical settings, where most antibiotics are prescribed, are hypothesized to serve as a major hotspot. The predisposition of the surrounding environments to a pool of antibiotic-resistant bacteria facilitates rapid antibiotic resistance among the indigenous microbiota in the soil, water, and clinical environments via horizontal gene transfer. This provides favorable conditions for the development of more multidrug-resistant pathogens. Limitations in detecting gene transfer mechanisms have likely left us underestimating the role played by the surrounding environmental hotspots in the emergence of multidrug-resistant bacteria. This review aims to identify the major drivers responsible for the spread of antibiotic resistance and hotspots responsible for the acquisition of antibiotic resistance genes.202134180594
6642150.9999A Review of Current Bacterial Resistance to Antibiotics in Food Animals. The overuse of antibiotics in food animals has led to the development of bacterial resistance and the widespread of resistant bacteria in the world. Antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in food animals are currently considered emerging contaminants, which are a serious threat to public health globally. The current situation of ARB and ARGs from food animal farms, manure, and the wastewater was firstly covered in this review. Potential risks to public health were also highlighted, as well as strategies (including novel technologies, alternatives, and administration) to fight against bacterial resistance. This review can provide an avenue for further research, development, and application of novel antibacterial agents to reduce the adverse effects of antibiotic resistance in food animal farms.202235633728
4004160.9999Diverse 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
6640170.9999The incidence of antibiotic resistance within and beyond the agricultural ecosystem: A concern for public health. The agricultural ecosystem creates a platform for the development and dissemination of antimicrobial resistance, which is promoted by the indiscriminate use of antibiotics in the veterinary, agricultural, and medical sectors. This results in the selective pressure for the intrinsic and extrinsic development of the antimicrobial resistance phenomenon, especially within the aquaculture-animal-manure-soil-water-plant nexus. The existence of antimicrobial resistance in the environment has been well documented in the literature. However, the possible transmission routes of antimicrobial agents, their resistance genes, and naturally selected antibiotic-resistant bacteria within and between the various niches of the agricultural environment and humans remain poorly understood. This study, therefore, outlines an overview of the discovery and development of commonly used antibiotics; the timeline of resistance development; transmission routes of antimicrobial resistance in the agro-ecosystem; detection methods of environmental antimicrobial resistance determinants; factors involved in the evolution and transmission of antibiotic resistance in the environment and the agro-ecosystem; and possible ways to curtail the menace of antimicrobial resistance.202032710495
4016180.9999Antimicrobial-induced horizontal transfer of antimicrobial resistance genes in bacteria: a mini-review. The emergence and spread of antimicrobial resistance (AMR) among pathogenic bacteria constitute an accelerating crisis for public health. The selective pressures caused by increased use and misuse of antimicrobials in medicine and livestock production have accelerated the overall selection of resistant bacteria. In addition, horizontal gene transfer (HGT) plays an important role in the spread of resistance genes, for example mobilizing reservoirs of AMR from commensal bacteria into pathogenic ones. Antimicrobials, besides antibacterial function, also result in undesirable effects in the microbial populations, including the stimulation of HGT. The main aim of this narrative review was to present an overview of the current knowledge of the impact of antimicrobials on HGT in bacteria, including the effects of transformation, transduction and conjugation, as well as other less well-studied mechanisms of HGT. It is widely accepted that conjugation plays a major role in the spread of AMR in bacteria, and the focus of this review is therefore mainly on the evidence provided that antimicrobial treatment affects this process. Other mechanisms of HGT have so far been deemed less important in this respect; however, recent discoveries suggest their role may be larger than previously thought, and the review provides an update on the rather limited knowledge currently available regarding the impact of antimicrobial treatment on these processes as well. A conclusion from the review is that there is an urgent need to investigate the mechanisms of antimicrobial-induced HGT, since this will be critical for developing new strategies to combat the spread of AMR.202234894259
4015190.9999Bacteriophages as Environmental Reservoirs of Antibiotic Resistance. Although antibiotic resistance represents a significant and growing public health concern, the contribution of bacteriophages (phages) to the mobilization of antibiotic resistance genes (ARGs) in the environment has not been extensively studied. Recent studies, however, suggest that phages play an important role in the acquisition, maintenance, and spread of ARGs than previously expected. This Opinion article offers an update on the contribution of phages to environmental antibiotic resistance. A better understanding of the mechanisms and factors that promote antibiotic resistance may significantly contribute to the implementation of control strategies.201930905524