Antimicrobial resistance: more than 70 years of war between humans and bacteria. - Related Documents




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409501.0000Antimicrobial 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
410110.9999What 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
409320.9999Revisiting 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
409630.9999Environmental 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
409740.9999Gain 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
406850.9999Co-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
668060.9999Antimicrobial resistance in aquaculture: Current knowledge and alternatives to tackle the problem. Aquaculture is a rapidly growing industry that currently accounts for almost half of the fish used for human consumption worldwide. Intensive and semi-intensive practices are used to produce large stocks of fish, but frequent disease outbreaks occur, and the use of antimicrobials has become a customary practice to control them. The selective pressure exerted by these drugs, which are usually present at sub-therapeutic levels for prolonged periods in the water and the sediments, provides ideal conditions for the emergence and selection of resistant bacterial strains and stimulates horizontal gene transfer. It is now widely recognized that the passage of antimicrobial resistance genes and resistant bacteria from aquatic to terrestrial animal husbandry and to the human environment and vice versa can have detrimental effects on both human and animal health and on aquatic ecosystems. A global effort must be made to cease antimicrobial overuse in aquaculture and encourage stakeholders to adopt other disease-prevention measures. Shaping a new path is crucial to containing the increasing threat of antimicrobial resistance.201829567094
409470.9999Impact 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
663980.9999Environmental 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
407090.9999Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens. Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.201830555448
4067100.9999Metal Resistance and Its Association With Antibiotic Resistance. Antibiotic resistance is recognised as a major global threat to public health by the World Health Organization. Currently, several hundred thousand deaths yearly can be attributed to infections with antibiotic-resistant bacteria. The major driver for the development of antibiotic resistance is considered to be the use, misuse and overuse of antibiotics in humans and animals. Nonantibiotic compounds, such as antibacterial biocides and metals, may also contribute to the promotion of antibiotic resistance through co-selection. This may occur when resistance genes to both antibiotics and metals/biocides are co-located together in the same cell (co-resistance), or a single resistance mechanism (e.g. an efflux pump) confers resistance to both antibiotics and biocides/metals (cross-resistance), leading to co-selection of bacterial strains, or mobile genetic elements that they carry. Here, we review antimicrobial metal resistance in the context of the antibiotic resistance problem, discuss co-selection, and highlight critical knowledge gaps in our understanding.201728528649
4197110.9999Antibiotic-resistant bacteria: a challenge for the food industry. Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed.201323035919
6641120.9999Environmental 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
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
4194140.9999Do nonclinical uses of antibiotics make a difference? An increasing range of antibacterial compounds is being used for nonclinical purposes, especially in the fields of animal husbandry and fish farming. As in human medicine, exposure to antibiotics has lead to the emergence of antibiotic-resistant bacteria in animal populations. The potential impact of antibiotic use in animals on human health and the management of clinical infections in humans is discussed in light of growing evidence to suggest that "new" resistance genes and multiresistant pathogens with increased pathogenicity are emerging in food animals as a direct consequence of antibiotic exposure.19947963441
4069150.9999Coming from the Wild: Multidrug Resistant Opportunistic Pathogens Presenting a Primary, Not Human-Linked, Environmental Habitat. The use and misuse of antibiotics have made antibiotic-resistant bacteria widespread nowadays, constituting one of the most relevant challenges for human health at present. Among these bacteria, opportunistic pathogens with an environmental, non-clinical, primary habitat stand as an increasing matter of concern at hospitals. These organisms usually present low susceptibility to antibiotics currently used for therapy. They are also proficient in acquiring increased resistance levels, a situation that limits the therapeutic options for treating the infections they cause. In this article, we analyse the most predominant opportunistic pathogens with an environmental origin, focusing on the mechanisms of antibiotic resistance they present. Further, we discuss the functions, beyond antibiotic resistance, that these determinants may have in the natural ecosystems that these bacteria usually colonize. Given the capacity of these organisms for colonizing different habitats, from clinical settings to natural environments, and for infecting different hosts, from plants to humans, deciphering their population structure, their mechanisms of resistance and the role that these mechanisms may play in natural ecosystems is of relevance for understanding the dissemination of antibiotic resistance under a One-Health point of view.202134360847
4189160.9999Antimicrobial resistance at farm level. Bacteria that are resistant to antimicrobials are widespread. This article reviews the distribution of resistant bacteria in farm environments. Humans, animals, and environmental sites are all reservoirs of bacterial communities that contain some bacteria that are susceptible to antimicrobials and others that are resistant. Farm ecosystems provide an environment in which resistant bacteria and genes can emerge, amplify and spread. Dissemination occurs via the food chain and via several other pathways. Ecological, epidemiological, molecular and mathematical approaches are being used to study the origin and expansion of the resistance problem and its relationship to antibiotic usage. The prudent and responsible use of antibiotics is an essential part of an ethical approach to improving animal health and food safety. The responsible use of antibiotics during research is vital, but to fully contribute to the containment of antimicrobial resistance 'prudent use' must also be part of good management practices at all levels of farm life.200617094710
4190170.9999Insects represent a link between food animal farms and the urban environment for antibiotic resistance traits. Antibiotic-resistant bacterial infections result in higher patient mortality rates, prolonged hospitalizations, and increased health care costs. Extensive use of antibiotics as growth promoters in the animal industry represents great pressure for evolution and selection of antibiotic-resistant bacteria on farms. Despite growing evidence showing that antibiotic use and bacterial resistance in food animals correlate with resistance in human pathogens, the proof for direct transmission of antibiotic resistance is difficult to provide. In this review, we make a case that insects commonly associated with food animals likely represent a direct and important link between animal farms and urban communities for antibiotic resistance traits. Houseflies and cockroaches have been shown to carry multidrug-resistant clonal lineages of bacteria identical to those found in animal manure. Furthermore, several studies have demonstrated proliferation of bacteria and horizontal transfer of resistance genes in the insect digestive tract as well as transmission of resistant bacteria by insects to new substrates. We propose that insect management should be an integral part of pre- and postharvest food safety strategies to minimize spread of zoonotic pathogens and antibiotic resistance traits from animal farms. Furthermore, the insect link between the agricultural and urban environment presents an additional argument for adopting prudent use of antibiotics in the food animal industry.201424705326
4188180.9999Use of antimicrobial agents in aquaculture. The aquaculture industry has grown dramatically, and plays an important role in the world's food supply chain. Antimicrobial resistance in bacteria associated with food animals receives much attention, and drug use in aquaculture is also an important issue. There are many differences between aquatic and terrestrial management systems, such as the methods used for administration of drugs. Unique problems are related to the application of drugs in aquatic environments. Residual drugs in fish products can affect people who consume them, and antimicrobials released into aquatic environments can select for resistant bacteria. Moreover, these antimicrobial-resistant bacteria, or their resistance genes, can be transferred to humans. To decrease the risks associated with the use of antimicrobials, various regulations have been developed. In addition, it is necessary to prevent bacterial diseases in aquatic animals by vaccination, to improve culture systems, and to monitor the amount of antimicrobial drugs used and the prevalence of antimicrobial-resistant bacteria.201222849275
3983190.9999Antibiotic resistance genes in bacteria: Occurrence, spread, and control. The production and use of antibiotics are becoming increasingly common worldwide, and the problem of antibiotic resistance is increasing alarmingly. Drug-resistant infections threaten human life and health and impose a heavy burden on the global economy. The origin and molecular basis of bacterial resistance is the presence of antibiotic resistance genes (ARGs). Investigations on ARGs mostly focus on the environments in which antibiotics are frequently used, such as hospitals and farms. This literature review summarizes the current knowledge of the occurrence of antibiotic-resistant bacteria in nonclinical environments, such as air, aircraft wastewater, migratory bird feces, and sea areas in-depth, which have rarely been involved in previous studies. Furthermore, the mechanism of action of plasmid and phage during horizontal gene transfer was analyzed, and the transmission mechanism of ARGs was summarized. This review highlights the new mechanisms that enhance antibiotic resistance and the evolutionary background of multidrug resistance; in addition, some promising points for controlling or reducing the occurrence and spread of antimicrobial resistance are also proposed.202134651331