Gut microbiome in the emergence of antibiotic-resistant bacterial pathogens. - Related Documents




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402601.0000Gut 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
402811.0000Horizontal transfer of antibiotic resistance genes in the human gut microbiome. Infections caused by antibiotic-resistant bacteria are a major threat to public health. The pathogens causing these infections can acquire antibiotic resistance genes in a process termed horizontal gene transfer (HGT). HGT is a common event in the human gut microbiome, that is, the microbial ecosystem of the human intestinal tract. HGT in the gut microbiome can occur via different mechanisms of which transduction and conjugation have been best characterised. Novel bioinformatic tools and experimental approaches have been developed to determine the association of antibiotic resistance genes with their microbial hosts and to quantify the extent of HGT in the gut microbiome. Insights from studies into HGT in the gut microbiome may lead to the development of novel interventions to minimise the spread of antibiotic resistance genes among commensals and opportunistic pathogens.202032143027
402720.9999Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome. A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.202235332832
410130.9999What 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
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
410250.9999Forces shaping the antibiotic resistome. Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance.201425213620
400460.9999Diverse 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
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
409680.9999Environmental 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
400590.9999Metagenomic-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
6704100.9999Gut microbiota research nexus: One Health relationship between human, animal, and environmental resistomes. The emergence and rapid spread of antimicrobial resistance is of global public health concern. The gut microbiota harboring diverse commensal and opportunistic bacteria that can acquire resistance via horizontal and vertical gene transfers is considered an important reservoir and sink of antibiotic resistance genes (ARGs). In this review, we describe the reservoirs of gut ARGs and their dynamics in both animals and humans, use the One Health perspective to track the transmission of ARG-containing bacteria between humans, animals, and the environment, and assess the impact of antimicrobial resistance on human health and socioeconomic development. The gut resistome can evolve in an environment subject to various selective pressures, including antibiotic administration and environmental and lifestyle factors (e.g., diet, age, gender, and living conditions), and interventions through probiotics. Strategies to reduce the abundance of clinically relevant antibiotic-resistant bacteria and their resistance determinants in various environmental niches are needed to ensure the mitigation of acquired antibiotic resistance. With the help of effective measures taken at the national, local, personal, and intestinal management, it will also result in preventing or minimizing the spread of infectious diseases. This review aims to improve our understanding of the correlations between intestinal microbiota and antimicrobial resistance and provide a basis for the development of management strategies to mitigate the antimicrobial resistance crisis.202338818274
4025110.9999Metagenomic Insights into Transferable Antibiotic Resistance in Oral Bacteria. Antibiotic resistance is considered one of the greatest threats to global public health. Resistance is often conferred by the presence of antibiotic resistance genes (ARGs), which are readily found in the oral microbiome. In-depth genetic analyses of the oral microbiome through metagenomic techniques reveal a broad distribution of ARGs (including novel ARGs) in individuals not recently exposed to antibiotics, including humans in isolated indigenous populations. This has resulted in a paradigm shift from focusing on the carriage of antibiotic resistance in pathogenic bacteria to a broader concept of an oral resistome, which includes all resistance genes in the microbiome. Metagenomics is beginning to demonstrate the role of the oral resistome and horizontal gene transfer within and between commensals in the absence of selective pressure, such as an antibiotic. At the chairside, metagenomic data reinforce our need to adhere to current antibiotic guidelines to minimize the spread of resistance, as such data reveal the extent of ARGs without exposure to antimicrobials and the ecologic changes created in the oral microbiome by even a single dose of antibiotics. The aim of this review is to discuss the role of metagenomics in the investigation of the oral resistome, including the transmission of antibiotic resistance in the oral microbiome. Future perspectives, including clinical implications of the findings from metagenomic investigations of oral ARGs, are also considered.201627183895
4024120.9999Potential influence of antimicrobial resistance gene content in probiotic bacteria on the gut resistome ecosystems. Antimicrobial resistance (AMR) poses a substantial threat to human health. The commensal bacteria of the gut microbiome were shown to serve as a reservoir of antibiotic resistance genes (ARGs), termed the gut resistome, which has the potential to transfer horizontally to pathogens and contribute to the emergence of drug-resistant bacteria. Namely, AMR traits are generally linked with mobile genetic elements (MGEs), which apart from disseminating vertically to the progeny, may cross horizontally to the distantly related microbial species. On the other hand, while probiotics are generally considered beneficiary to human health, and are therefore widely consumed in recent years most commonly in conjunction with antibiotics, the complexities and extent of their impact on the gut microbiome and resistome have not been elucidated. By reviewing the latest studies on ARG containing commercial probiotic products and common probiotic supplement species with their actual effects on the human gut resistome, this study aims to demonstrate that their contribution to the spread of ARGs along the GI tract merits additional attention, but also indicates the changes in sampling and profiling of the gut microbiome which may allow for the more comprehensive studying of the effects of probiotics in this part of the resistome.202336819705
6639130.9999Environmental 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
4022140.9999Antibiotic resistance in the environment. Antibiotic resistance is a global health challenge, involving the transfer of bacteria and genes between humans, animals and the environment. Although multiple barriers restrict the flow of both bacteria and genes, pathogens recurrently acquire new resistance factors from other species, thereby reducing our ability to prevent and treat bacterial infections. Evolutionary events that lead to the emergence of new resistance factors in pathogens are rare and challenging to predict, but may be associated with vast ramifications. Transmission events of already widespread resistant strains are, on the other hand, common, quantifiable and more predictable, but the consequences of each event are limited. Quantifying the pathways and identifying the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance are key components to understand and manage the resistance crisis as a whole. In this Review, we present our current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic. We provide a perspective on current evidence, describe risk scenarios, discuss methods for surveillance and the assessment of potential drivers, and finally identify some actions to mitigate risks.202234737424
4014150.9999Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer. The emergence and spread of antibiotic resistance among pathogenic bacteria has been a rising problem for public health in recent decades. It is becoming increasingly recognized that not only antibiotic resistance genes (ARGs) encountered in clinical pathogens are of relevance, but rather, all pathogenic, commensal as well as environmental bacteria-and also mobile genetic elements and bacteriophages-form a reservoir of ARGs (the resistome) from which pathogenic bacteria can acquire resistance via horizontal gene transfer (HGT). HGT has caused antibiotic resistance to spread from commensal and environmental species to pathogenic ones, as has been shown for some clinically important ARGs. Of the three canonical mechanisms of HGT, conjugation is thought to have the greatest influence on the dissemination of ARGs. While transformation and transduction are deemed less important, recent discoveries suggest their role may be larger than previously thought. Understanding the extent of the resistome and how its mobilization to pathogenic bacteria takes place is essential for efforts to control the dissemination of these genes. Here, we will discuss the concept of the resistome, provide examples of HGT of clinically relevant ARGs and present an overview of the current knowledge of the contributions the various HGT mechanisms make to the spread of antibiotic resistance.201626925045
9455160.9999Prospects and Challenges of Bacteriophage Substitution for Antibiotics in Livestock and Poultry Production. The overuse and misuse of antibiotics in the livestock and poultry industry has led to the development of multi-drug resistance in animal pathogens, and antibiotic resistance genes (ARGs) in bacteria transfer from animals to humans through the consumption of animal products, posing a serious threat to human health. Therefore, the use of antibiotics in livestock production has been strictly controlled. As a result, bacteriophages have attracted increasing research interest as antibiotic alternatives, since they are natural invaders of bacteria. Numerous studies have shown that dietary bacteriophage supplementation could regulate intestinal microbial composition, enhance mucosal immunity and the physical barrier function of the intestinal tract, and play an important role in maintaining intestinal microecological stability and normal body development of animals. The effect of bacteriophages used in animals is influenced by factors such as species, dose, and duration. However, as a category of mobile genetic elements, the high frequency of gene exchange of bacteriophages also poses risks of transmitting ARGs among bacteria. Hence, we summarized the mechanism and efficacy of bacteriophage therapy, and highlighted the feasibility and challenges of bacteriophage utilization in farm animal production, aiming to provide a reference for the safe and effective application of bacteriophages as an antibiotic alternative in livestock and poultry.202438248459
4016170.9999Antimicrobial-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
4088180.9999Expanding the soil antibiotic resistome: exploring environmental diversity. Antibiotic resistance has largely been studied in the context of failure of the drugs in clinical settings. There is now growing evidence that bacteria that live in the environment (e.g. the soil) are multi-drug-resistant. Recent functional screens and the growing accumulation of metagenomic databases are revealing an unexpected density of resistance genes in the environment: the antibiotic resistome. This challenges our current understanding of antibiotic resistance and provides both barriers and opportunities for antimicrobial drug discovery.200717951101
4020190.9999Is there a role for intestinal sporobiota in the antimicrobial resistance crisis? Antimicrobial resistance (AMR) is a complex issue requiring specific, multi-sectoral measures to slow its spread. When people are exposed to antimicrobial agents, it can cause resistant bacteria to increase. This means that the use, misuse, and excessive use of antimicrobial agents exert selective pressure on bacteria, which can lead to the development of "silent" reservoirs of antimicrobial resistance genes. These genes can later be mobilized into pathogenic bacteria and contribute to the spread of AMR. Many socioeconomic and environmental factors influence the transmission and dissemination of resistance genes, such as the quality of healthcare systems, water sanitation, hygiene infrastructure, and pollution. The sporobiota is an essential part of the gut microbiota that plays a role in maintaining gut homeostasis. However, because spores are highly transmissible and can spread easily, they can be a vector for AMR. The sporobiota resistome, particularly the mobile resistome, is important for tracking, managing, and limiting the spread of antimicrobial resistance genes among pathogenic and commensal bacterial species.202439173554