Blocking horizontal transfer of antibiotic resistance genes: an effective strategy in combating antibiotic resistance. - Related Documents




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644401.0000Blocking horizontal transfer of antibiotic resistance genes: an effective strategy in combating antibiotic resistance. Antimicrobial resistance (AMR) poses a significant public health threat, with emerging and novel forms of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB) potentially crossing international borders and challenging the global health systems. The rate of development of antibiotic resistance surpasses the development of new antibiotics. Consequently, there is a growing threat of bacteria acquiring resistance even to newer antibiotics further complicating the treatment of bacterial infections. Horizontal gene transfer (HGT) is the key mechanism for the spread of antibiotic resistance in bacteria through the processes of conjugation, transformation, and transduction. Several compounds, other than antibiotics, have also been shown to promote HGT of ARGs. Given the crucial role of HGT in the dissemination of ARGs, inhibition of HGT is a key strategy to mitigate AMR. Therefore, this review explores the contribution of HGT in bacterial evolution, identifies specific hotspots andhighlights the role of HGT inhibitors in impeding the spread of ARGs. By specifically focusing on the HGT mechanism and its inhibition, these inhibitors offer a highly promising approach to combating AMR.202540207493
401310.9999Correlation between Exogenous Compounds and the Horizontal Transfer of Plasmid-Borne Antibiotic Resistance Genes. The global spread of antibiotic resistance has posed a serious threat to public healthcare and undermined decades of progress made in the fight against bacterial infections. It has been demonstrated that the lack of novel effective antibiotics and rapid spread of antibiotic resistance genes via horizontal transfer in the ecosystem are mainly responsible for this crisis. Notably, plasmid-mediated horizontal transfer of antibiotic resistance genes (ARGs) is recognized as the most dominant dissemination pathway of ARGs in humans, animals and environmental settings. Antibiotic selective pressure has always been regarded as one of the crucial contributors to promoting the dissemination of antibiotic resistance through horizontal gene transfer (HGT). However, the roles of exogenous compounds and particularly non-antibiotic drugs in the spread of ARGs are still underappreciated. In this review, we first summarize the major pathways of HGT in bacteria, including conjugation, transformation, transduction and vesiduction. Subsequently, an overview of these compounds capable of promoting the HGT is presented, which guides to the formulation of more reasonable dosing regimens and drug residue standards in clinical practice. By contrast, these compounds that display an inhibition effect on HGT are also highlighted, which provides a unique strategy to minimize the spread of ARGs. Lastly, we discuss the implementations and challenges in bringing these HGT inhibitors into clinical trials.202032784449
401220.9999Augmented dissemination of antibiotic resistance elicited by non-antibiotic factors. The emergence and rapid spread of antibiotic resistance seriously compromise the clinical efficacy of current antibiotic therapies, representing a serious public health threat worldwide. Generally, drug-susceptible bacteria can acquire antibiotic resistance through genetic mutation or gene transfer, among which horizontal gene transfer (HGT) plays a dominant role. It is widely acknowledged that the sub-inhibitory concentrations of antibiotics are the key drivers in promoting the transmission of antibiotic resistance. However, accumulating evidence in recent years has shown that in addition to antibiotics, non-antibiotics can also accelerate the horizontal transfer of antibiotic resistance genes (ARGs). Nevertheless, the roles and potential mechanisms of non-antibiotic factors in the transmission of ARGs remain largely underestimated. In this review, we depict the four pathways of HGT and their differences, including conjugation, transformation, transduction and vesiduction. We summarize non-antibiotic factors accounting for the enhanced horizontal transfer of ARGs and their underlying molecular mechanisms. Finally, we discuss the limitations and implications of current studies.202337327521
640630.9998The Environmental Lifecycle of Antibiotics and Resistance Genes: Transmission Mechanisms, Challenges, and Control Strategies. Antibiotics are widely used in modern medicine. However, as global antibiotic consumption rises, environmental contamination with antibiotics and antibiotic resistance genes (ARGs) is becoming a serious concern. The impact of antibiotic use on human health is now under scrutiny, particularly regarding the emergence of antibiotic-resistant bacteria (ARB) in the environment. This has heightened interest in technologies for treating ARGs, highlighting the need for effective solutions. This review traces the life cycle of ARB and ARGs driven by human activity, revealing pathways from antibiotic use to human infection. We address the mechanisms enabling resistance in ARB during this process. Beyond intrinsic resistance, the primary cause of ARB resistance is the horizontal gene transfer (HGT) of ARGs. These genes exploit mobile genetic elements (MGEs) to spread via conjugation, transformation, transduction, and outer membrane vesicles (OMVs). Currently, biological wastewater treatment is the primary pollution control method due to its cost-effectiveness. However, these biological processes can promote ARG propagation, significantly amplifying the environmental threat posed by antibiotics. This review also summarizes key mechanisms in the biological treatment of antibiotics and evaluates risks associated with major ARB/ARG removal processes. Our aim is to enhance understanding of ARB risks, their pathways and mechanisms in biotreatment, and potential biomedical applications for pollution control.202541011444
963940.9998Co-selection mechanism for bacterial resistance to major chemical pollutants in the environment. Bacterial resistance is an emerging global public health problem, posing a significant threat to animal and human health. Chemical pollutants present in the environment exert selective pressure on bacteria, which acquire resistance through co-resistance, cross-resistance, co-regulation, and biofilm resistance. Resistance genes are horizontally transmitted in the environment through four mechanisms including conjugation transfer, bacterial transformation, bacteriophage transduction, and membrane vesicle transport, and even enter human bodies through the food chain, endangering human health. Although the co-selection effects of bacterial resistance to chemical pollutants has attracted widespread attention, the co-screening mechanism and co-transmission mechanisms remain unclear. Therefore, this article summarises the current research status of the co-selection effects and mechanism of environmental pollutants resistance, emphasising the necessity of studying the co-selection mechanism of bacteria against major chemical pollutants, and lays a solid theoretical foundation for conducting risk assessment of bacterial resistance.202438101638
640550.9998Extracellular DNA (eDNA): Neglected and Potential Sources of Antibiotic Resistant Genes (ARGs) in the Aquatic Environments. Over the past decades, the rising antibiotic resistance bacteria (ARB) are continuing to emerge as a global threat due to potential public health risk. Rapidly evolving antibiotic resistance and its persistence in the environment, have underpinned the need for more studies to identify the possible sources and limit the spread. In this context, not commonly studied and a neglected genetic material called extracellular DNA (eDNA) is gaining increased attention as it can be one of the significant drivers for transmission of extracellular ARGS (eARGs) via horizontal gene transfer (HGT) to competent environmental bacteria and diverse sources of antibiotic-resistance genes (ARGs) in the environment. Consequently, this review highlights the studies that address the environmental occurrence of eDNA and encoding eARGs and its impact on the environmental resistome. In this review, we also brief the recent dedicated technological advancements that are accelerating extraction of eDNA and the efficiency of treatment technologies in reducing eDNA that focuses on environmental antibiotic resistance and potential ecological health risk.202033114079
401660.9998Antimicrobial-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
401570.9998Bacteriophages 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
644680.9998Ecological consequences of antimicrobial residues and bioactive chemicals on antimicrobial resistance in agroecosystems. BACKGROUND: The widespread use of antimicrobials in agriculture, coupled with bioactive chemicals like pesticides and growth-promoting agents, has accelerated the global crisis of antimicrobial resistance (AMR). Agroecosystems provides a platform in the evolution and dissemination of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs), which pose significant threats to both environmental and public health. AIM OF REVIEW: This review explores the ecological consequences of antimicrobial residues and bioactive chemicals in agroecosystems, with a focus on their role in shaping AMR. It delves into the mechanisms by which these substances enter agricultural environments, their interactions with soil microbiomes, and the subsequent impacts on microbial community structure. KEY SCIENTIFIC CONCEPTS OF REVIEW: Evidence indicates that the accumulation of antimicrobials promotes resistance gene transfer among microorganisms, potentially compromising ecosystem health and agricultural productivity. By synthesizing current research, we identify critical gaps in knowledge and propose strategies for mitigating the ecological risks associated with antimicrobial residues. Moreover, this review highlights the urgent need for integrated management approaches to preserve ecosystem health and combat the spread of AMR in agricultural settings.202539414225
401190.9998Horizontal Gene Transfer of Antibiotic Resistance Genes in Biofilms. Most bacteria attach to biotic or abiotic surfaces and are embedded in a complex matrix which is known as biofilm. Biofilm formation is especially worrisome in clinical settings as it hinders the treatment of infections with antibiotics due to the facilitated acquisition of antibiotic resistance genes (ARGs). Environmental settings are now considered as pivotal for driving biofilm formation, biofilm-mediated antibiotic resistance development and dissemination. Several studies have demonstrated that environmental biofilms can be hotspots for the dissemination of ARGs. These genes can be encoded on mobile genetic elements (MGEs) such as conjugative and mobilizable plasmids or integrative and conjugative elements (ICEs). ARGs can be rapidly transferred through horizontal gene transfer (HGT) which has been shown to occur more frequently in biofilms than in planktonic cultures. Biofilm models are promising tools to mimic natural biofilms to study the dissemination of ARGs via HGT. This review summarizes the state-of-the-art of biofilm studies and the techniques that visualize the three main HGT mechanisms in biofilms: transformation, transduction, and conjugation.202336830238
6454100.9998Detection and various environmental factors of antibiotic resistance gene horizontal transfer. Bacterial antibiotic resistance in water environments is becoming increasingly severe, and new antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have also attracted the attention of researchers. The horizontal transfer of ARGs in water environments is considered one of the main sources of bacterial resistance in the natural environment. Horizontal gene transfer (HGT) mainly includes conjugation, natural transformation, and transduction, and conjugation has been investigated most. Several studies have shown that there are a large number of environmental factors that might affect the horizontal transfer of ARGs in water environments, such as nanomaterials, various oxidants, and light; however, there is still a lack of systematic and comprehensive reviews on the detection and the effects of the influence factors of on ARG horizontal transfer. Therefore, this study introduced three HGT modes, analysed the advantages and disadvantages of current methods for monitoring HGT, and then summarized the influence and mechanism of various factors on ARG horizontal transfer, and the possible reasons for the different effects caused by similar factors were mainly critically discussed. Finally, existing research deficiencies and future research directions of ARG horizontal transfer in water environments were discussed.202235413299
6459110.9998Aquatic systems: maintaining, mixing and mobilising antimicrobial resistance? Bacteria showing antimicrobial resistance (AMR) pose a significant global healthcare problem. Although many mechanisms conferring AMR are understood, the ecological processes facilitating its persistence and spread are less well characterised. Aquatic systems represent an important milieu for the environmental release, mixing, persistence and spread of AMR bacteria and resistance genes associated with horizontally transferable genetic elements. Additionally, owing to the use and discharge of antimicrobials and biocides, and the accumulation and abundance of other pollutants, mechanisms that confer AMR might evolve in aquatic systems. In this review, we hypothesise that aquatic systems have an important ecological and evolutionary role in driving the persistence, emergence and spread of AMR, which could have consequences when attempting to reduce its occurrence in clinical settings.201121458879
9638120.9998Response of microbial antibiotic resistance to pesticides: An emerging health threat. The spread of microbial antibiotic resistance has seriously threatened public health globally. Non-antibiotic stressors have significantly contributed to the evolution of bacterial antibiotic resistance. Although numerous studies have been conducted on the potential risk of pesticide pollution for bacterial antibiotic resistance, a systematic review of these concerns is still lacking. In the present study, we elaborate the mechanism underlying the effects of pesticides on bacterial antibiotic resistance acquisition as well as the propagation of antimicrobial resistance. Pesticide stress enhanced the acquisition of antibiotic resistance in bacteria via various mechanisms, including the activation of efflux pumps, inhibition of outer membrane pores for resistance to antibiotics, and gene mutation induction. Horizontal gene transfer is a major mechanism whereby pesticides influence the transmission of antibiotic resistance genes (ARGs) in bacteria. Pesticides promoted the conjugation transfer of ARGs by increasing cell membrane permeability and increased the proportion of bacterial mobile gene elements, which facilitate the spread of ARGs. This review can improve our understanding regarding the pesticide-induced generation and spread of ARGs and antibiotic resistant bacteria. Moreover, it can be applied to reduce the ecological risks of ARGs in the future.202235977623
6456130.9998Bacteriophages as a promising approach for the biocontrol of antibiotic resistant pathogens and the reconstruction of microbial interaction networks in wastewater treatment systems: A review. Wastewater treatment plants (WWTPs) harbor a huge diversity of antibiotic remnants and intense bacterial load, making easy the interaction among the microorganisms, which in addition to the stress caused by other gene transfer and the emergence of antimicrobial-resistant bacteria (ARB) and antimicrobial-resistance genes (ARGs). Waterborne bacterial pathogens recurrently acquire novel resistance from other species, thereby reducing our ability to inhibit and treat bacterial infections. Existing treatment methods are not able to completely eliminate ARB and ARGs, which are finally released into the aquatic environment. In this review, we further evaluate bacteriophages and their potential use in the bioaugmentation of biological wastewater treatment processes and ensure a critical overview of the current situation of knowledge about the influences of phages on the structure and function of microbial communities in WWTPs. It is hoped that this deeper knowledge will enhance and underline gaps, opportunities, and priority questions to be handled in future research.202337211119
6460140.9998Biocides as drivers of antibiotic resistance: A critical review of environmental implications and public health risks. The widespread and indiscriminate use of biocides poses significant threats to global health, socioeconomic development, and environmental sustainability by accelerating antibiotic resistance. Bacterial resistance development is highly complex and influenced significantly by environmental factors. Increased biocide usage in households, agriculture, livestock farming, industrial settings, and hospitals produces persistent chemical residues that pollute soil and aquatic environments. Such contaminants contribute to the selection and proliferation of resistant bacteria and antimicrobial resistance genes (ARGs), facilitating their dissemination among humans, animals, and ecosystems. In this review, we conduct a critical assessment of four significant issues pertaining to this topic. Specifically, (i) the role of biocides in exerting selective pressure within the environmental resistome, thereby promoting the proliferation of resistant microbial populations and contributing to the global spread of antimicrobial resistance genes (ARGs); (ii) the role of biocides in triggering transient phenotypic adaptations in bacteria, including efflux pump overexpression, membrane alterations, and reduced porin expression, which often result in cross-resistance to multiple antibiotics; (iii) the capacity of biocides to disrupt bacteria and make the genetic content accessible, releasing DNA into the environment that remains intact under certain conditions, facilitating horizontal gene transfer and the spread of resistance determinants; (iv) the capacity of biocides to disrupt bacterial cells, releasing intact DNA into the environment and enhancing horizontal gene transfer of resistance determinants; and (iv) the selective interactions between biocides and bacterial biofilms in the environment, strengthening biofilm cohesion, inducing resistance mechanisms, and creating reservoirs for resistant microorganisms and ARG dissemination. Collectively, this review highlights the critical environmental and public health implications of biocide use, emphasizing an urgent need for strategic interventions to mitigate their role in antibiotic resistance proliferation.202540230384
4094150.9998Impact 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
4014160.9998Dissemination 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
4017170.9998Non-antibiotic compounds associated with humans and the environment can promote horizontal transfer of antimicrobial resistance genes. Horizontal gene transfer plays a key role in the global dissemination of antimicrobial resistance (AMR). AMR genes are often carried on self-transmissible plasmids, which are shared amongst bacteria primarily by conjugation. Antibiotic use has been a well-established driver of the emergence and spread of AMR. However, the impact of commonly used non-antibiotic compounds and environmental pollutants on AMR spread has been largely overlooked. Recent studies found common prescription and over-the-counter drugs, artificial sweeteners, food preservatives, and environmental pollutants, can increase the conjugative transfer of AMR plasmids. The potential mechanisms by which these compounds promote plasmid transmission include increased membrane permeability, upregulation of plasmid transfer genes, formation of reactive oxygen species, and SOS response gene induction. Many questions remain around the impact of most non-antibiotic compounds on AMR plasmid conjugation in clinical isolates and the long-term impact on AMR dissemination. By elucidating the role of routinely used pharmaceuticals, food additives, and pollutants in the dissemination of AMR, action can be taken to mitigate their impact by closely monitoring use and disposal. This review will discuss recent progress on understanding the influence of non-antibiotic compounds on plasmid transmission, the mechanisms by which they promote transfer, and the level of risk they pose.202437462915
6504180.9998Antibiotic Resistance in the Drinking Water: Old and New Strategies to Remove Antibiotics, Resistant Bacteria, and Resistance Genes. Bacterial resistance is a naturally occurring process. However, bacterial antibiotic resistance has emerged as a major public health problem in recent years. The accumulation of antibiotics in the environment, including in wastewaters and drinking water, has contributed to the development of antibiotic resistant bacteria and the dissemination of antibiotic resistance genes (ARGs). Such can be justified by the growing consumption of antibiotics and their inadequate elimination. The conventional water treatments are ineffective in promoting the complete elimination of antibiotics and bacteria, mainly in removing ARGs. Therefore, ARGs can be horizontally transferred to other microorganisms within the aquatic environment, thus promoting the dissemination of antibiotic resistance. In this review, we discuss the efficiency of conventional water treatment processes in removing agents that can spread/stimulate the development of antibiotic resistance and the promising strategies for water remediation, mainly those based on nanotechnology and microalgae. Despite the potential of some of these approaches, the elimination of ARGs remains a challenge that requires further research. Moreover, the development of new processes must avoid the release of new contaminants for the environment, such as the chemicals resulting from nanomaterials synthesis, and consider the utilization of green and eco-friendly alternatives such as biogenic nanomaterials and microalgae-based technologies.202235455389
6445190.9998Microplastics: Disseminators of antibiotic resistance genes and pathogenic bacteria. Microplastics (MPs) are emerging pollutants that linger in the air, water, and land. Beyond their physical and chemical risks, there is growing evidence that MPs contribute to the worldwide antimicrobial resistance (AMR) dilemma by acting as carriers of harmful microbes and antibiotic resistance genes (ARGs). Despite an increase in research, the available literature is dispersed, and the part that MPs play in influencing microbial populations and fostering resistance is still not well understood. This review summarizes current research on how MPs contribute to the spread of antibiotic resistance. We concentrated on the ways in which MPs support horizontal gene transfer (HGT) processes such as conjugation, transformation, and transduction, assist biofilm development, and offer surfaces for microbial colonization. Evidence from a variety of settings suggests that MPs serve as vectors for opportunistic pathogens, such as the ESKAPE group, and ARGs, increasing the survival and movement of resistance determinants in ecosystems. Through the consolidation of current developments, this review emphasizes MPs as active resistance vectors instead of passive pollutants. We also point out important limitations, such as the lack of standardized procedures, inadequate risk assessment frameworks, and the absence of real-world exposure research. It is imperative that these issues be approached from a One Health standpoint in order to reduce the risks of both plastic pollution and antibiotic resistance.202541056605