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668200.9991Antibiotic resistance in agriculture: Perspectives on upcoming strategies to overcome upsurge in resistance. Antibiotic resistance is a massive problem rising constantly and spreading rapidly since the past decade. The major underlying mechanism responsible for this problem is an overuse or severe misuse of antibiotics. Regardless of this emerging global threat, antibiotics are still being widely used, not only for treatment of human infections, but also to a great extent in agriculture, livestock and animal husbandry. If the current scenario persists, we might enter into a post-antibiotic era where drugs might not be able to treat even the simplest of infections. This review discusses the current status of antibiotic utilization and molecular basis of antibiotic resistance mechanisms acquired by bacteria, along with the modes of transmittance of the resultant resistant genes into human pathogens through their cycling among different ecosystems. The main focus of the article is to provide an insight into the different molecular and other strategies currently being studied worldwide for their use as an alternate to antibiotics with an overall aim to overcome or minimize the global problem of antibiotic resistance.202134841321
408010.9991Antibacterial resistance: an emerging 'zoonosis'? Antibacterial resistance is a worldwide threat, and concerns have arisen about the involvement of animal commensal and pathogenic bacteria in the maintenance and spread of resistance genes. However, beyond the facts related to the occurrence of resistant microorganisms in food, food-producing animals and companion animals and their transmission to humans, it is important to consider the vast environmental 'resistome', the selective pathways underlying the emergence of antibacterial resistance and how we can prepare answers for tomorrow.201425348154
404820.9991Mobile genetic elements in the genus Bacteroides, and their mechanism(s) of dissemination. Bacteroides spp organisms, the predominant commensal bacteria in the human gut have become increasingly resistant to many antibiotics. They are now also considered to be reservoirs of antibiotic resistance genes due to their capacity to harbor and disseminate these genes via mobile transmissible elements that occur in bewildering variety. Gene dissemination occurs within and from Bacteroides spp primarily by conjugation, the molecular mechanisms of which are still poorly understood in the genus, even though the need to prevent this dissemination is urgent. One current avenue of research is thus focused on interventions that use non-antibiotic methodologies to prevent conjugation-based DNA transfer.201122479685
666930.9991ANTIBIOTIC RESISTANT BACTERIA IN WILDLIFE: PERSPECTIVES ON TRENDS, ACQUISITION AND DISSEMINATION, DATA GAPS, AND FUTURE DIRECTIONS. The proliferation of antibiotic-resistant bacteria in the environment has potential negative economic and health consequences. Thus, previous investigations have targeted wild animals to understand the occurrence of antibiotic resistance in diverse environmental sources. In this critical review and synthesis, we summarized important concepts learned through the sampling of wildlife for antibiotic-resistant indicator bacteria. These concepts are helpful for understanding dissemination of resistance through environmental pathways and helping to guide future research efforts. Our review begins by briefly introducing antibiotic resistance as it pertains to bacteria harbored in environmental sources such as wild animals. Next, we differentiate wildlife from other animals in the context of how diverse taxa provide different information on antibiotic resistance in the environment. In the third section of our review, we identify representative research and seminal works that illustrate important associations between the occurrence of antibiotic-resistant bacteria in wildlife and anthropogenic inputs into the environment. For example, we highlight numerous investigations that support the premise that anthropogenic inputs into the environment drive the occurrence of antibiotic resistance in bacteria harbored by free-ranging wildlife. Additionally, we summarize previous research demonstrating foraging as a mechanism by which wildlife may be exposed to anthropogenic antibiotic resistance contamination in the environment. In the fourth section of our review, we summarize molecular evidence for the acquisition and dissemination of resistance among bacteria harbored by wildlife. In the fifth section, we identify what we believe to be important data gaps and potential future directions that other researchers may find useful toward the development of efficient, informative, and impactful investigations of antibiotic-resistant bacteria in wildlife. Finally, we conclude our review by highlighting the need to move from surveys that simply identify antibiotic-resistant bacteria in wildlife toward hypothesis-driven investigations that: 1) identify point sources of antibiotic resistance; 2) provide information on risk to human and animal health; 3) identify interventions that may interrupt environmentally mediated pathways of antibiotic resistance acquisition and transmission; and 4) evaluate whether management practices are leading to desirable outcomes.202031567035
669940.9991Wildlife and Antibiotic Resistance. Antibiotic resistance is a major human health problem. While health care facilities are main contributors to the emergence, evolution and spread of antibiotic resistance, other ecosystems are involved in such dissemination. Wastewater, farm animals and pets have been considered important contributors to the development of antibiotic resistance. Herein, we review the impact of wildlife in such problem. Current evidence supports that the presence of antibiotic resistance genes and/or antibiotic resistant bacteria in wild animals is a sign of anthropic pollution more than of selection of resistance. However, once antibiotic resistance is present in the wild, wildlife can contribute to its transmission across different ecosystems. Further, the finding that antibiotic resistance genes, currently causing problems at hospitals, might spread through horizontal gene transfer among the bacteria present in the microbiomes of ubiquitous animals as cockroaches, fleas or rats, supports the possibility that these organisms might be bioreactors for the horizontal transfer of antibiotic resistance genes among human pathogens. The contribution of wildlife in the spread of antibiotic resistance among different hosts and ecosystems occurs at two levels. Firstly, in the case of non-migrating animals, the transfer will take place locally; a One Health problem. Paradigmatic examples are the above mentioned animals that cohabit with humans and can be reservoirs and vehicles for antibiotic resistance dissemination. Secondly, migrating animals, such as gulls, fishes or turtles may participate in the dissemination of antibiotic resistance across different geographic areas, even between different continents, which constitutes a Global Health issue.202235646736
418450.9991The use of aminopenicillins in animals within the EU, emergence of resistance in bacteria of animal and human origin and its possible impact on animal and human health. Aminopenicillins have been widely used for decades for the treatment of various infections in animals and humans in European countries. Following this extensive use, acquired resistance has emerged among human and animal pathogens and commensal bacteria. Aminopenicillins are important first-line treatment options in both humans and animals, but are also among limited therapies for infections with enterococci and Listeria spp. in humans in some settings. Therefore, there is a need to assess the impact of the use of these antimicrobials in animals on public and animal health. The most important mechanisms of resistance to aminopenicillins are the β-lactamase enzymes. Similar resistance genes have been detected in bacteria of human and animal origin, and molecular studies suggest that transmission of resistant bacteria or resistance genes occurs between animals and humans. Due to the complexity of epidemiology and the near ubiquity of many aminopenicillin resistance determinants, the direction of transfer is difficult to ascertain, except for major zoonotic pathogens. It is therefore challenging to estimate to what extent the use of aminopenicillins in animals could create negative health consequences to humans at the population level. Based on the extent of use of aminopenicillins in humans, it seems probable that the major resistance selection pressure in human pathogens in European countries is due to human consumption. It is evident that veterinary use of these antimicrobials increases the selection pressure towards resistance in animals and loss of efficacy will at minimum jeopardize animal health and welfare.202337229552
667560.9991Genomic Insights into Bacterial Antimicrobial Resistance Transmission and Mitigation Strategies. The rapid emergence and global spread of antimicrobial resistance in recent years have raised significant concerns about the future of modern medicine. Superbugs and multidrugresistant bacteria have become endemic in many parts of the world, raising the specter of untreatable infections. The overuse and misuse of antimicrobials over the past 80 years have undoubtedly contributed to the development of antimicrobial resistance, placing immense pressure on healthcare systems worldwide. Nonetheless, the molecular mechanisms underlying antimicrobial resistance in bacteria have existed since ancient times. Some of these mechanisms and processes have served as the precursors of current resistance determinants, highlighting the ongoing arms race between bacteria and their antimicrobial adversaries. Moreover, the environment harbors many putative resistance genes, yet we cannot still predict which of these genes will emerge and manifest as pathogenic resistance phenotypes. The presence of antibiotics in natural habitats, even at sub-inhibitory concentrations, may provide selective pressures that favor the emergence of novel antimicrobial resistance apparatus and, thus, underscores the need for a comprehensive understanding of the factors driving the persistence and spread of antimicrobial resistance. As the development of antimicrobial strategies that evade resistance is urgently needed, a clear perception of these critical factors could ultimately pave the way for the design of innovative therapeutic targets.202439021167
667070.9990Ecology of antimicrobial resistance: humans, animals, food and environment. Antimicrobial resistance is a major health problem. After decades of research, numerous difficulties in tackling resistance have emerged, from the paucity of new antimicrobials to the inefficient contingency plans to reduce the use of antimicrobials; consequently, resistance to these drugs is out of control. Today we know that bacteria from the environment are often at the very origin of the acquired resistance determinants found in hospitals worldwide. Here we define the genetic components that flow from the environment to pathogenic bacteria and thereby confer a quantum increase in resistance levels, as resistance units (RU). Environmental bacteria as well as microbiomes from humans, animals, and food represent an infinite reservoir of RU, which are based on genes that have had, or not, a resistance function in their original bacterial hosts. This brief review presents our current knowledge of antimicrobial resistance and its consequences, with special focus on the importance of an ecologic perspective of antimicrobial resistance. This discipline encompasses the study of the relationships of entities and events in the framework of curing and preventing disease, a definition that takes into account both microbial ecology and antimicrobial resistance. Understanding the flux of RU throughout the diverse ecosystems is crucial to assess, prevent and eventually predict emerging scaffolds before they colonize health institutions. Collaborative horizontal research scenarios should be envisaged and involve all actors working with humans, animals, food and the environment.201223847814
409280.9990Vertical transfer of antibiotics and antibiotic resistant strains across the mother/baby axis. Antibiotic resistance is a health and socioeconomic crisis recognized as a serious threat affecting humans worldwide. Overuse of antibiotics enhances the spread of multidrug-resistant bacteria, causing drug-resistant infections which can be difficult to treat. This resistance, mostly of the acquired type, is thus a major clinical issue. Acquired resistance can occur by horizontal transfer of genes between bacteria (community settings), by vertical transmission that can occur between mother and her offspring at birth and during lactation, or spontaneously due to antibiotic exposure. While there have been multiple studies about the horizontal transfer of antibiotic-resistance genes, not many studies have been conducted to study their vertical transmission. Vertical transmission is of importance as the early bacterial colonization of infants has an impact on their health and immune programming throughout life. This review discusses some possible mechanisms of mother-to-infant transmission of antibiotics and antibiotic-resistant strains and addresses the knowledge gaps for further studies.202234172345
396290.9990Acquired antibiotic resistance among wild animals: the case of Iberian Lynx (Lynx pardinus). The selective pressure generated by the clinical misuse of antibiotics has been the major driving force leading to the emergence of antibiotic resistance among bacteria. Antibiotics or even resistant bacteria are released into the environment and contaminate the surrounding areas. Human and animal populations in contact with these sources are able to become reservoirs of these resistant organisms. Then, due to the convergence between habitats, the contact of wild animals with other animals, humans, or human sources is now more common and this leads to an increase in the exchange of resistance determinants between their microbiota. Indeed, it seems that wildlife populations living in closer proximity to humans have higher levels of antibiotic resistance. Now, the Iberian Lynx (Lynx pardinus) is a part of this issue, being suggested as natural reservoir of acquired resistant bacteria. The emerging public health concern regarding microbial resistance to antibiotics is becoming true: the bacteria are evolving and are now affecting unintentional hosts.201425220796
4081100.9990Factors promoting and limiting antimicrobial resistance in the environment - Existing knowledge gaps. The dissemination of multidrug-resistant bacteria strains and genes carrying antibiotic resistance is currently considered to be one of the most important global problem. The WHO calls for the need to contain the spread of Antimicrobial Resistance (AMR) from all possible sources. There have been many international actions grouping scientists studying this phenomenon, and quite a lot of scientific projects devoted to this problem have already been carried out. As well, so far several strategies have been developed that can inhibit the AMR spread. In this mini-review, we highlight overlooked aspects that seem to be crucial for creating a comprehensive picture of AMR, especially in the context of One Health approach.202236204635
6683110.9990Evolution and Emergence of Antibiotic Resistance in Given Ecosystems: Possible Strategies for Addressing the Challenge of Antibiotic Resistance. Antibiotics were once considered the magic bullet for all human infections. However, their success was short-lived, and today, microorganisms have become resistant to almost all known antimicrobials. The most recent decade of the 20th and the beginning of the 21st century have witnessed the emergence and spread of antibiotic resistance (ABR) in different pathogenic microorganisms worldwide. Therefore, this narrative review examined the history of antibiotics and the ecological roles of antibiotics, and their resistance. The evolution of bacterial antibiotic resistance in different environments, including aquatic and terrestrial ecosystems, and modern tools used for the identification were addressed. Finally, the review addressed the ecotoxicological impact of antibiotic-resistant bacteria and public health concerns and concluded with possible strategies for addressing the ABR challenge. The information provided in this review will enhance our understanding of ABR and its implications for human, animal, and environmental health. Understanding the environmental dimension will also strengthen the need to prevent pollution as the factors influencing ABR in this setting are more than just antibiotics but involve others like heavy metals and biocides, usually not considered when studying ABR.202236671228
4018120.9990Mobile elements, zoonotic pathogens and commensal bacteria: conduits for the delivery of resistance genes into humans, production animals and soil microbiota. Multiple antibiotic resistant pathogens represent a major clinical challenge in both human and veterinary context. It is now well-understood that the genes that encode resistance are context independent. That is, the same gene is commonly present in otherwise very disparate pathogens in both humans and production and companion animals, and among bacteria that proliferate in an agricultural context. This can be true even for pathogenic species or clonal types that are otherwise confined to a single host or ecological niche. It therefore follows that mechanisms of gene flow must exist to move genes from one part of the microbial biosphere to another. It is widely accepted that lateral (or horizontal) gene transfer (L(H)GT) drives this gene flow. LGT is relatively well-understood mechanistically but much of this knowledge is derived from a reductionist perspective. We believe that this is impeding our ability to deal with the medical ramifications of LGT. Resistance genes and the genetic scaffolds that mobilize them in multiply drug resistant bacteria of clinical significance are likely to have their origins in completely unrelated parts of the microbial biosphere. Resistance genes are increasingly polluting the microbial biosphere by contaminating environmental niches where previously they were not detected. More attention needs to be paid to the way that humans have, through the widespread application of antibiotics, selected for combinations of mobile elements that enhance the flow of resistance genes between remotely linked parts of the microbial biosphere. Attention also needs to be paid to those bacteria that link human and animal ecosystems. We argue that multiply antibiotic resistant commensal bacteria are especially important in this regard. More generally, the post genomics era offers the opportunity for understanding how resistance genes are mobilized from a one health perspective. In the long term, this holistic approach offers the best opportunity to better manage what is an enormous problem to humans both in terms of health and food security.201323641238
6711130.9990Evolution and implementation of One Health to control the dissemination of antibiotic-resistant bacteria and resistance genes: A review. Antibiotic resistance is a serious threat to humanity and its environment. Aberrant usage of antibiotics in the human, animal, and environmental sectors, as well as the dissemination of resistant bacteria and resistance genes among these sectors and globally, are all contributing factors. In humans, antibiotics are generally used to treat infections and prevent illnesses. Antibiotic usage in food-producing animals has lately emerged as a major public health concern. These medicines are currently being utilized to prevent and treat infectious diseases and also for its growth-promoting qualities. These methods have resulted in the induction and spread of antibiotic resistant infections from animals to humans. Antibiotics can be introduced into the environment from a variety of sources, including human wastes, veterinary wastes, and livestock husbandry waste. The soil has been recognized as a reservoir of ABR genes, not only because of the presence of a wide and varied range of bacteria capable of producing natural antibiotics but also for the usage of natural manure on crop fields, which may contain ABR genes or antibiotics. Fears about the human health hazards of ABR related to environmental antibiotic residues include the possible threat of modifying the human microbiota and promoting the rise and selection of resistant bacteria, and the possible danger of generating a selection pressure on the environmental microflora resulting in environmental antibiotic resistance. Because of the connectivity of these sectors, antibiotic use, antibiotic residue persistence, and the existence of antibiotic-resistant bacteria in human-animal-environment habitats are all linked to the One Health triangle. The pillars of support including rigorous ABR surveillance among different sectors individually and in combination, and at national and international level, overcoming laboratory resource challenges, and core plan and action execution should be strictly implemented to combat and contain ABR under one health approach. Implementing One Health could help to avoid the emergence and dissemination of antibiotic resistance while also promoting a healthier One World. This review aims to emphasize antibiotic resistance and its regulatory approaches from the perspective of One Health by highlighting the interconnectedness and multi-sectoral nature of the human, animal, and environmental health or ill-health facets.202236726644
4201140.9990Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection. Resistance to therapeutic antimicrobial agents is recognized as a growing problem for both human and veterinary medicine, and the need to address the issue in both of these linked domains is a current priority in public policy. Efforts to limit antimicrobial resistance (AMR) on farms have so far focused on control of the supply and use of antimicrobial drugs, plus husbandry measures to reduce infectious disease. In the United Kingdom and some other countries, substantial progress has been made recently against targets on agricultural antimicrobial drug use. However, evidence suggests that resistant pathogenic and commensal bacteria can persist and spread within and between premises despite declining or zero antimicrobial drug use. Reasons for this are likely complex and varied but may include: bacterial adaptations to ameliorate fitness costs associated with maintenance and replication of resistance genes and associated proteins, horizontal transmission of genetic resistance determinants between bacteria, physical transfer of bacteria via movement (of animals, workers, and equipment), ineffective cleaning and disinfection, and co-selection of resistance to certain drugs by use of other antimicrobials, heavy metals, or biocides. Areas of particular concern for public health include extended-spectrum cephalosporinases and fluoroquinolone resistance among Enterobacteriaceae, livestock-associated methicillin-resistant Staphylococcus aureus, and the emergence of transmissible colistin resistance. Aspects of biosecurity have repeatedly been identified as risk factors for the presence of AMR on farm premises, but there are large gaps in our understanding of the most important risk factors and the most effective interventions. The present review aims to summarize the present state of knowledge in this area, from a European perspective.201933336931
6519150.9990Understanding the Interplay between Antimicrobial Resistance, Microplastics and Xenobiotic Contaminants: A Leap towards One Health? According to the World Health Organization, the two major public health threats in the twenty-first century are antibiotic-resistant bacteria and antibiotic-resistant genes. The reason for the global prevalence and the constant increase of antibiotic-resistant bacteria is owed to the steady rise in overall antimicrobial consumption in several medical, domestic, agricultural, industrial, and veterinary applications, with consequent environmental release. These antibiotic residues may directly contaminate terrestrial and aquatic environments in which antibiotic-resistance genes are also present. Reports suggest that metal contamination is one of the main drivers of antimicrobial resistance (AMR). Moreover, the abundance of antibiotic-resistance genes is directly connected to the predominance of metal concentrations in the environment. In addition, microplastics have become a threat as emerging contaminants because of their ubiquitous presence, bio-inertness, toughness, danger to aquatic life, and human health implications. In the environment, microplastics and AMR are interconnected through biofilms, where genetic information (e.g., ARGs) is horizontally transferred between bacteria. From this perspective, we tried to summarize what is currently known on this topic and to propose a more effective One Health policy to tackle these threats.202236612363
4192160.9990Food and human gut as reservoirs of transferable antibiotic resistance encoding genes. The increase and spread of antibiotic resistance (AR) over the past decade in human pathogens has become a worldwide health concern. Recent genomic and metagenomic studies in humans, animals, in food and in the environment have led to the discovery of a huge reservoir of AR genes called the resistome that could be mobilized and transferred from these sources to human pathogens. AR is a natural phenomenon developed by bacteria to protect antibiotic-producing bacteria from their own products and also to increase their survival in highly competitive microbial environments. Although antibiotics are used extensively in humans and animals, there is also considerable usage of antibiotics in agriculture, especially in animal feeds and aquaculture. The aim of this review is to give an overview of the sources of AR and the use of antibiotics in these reservoirs as selectors for emergence of AR bacteria in humans via the food chain.201323805136
4037170.9990Heavy metal resistance in bacteria from animals. Resistance to metals and antimicrobials is a natural phenomenon that existed long before humans started to use these products for veterinary and human medicine. Bacteria carry diverse metal resistance genes, often harboured alongside antimicrobial resistance genes on plasmids or other mobile genetic elements. In this review we summarize the current knowledge about metal resistance genes in bacteria and we discuss their current use in the animal husbandry.201930502728
6680180.9990Antimicrobial 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
4070190.9990Antibiotic 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