Genomic Insights into Bacterial Antimicrobial Resistance Transmission and Mitigation Strategies. - Related Documents




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667501.0000Genomic 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
955810.9999Antimicrobial Resistance: Enzymes, Proteins, and Computational Resources. Antimicrobial resistance (AMR) is an important health concern rooted in antibiotic misuse and overuse, resulting in drug-resistant bacteria. However, resistance to these antimicrobials developed as soon as they were administered. Several variables lead to the progression of antimicrobial resistance (AMR), making it a multifaceted challenge for healthcare systems worldwide, such as erroneous diagnosis, inappropriate prescription, incomplete treatment, and many more. Getting an in-depth idea about the mechanism underlying AMR development is essential to overcome this. This review aims to provide information on how various enzymes or proteins aid in the antimicrobial resistance mechanisms and also highlight the clinical perspective of AMR, emphasizing its growing impact on patient outcomes, and incorporate the latest recent data from the World Health Organisation (WHO), underscoring the global urgency of the AMR crisis, with specific attention to trends observed in recent years. Additionally, it is intended to provide ideas about inhibitors that can inhibit the mechanism of antibiotic resistance and also to provide an idea about numerous computational resources available that can be employed to predict genes and/or proteins and enzymes involved in various antibiotic resistance mechanisms.202540770471
667620.9999Genomic interplay in bacterial communities: implications for growth promoting practices in animal husbandry. The discovery of antibiotics heralded the start of a "Golden Age" in the history of medicine. Over the years, the use of antibiotics extended beyond medical practice into animal husbandry, aquaculture and agriculture. Now, however, we face the worldwide threat of diseases caused by pathogenic bacteria that are resistant to all existing major classes of antibiotic, reflecting the possibility of an end to the antibiotic era. The seriousness of the threat is underscored by the severely limited production of new classes of antibiotics. Evolution of bacteria resistant to multiple antibiotics results from the inherent genetic capability that bacteria have to adapt rapidly to changing environmental conditions. Consequently, under antibiotic selection pressures, bacteria have acquired resistance to all classes of antibiotics, sometimes very shortly after their introduction. Arguably, the evolution and rapid dissemination of multiple drug resistant genes en-masse across microbial pathogens is one of the most serious threats to human health. In this context, effective surveillance strategies to track the development of resistance to multiple antibiotics are vital to managing global infection control. These surveillance strategies are necessary for not only human health but also for animal health, aquaculture and plant production. Shortfalls in the present surveillance strategies need to be identified. Raising awareness of the genetic events that promote co-selection of resistance to multiple antimicrobials is an important prerequisite to the design and implementation of molecular surveillance strategies. In this review we will discuss how lateral gene transfer (LGT), driven by the use of low-dose antibiotics in animal husbandry, has likely played a significant role in the evolution of multiple drug resistance (MDR) in Gram-negative bacteria and has complicated molecular surveillance strategies adopted for predicting imminent resistance threats.201425161648
668230.9999Antibiotic 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
667740.9999Biofilm exacerbates antibiotic resistance: Is this a current oversight in antimicrobial stewardship? OBJECTIVE: To raise awareness of the role of environmental biofilm in the emergence and spread of antibiotic resistance and its consideration in antimicrobial stewardship. BACKGROUND: Antibiotic resistance is a major threat to public health. Overuse of antibiotics, increased international travel, and genetic promiscuity amongst bacteria have contributed to antibiotic resistance, and global containment efforts have so far met with limited success. Antibiotic resistance is a natural mechanism by which bacteria have adapted to environmental threats over billions of years and is caused either by genetic mutations or by horizontal gene transfer. Another ancient survival strategy involves bacteria existing within a self-produced polymeric matrix, which today is termed biofilm. Biofilm similarly enables bacterial tolerance to environmental threats, and also encourages the transfer of antibiotic resistance genes between bacterial species. This natural and ubiquitous mode of bacterial life has not been considered amongst strategies to tackle antibiotic resistance in healthcare facilities, despite its ability to significantly enhance bacterial survival and persistence, and to encourage antibiotic resistance. CONCLUSION: Biofilm must be considered synonymously with antibiotic resistance because of its proficiency in transferring resistance genes as well as its innate phenotypic tolerance to antibiotics. Although biofilm falls outside of the current definition of antimicrobial stewardship, greater awareness of the existence, ubiquity, and consequences of environmental biofilm amongst healthcare practitioners is crucial to improving hygiene practices and controlling the emergence and spread of antibiotic resistance in healthcare facilities.202033081846
667850.9999Bacteriophage Therapy to Combat Microbial Infections and Antimicrobial Resistance. Antimicrobial resistance (AMR) is a global issue; however, in lower resource settings, uncontrolled measures and uncontrolled use of antibiotics in human, animal, and agricultural practices have increased their prevalence in developing countries. Various mechanisms have been implicated to explain the AMR, like the circulation of the plasmid carrying antibiotic resistance genes (ARG), mutation in target genes (intrinsic and plasmid), overexpression of efflux pumps, underexpression of porins, etc. Various therapeutic strategies used to combat AMR exist, such as nonantibiotic approaches (vaccinations or immunotherapy, nano-derived treatments, and bacteriophage therapy), Anti-plasmid and plasmid curing approaches, combinatorial approaches (combination of antibiotics as well as a combination of two different approaches), and plant-based therapeutics. In this focused review, we have discussed the potential use of bacteriophage-based therapy to combat AMR and biofilm formation through multifaceted ways, including lysis of the drug-resistant bacteria, targeting the pili of AMR plasmids conjugation systems, and use of phage-derived lytic proteins. Phages can also be used to decontaminate surfaces in healthcare settings, prevent bacterial contamination in food (meat and dairy), and control bacterial populations in environmental settings, such as water and soil. Therefore, the bacteriophages-based approach served as a dual sword and could not only prevent the spread of infectious diseases but also manage the AMR.202540757460
408560.9999The antibiotic resistome. IMPORTANCE OF THE FIELD: Antibiotics are essential for the treatment of bacterial infections and are among our most important drugs. Resistance has emerged to all classes of antibiotics in clinical use. Antibiotic resistance has, proven inevitable and very often it emerges rapidly after the introduction of a drug into the clinic. There is, therefore, a great interest in understanding the origins, scope and evolution of antibiotic resistance. AREAS COVERED IN THIS REVIEW: The review discusses the concept of the antibiotic resistome, which is the collection of all genes that directly or indirectly contribute to antibiotic resistance. WHAT THE READER WILL GAIN: The review seeks to assemble current knowledge of the resistome concept as a means of understanding the totality of resistance and not just resistance in pathogenic bacteria. TAKE HOME MESSAGE: The concept of the antibiotic resistome provides a framework for the study and understanding of how resistance emerges and evolves. Furthermore, the study of the resistome reveals strategies that can be applied in new antibiotic discoveries.201022827799
668570.9999Fighting Antibiotic Resistance: Insights Into Human Barriers and New Opportunities: Antibiotic Resistance Constantly Rises With the Development of Human Activities. We discuss Barriers and Opportunities to Get It Under Control. The public health issue of bacterial multi-resistance to antibiotics has gained awareness among the public, researchers, and the pharmaceutical sector. Nevertheless, the spread of antimicrobial resistance has been considerably aggravated by human activities, climate change, and the subsequent increased release of antibiotics, drug-resistant bacteria, and antibiotic resistance genes in the environment. The extensive use of antibiotics for medical and veterinary purposes has not only induced increasing resistance but also other health problems, including negative effects on the patient's microbiome. Preventive strategies, new treatment modalities, and increased surveillance are progressively set up. A comprehensive approach is, however, lacking for urgently tackling this adverse situation. To address this challenge, we discussed here the main causes driving antimicrobial resistance and pollution of the environment by factors favorable to the emergence of drug resistance. We next propose some key priorities for research, prevention, surveillance, and education to supervise an effective clinical and sustainable response.202540143711
944380.9999Is Genetic Mobilization Considered When Using Bacteriophages in Antimicrobial Therapy? The emergence of multi-drug resistant bacteria has undermined our capacity to control bacterial infectious diseases. Measures needed to tackle this problem include controlling the spread of antibiotic resistance, designing new antibiotics, and encouraging the use of alternative therapies. Phage therapy seems to be a feasible alternative to antibiotics, although there are still some concerns and legal issues to overcome before it can be implemented on a large scale. Here we highlight some of those concerns, especially those related to the ability of bacteriophages to transport bacterial DNA and, in particular, antibiotic resistance genes.201729206153
407990.9999Emergence and dissemination of antibiotic resistance: a global problem. Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure.201223183460
4091100.9999Insights into novel antimicrobial compounds and antibiotic resistance genes from soil metagenomes. In recent years a major worldwide problem has arisen with regard to infectious diseases caused by resistant bacteria. Resistant pathogens are related to high mortality and also to enormous healthcare costs. In this field, cultured microorganisms have been commonly focused in attempts to isolate antibiotic resistance genes or to identify antimicrobial compounds. Although this strategy has been successful in many cases, most of the microbial diversity and related antimicrobial molecules have been completely lost. As an alternative, metagenomics has been used as a reliable approach to reveal the prospective reservoir of antimicrobial compounds and antibiotic resistance genes in the uncultured microbial community that inhabits a number of environments. In this context, this review will focus on resistance genes as well as on novel antibiotics revealed by a metagenomics approach from the soil environment. Biotechnology prospects are also discussed, opening new frontiers for antibiotic development.201425278933
4087110.9999Next-generation approaches to understand and combat the antibiotic resistome. Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.201728392565
8181120.9999Bacterial resistance to antibacterial agents: Mechanisms, control strategies, and implications for global health. The spread of bacterial drug resistance has posed a severe threat to public health globally. Here, we cover bacterial resistance to current antibacterial drugs, including traditional herbal medicines, conventional antibiotics, and antimicrobial peptides. We summarize the influence of bacterial drug resistance on global health and its economic burden while highlighting the resistance mechanisms developed by bacteria. Based on the One Health concept, we propose 4A strategies to combat bacterial resistance, including prudent Application of antibacterial agents, Administration, Assays, and Alternatives to antibiotics. Finally, we identify several opportunities and unsolved questions warranting future exploration for combating bacterial resistance, such as predicting genetic bacterial resistance through the use of more effective techniques, surveying both genetic determinants of bacterial resistance and the transmission dynamics of antibiotic resistance genes (ARGs).202336435256
6684130.9999An African perspective on the prevalence, fate and effects of carbapenem resistance genes in hospital effluents and wastewater treatment plant (WWTP) final effluents: A critical review. This article provides an overview of the antibiotic era and discovery of earliest antibiotics until the present day state of affairs, coupled with the emergence of carbapenem-resistant bacteria. The ways of response to challenges of antibiotic resistance (AR) such as the development of novel strategies in the search of new antibiotics, designing more effective preventive measures as well as the ecology of AR have been discussed. The applications of plant extract and chemical compounds like nanomaterials which are based on recent developments in the field of antimicrobials, antimicrobial resistance (AMR), and chemotherapy were briefly discussed. The agencies responsible for environmental protection have a role to play in dealing with the climate crisis which poses an existential threat to the planet, and contributes to ecological support towards pathogenic microorganisms. The environment serves as a reservoir and also a vehicle for transmission of antimicrobial resistance genes hence, as dominant inhabitants we have to gain a competitive advantage in the battle against AMR.202032420480
9576140.9999Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century. With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.202134940513
6681150.9999Antimicrobial Resistance and Current Alternatives in Veterinary Practice: A Review. Antibiotics are commonly used to treat bacterial infections. For many years, antibiotics have been used at sub-therapeutic doses to promote animal growth and misused as prophylactics and metaphylactic on farms. The widespread and improper use of antibiotics has resulted in a serious problem, defined as antibiotic resistance by the World Health Organisation, which is a major public health threat in the 21st century. Bacteria have evolved sophisticated mechanistic strategies to avoid being killed by antibiotics. These strategies can be classified as intrinsic resistance (referring to the inherent structural or functional characteristics of a bacterial species) or acquired resistance (referring to mutations in chromosomal genes or the acquisition of external genetic determinants of resistance). In farm animals, the use of antibiotics warrants serious consideration, as their residues leach into the environment through effluents and come into contact with humans through food. Several factors have contributed to the emergence of antibiotic-resistant bacteria. This review provides an update on antibiotic resistance mechanisms, while focusing on the effects of this threat on veterinary medicine, and highlighting causal factors in clinical practice. Finally, it makes an excursus on alternative therapies, such as the use of bacteriophages, bacteriocins, antimicrobial photodynamic therapy, phytochemicals, and ozone therapy, which should be used to combat antibiotic-resistant infections. Some of these therapies, such as ozone therapy, are aimed at preventing the persistence of antibiotics in animal tissues and their contact with the final consumer of food of animal origin.202336717996
4016160.9999Antimicrobial-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
4245170.9999Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence. In recent years, we have seen antimicrobial resistance rapidly emerge at a global scale and spread from one country to the other faster than previously thought. Superbugs and multidrug-resistant bacteria are endemic in many parts of the world. There is no question that the widespread use, overuse, and misuse of antimicrobials during the last 80 years have been associated with the explosion of antimicrobial resistance. On the other hand, the molecular pathways behind the emergence of antimicrobial resistance in bacteria were present since ancient times. Some of these mechanisms are the ancestors of current resistance determinants. Evidently, there are plenty of putative resistance genes in the environment, however, we cannot yet predict which ones would be able to be expressed as phenotypes in pathogenic bacteria and cause clinical disease. In addition, in the presence of inhibitory and sub-inhibitory concentrations of antibiotics in natural habitats, one could assume that novel resistance mechanisms will arise against antimicrobial compounds. This review presents an overview of antimicrobial resistance mechanisms, and describes how these have evolved and how they continue to emerge. As antimicrobial strategies able to bypass the development of resistance are urgently needed, a better understanding of the critical factors that contribute to the persistence and spread of antimicrobial resistance may yield innovative perspectives on the design of such new therapeutic targets.202031659373
8182180.9999Antibiotics in Food Chain: The Consequences for Antibiotic Resistance. Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.202033066005
4067190.9999Metal 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