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      Crisis averted: a world united against the menace of multiple drug-resistant superbugs -pioneering anti-AMR vaccines, RNA interference, nanomedicine, CRISPR-based antimicrobials, bacteriophage therapies, and clinical artificial intelligence strategies to safeguard global antimicrobial arsenal

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          Abstract

          The efficacy of antibiotics and other antimicrobial agents in combating bacterial infections faces a grave peril in the form of antimicrobial resistance (AMR), an exceedingly pressing global health issue. The emergence and dissemination of drug-resistant bacteria can be attributed to the rampant overuse and misuse of antibiotics, leading to dire consequences such as organ failure and sepsis. Beyond the realm of individual health, the pervasive specter of AMR casts its ominous shadow upon the economy and society at large, resulting in protracted hospital stays, elevated medical expenditures, and diminished productivity, with particularly dire consequences for vulnerable populations. It is abundantly clear that addressing this ominous threat necessitates a concerted international endeavor encompassing the optimization of antibiotic deployment, the pursuit of novel antimicrobial compounds and therapeutic strategies, the enhancement of surveillance and monitoring of resistant bacterial strains, and the assurance of universal access to efficacious treatments. In the ongoing struggle against this encroaching menace, phage-based therapies, strategically tailored to combat AMR, offer a formidable line of defense. Furthermore, an alluring pathway forward for the development of vaccines lies in the utilization of virus-like particles (VLPs), which have demonstrated their remarkable capacity to elicit a robust immune response against bacterial infections. VLP-based vaccinations, characterized by their absence of genetic material and non-infectious nature, present a markedly safer and more stable alternative to conventional immunization protocols. Encouragingly, preclinical investigations have yielded promising results in the development of VLP vaccines targeting pivotal bacteria implicated in the AMR crisis, including Salmonella, Escherichia coli, and Clostridium difficile. Notwithstanding the undeniable potential of VLP vaccines, formidable challenges persist, including the identification of suitable bacterial markers for vaccination and the formidable prospect of bacterial pathogens evolving mechanisms to thwart the immune response. Nonetheless, the prospect of VLP-based vaccines holds great promise in the relentless fight against AMR, underscoring the need for sustained research and development endeavors. In the quest to marshal more potent defenses against AMR and to pave the way for visionary innovations, cutting-edge techniques that incorporate RNA interference, nanomedicine, and the integration of artificial intelligence are currently under rigorous scrutiny.

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          Most cited references65

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          Origins and evolution of antibiotic resistance.

          Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.
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            Antibiotic 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. In this Review, Larsson and Flach discuss the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance, and they explore environmental surveillance strategies that could complement clinical surveillance systems.
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              Antimicrobial resistance: A global emerging threat to public health systems.

              Antimicrobial resistance (AMR) became in the last two decades a global threat to public health systems in the world. Since the antibiotic era, with the discovery of the first antibiotics that provided consistent health benefits to human medicine, the misuse and abuse of antimicrobials in veterinary and human medicine have accelerated the growing worldwide phenomenon of AMR. This article presents an extensive overview of the epidemiology of AMR, with a focus on the link between food producing-animals and humans and on the legal framework and policies currently implemented at the EU level and globally. The ways of responding to the AMR challenges foresee an array of measures that include: designing more effective preventive measures at farm level to reduce the use of antimicrobials; development of novel antimicrobials; strengthening of AMR surveillance system in animal and human populations; better knowledge of the ecology of resistant bacteria and resistant genes; increased awareness of stakeholders on the prudent use of antibiotics in animal productions and clinical arena; and the public health and environmental consequences of AMR. Based on the global nature of AMR and considering that bacterial resistance does not recognize barriers and can spread to people and the environment, the article ends with specific recommendations structured around a holistic approach and targeted to different stakeholders.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1374976/overviewRole: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
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                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                30 November 2023
                2023
                : 14
                : 1270018
                Affiliations
                [1] 1Clinical and Biomedical Research Center (CBRC) and Multidisciplinary Laboratories (MDL), Foundation University School of Health Sciences (FUSH), Foundation University Islamabad (FUI) , Islamabad, Pakistan
                [2] 2Regional Disease Surveillance and Response Unit Sukkur , Sukkur, Sindh, Pakistan
                [3] 3International Center of Medical Sciences Research (ICMSR) , Islamabad, Pakistan
                [4] 4Akhtar Saeed Medical and Dental College (AMDC) , Lahore, Pakistan
                [5] 5Central Park Teaching Hospital , Lahore, Pakistan
                [6] 6Office of Research, Innovation, and Commercialization (ORIC), Shaheed Zulfiqar Ali Bhutto Medical University , Islamabad, Pakistan
                [7] 7Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University , Byblos, Lebanon
                Author notes

                Edited by: Abdelaziz Elgaml, Mansoura University, Egypt

                Reviewed by: Reham M. El-Tarabili, Suez Canal University, Egypt; Marwa Ibrahim Abd El-Hamid, Zagazig University, Egypt

                *Correspondence: Umar Saeed, umarsaeed15@ 123456yahoo.com
                Article
                10.3389/fmicb.2023.1270018
                10720626
                38098671
                da8e53d6-4ee1-4784-a901-dcbca94ef8ce
                Copyright © 2023 Saeed, Insaf, Piracha, Tariq, Sohail, Abbasi, Mukhtar, Usman, Fida Rana, Gilani, Noor, Noor, Waheed, Wahid, Najmi and Fazal.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 July 2023
                : 03 November 2023
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 66, Pages: 14, Words: 12338
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Microbiology
                Review
                Custom metadata
                Antimicrobials, Resistance and Chemotherapy

                Microbiology & Virology
                antimicrobial resistance,bacterial infections,virus-like particles,phage-based therapies,vaccine development,multiple drug-resistant species,artificial intelligence

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