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      Escaping mechanisms of ESKAPE pathogens from antibiotics and their targeting by natural compounds

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          Highlights

          • ESKAPE pathogens display multidrug resistance (MDR) through various mechanisms.

          • Mechanisms adapted by ESKAPE pathogens to counteract antibiotics have been described.

          • Selected natural compounds with bactericidal effect towards ESKAPE pathogens have been listed.

          Abstract

          The microorganisms that have developed resistance to available therapeutic agents are threatening the globe and multidrug resistance among the bacterial pathogens is becoming a major concern of public health worldwide. Bacteria develop protective mechanisms to counteract the deleterious effects of antibiotics, which may eventually result in loss of growth-inhibitory potential of antibiotics. ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens display multidrug resistance and virulence through various mechanisms and it is the need of the hour to discover or design new antibiotics against ESKAPE pathogens. In this article, we have discussed the mechanisms acquired by ESKAPE pathogens to counteract the effect of antibiotics and elaborated on recently discovered secondary metabolites derived from bacteria and plant sources that are endowed with good antibacterial activity towards pathogenic bacteria in general, ESKAPE organisms in particular. Abyssomicin C, allicin, anthracimycin, berberine, biochanin A, caffeic acid, daptomycin, kibdelomycin, piperine, platensimycin, plazomicin, taxifolin, teixobactin, and thymol are the major metabolites whose antibacterial potential have been discussed in this article.

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          Most cited references239

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          Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

          The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.
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            Drugs for bad bugs: confronting the challenges of antibacterial discovery.

            The sequencing of the first complete bacterial genome in 1995 heralded a new era of hope for antibacterial drug discoverers, who now had the tools to search entire genomes for new antibacterial targets. Several companies, including GlaxoSmithKline, moved back into the antibacterials area and embraced a genomics-derived, target-based approach to screen for new classes of drugs with novel modes of action. Here, we share our experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years, and look at what we learned and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
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              Mechanisms of Antibiotic Resistance.

              Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic "attack" is the prime example of bacterial adaptation and the pinnacle of evolution. "Survival of the fittest" is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.
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                Author and article information

                Contributors
                Journal
                Biotechnol Rep (Amst)
                Biotechnol Rep (Amst)
                Biotechnology Reports
                Elsevier
                2215-017X
                04 April 2022
                June 2022
                04 April 2022
                : 34
                : e00728
                Affiliations
                [a ]Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore 570006, India
                [b ]Dayananda Sagar University, School of Basic and Applied Sciences, Shavige Malleswara Hills, Kumaraswamy layout, Bengaluru 560111, India
                [c ]Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore 570006, India
                [d ]Institution of Excellence, Vijnana Bhavan, University of Mysore, Manasagangotri, Mysore 570006, India
                Author notes
                [1]

                These authors contributed equally to this work.

                Article
                S2215-017X(22)00027-3 e00728
                10.1016/j.btre.2022.e00728
                9171455
                c5f281f6-e47f-46bc-ace0-513932892e58
                © 2022 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 31 December 2021
                : 10 March 2022
                : 31 March 2022
                Categories
                Research Article

                eskape,multidrug resistance,natural compounds,secondary metabolites

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