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 Table of Contents  
OPINION ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 4  |  Page : 191-193

Expanding antimicrobial resistance and shrinking antibiotic arsenal: Phytochemicals—A ray of hope


1 Department of Medical Biotechnology, Mahatma Gandhi Mission Medical College and Research Institute, MGM School of Biomedical Sciences, MGM Institute of Health Sciences, Navi Mumbai, Maharashtra, India
2 Postgraduate Department and Research Centre in Biotechnology, Modern College of Arts, Science, and Commerce, Ganeshkhind, India; Department of Environmental Science, Savitribai Phule Pune University, Pune, Maharashtra, India

Date of Submission16-Mar-2020
Date of Acceptance23-Mar-2020
Date of Web Publication29-Apr-2020

Correspondence Address:
Dr. Vinay Kumar
Postgraduate Department and Research Centre in Biotechnology, Modern College of Arts, Science, and Commerce, Ganeshkhind, Pune.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mgmj.mgmj_22_20

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Keywords: Antibiotics, antimicrobial resistance, MDR, medicinal plants, PDR, phytochemicals, XDR


How to cite this article:
Thakur M, Kumar V. Expanding antimicrobial resistance and shrinking antibiotic arsenal: Phytochemicals—A ray of hope. MGM J Med Sci 2019;6:191-3

How to cite this URL:
Thakur M, Kumar V. Expanding antimicrobial resistance and shrinking antibiotic arsenal: Phytochemicals—A ray of hope. MGM J Med Sci [serial online] 2019 [cited 2020 Oct 31];6:191-3. Available from: http://www.mgmjms.com/text.asp?2019/6/4/191/283461



Recent years have witnessed an unprecedented growth both in terms of incidences and intensity of ineffectiveness of commonly available antibiotics against microbial infections, a phenomenon is known as antimicrobial resistance (AMR) or antibiotic resistance or drug resistance. The increasing levels of AMR can be categorized as the multidrug resistance (MDR), extensive drug resistance (XDR), and the pan-drug resistance (PDR), where MDR denotes the acquisition of non-susceptibility to at least one agent in three or more antimicrobial classes, and XDR indicates the non-susceptibility to at least one agent in all, except two or fewer antimicrobial classes. PDR implies non-susceptibility to all antimicrobial agents from all classes. AMR has emerged as a complicated phenomenon, leaving antibiotics or antimicrobial drugs largely ineffective. AMR has exploded in the past few years and is regarded as one of the greatest threats of the twenty-first century to human health,[1],[2],[3] placed among the top 10 urgent threats by the World Health Organization for the year 2019.[4] The severity and the scale of the problem can be illustrated by the recent commitment and advocacy by the Heads of States at the United Nations General Assembly for immediate efforts to control these microbial resistances. Recent projections are if substantial steps are not taken, then the number of deaths globally may reach a figure of 10 million per year by 2050 due to AMR infections, much more than that of cancer,[5] besides escalating the treatment costs [Figure 1].
Figure 1: Total deaths projected by 2050 attributable to antimicrobial resistance (AMR) every year compared to other major causes of death. Reproduced under the terms of the Creative Commons Attribution 4.0 International Public License.[5] Copyright 2016

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The injudicious use of antibiotics has helped AMR to spread from nosocomial setups to community environments. Often it is not only the overuse of commonly available antibiotics in health care, agriculture, and the environment sectors that is leading to AMR, but also the inappropriate antibiotic choice and consumption, inadequate doses, and non- or poor-adherence to the treatment guidelines.[6] Unfortunately, there are not many new additions to the fading antibiotic arsenal, deteriorating the situation further and leaving a serious question that are we in the post-antibiotic era? WHO, realizing the seriousness of this and bid to guide and promote research and development (R & D) of new antimicrobial drugs, published first-ever a list of drug-resistant priority pathogens that pose the highest threat to human health [Table 1].[7]
Table 1: A list of pathogens prioritized by World Health Organization. Available from: https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf

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In such a scenario, the urgent need is to find effective and long-term solutions before it gets too late. For developing new and potent ways to curb this menace, one needs to understand the complicated AMR mechanisms evolved by the microbes both intrinsic and acquired and even at times both (illustrated in [Figure 2]). The problem of AMR is fundamentally more prominent and severe in gram-negative bacteria than the gram-positive bacteria. The main reason behind this is the presence of outer membranes in gram-negative bacteria that block or check the drug influx into the bacterial cells besides increasing the drug efflux via activating their drug-efflux pumps.[2] Major molecular determinants of drug resistance and its spread include R-genes, hindrance of the target accession, porin-mediated alteration in antibiotic susceptibility, activation of efflux pumps, a mutation in the antibiotic targets, enzyme-mediated modification/inactivation of antibiotics, and formation of biofilms [Figure 2].
Figure 2: Molecular mechanisms underlying antimicrobial resistance in pathogenic microbes. Reproduced with permission.[3] Copyright 2019, Elsevier

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Curbing these microbes and the infections caused by them is a major challenge of contemporary times and requires coordinated efforts from researchers, clinical practitioners, and policymakers. This situation demands novel and effective strategies with a holistic view of combating these life-threatening pathogens. One of the best ways is the discovery of new and effective antibiotics besides reactivation of old antibiotics; however, not many new members are in sight, not even in clinical trial phases, especially against gram-negative drug-resistant strains. However, recent years have witnessed a novel and effective approach, where new nonantibiotic compounds (such as phytochemicals, natural products, and nanomaterials) are used to resensitize these microbes against the commonly used antibiotics when they are given in combination with antibiotics, known as resistance-reversal, desensitization, or synergism.[8],[9],[10],[11] These approaches are gaining momentum. Medicinal plants and their secondary metabolites or natural products are looked upon as pool for effective phytochemicals that can either show direct antimicrobial potentials or act as re-sensitizers or resistance-reversal agents. Several phytochemicals have been identified in recent years that have any of these or both potentials. However, the success rate against MDR/XDR gram-negative strains is very low, and more and more comprehensive, in-depth studies are required to identify effective antimicrobial agents against gram-negative strains, besides the translational success is not much. All this necessitates screening of medicinal plants with traditional usages against pathogenic infections, especially by the folklores, and development of effective phytochemicals as drug-leads and their further clinical trials. Further, nanomaterials especially functionalized and green-phyto-nanomaterials are also emerging as effective antimicrobials and/or the drug-carriers have also given a ray of hope against this grieving situation.[12] However, again the translational success rate needs to be improved. So overall, though we have limited success in containing drug-resistant microbes using phytomolecules and identifying novel plant-based antimicrobial drug-leads, however, recent trends should be seen as a ray of hope for developing antimicrobials in a holistic way for a long-term, effective solution to curb drug resistance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Owen L, Laird L. Synchronous application of antibiotics and essential oils: Dual mechanisms of action as a potential solution to antibiotic resistance. Crit Rev Microbiol 2018;44:414-35.  Back to cited text no. 1
    
2.
Shriram V, Khare T, Bhagwat R, Shukla R, Kumar V. Inhibiting bacterial drug efflux pumps via phyto-therapeutics to combat threatening antimicrobial resistance. Front Microbiol 2018;9: 2990.  Back to cited text no. 2
    
3.
Yu Z, Tang J, Khare T, Kumar V. The alarming antimicrobial resistance in ESKAPEE pathogens: Can essential oils come to the rescue? Fitoterapia 2020;140:104433.  Back to cited text no. 3
    
4.
World Health Organization. Ten threats to global health in 2019. Geneva, Switzerland: WHO; 2019. Available from: https://www.who.int/news-room/feature-stories/ten-threats-to-global-health-in-2019 (Last accessed on 2020 Feb 10).  Back to cited text no. 4
    
5.
O’Neill J. Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. London, UK: Wellcome Trust; 2014. p. 20. Availablefrom: https://amr-review.org/Publications.html (Last accessed on 2020 Feb 10).  Back to cited text no. 5
    
6.
Ma YX, Wang CY, Li YY, Li J, Wan QQ, Chen JH, et al. Considerations and caveats in combating ESKAPE pathogens against nosocomial infections. Adv Sci (Weinh) 2020;7:1901872.  Back to cited text no. 6
    
7.
World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed. February 2017 news release. Geneva, Switzerland: WHO; 2017. Available from: https://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed. (Last accessed on 2020 Feb 8).  Back to cited text no. 7
    
8.
Shriram V, Jahagirdar S, Latha C, Kumar V, Puranik V, Rojatkar S, et al. A potential plasmid-curing agent, 8-epidiosbulbin E acetate, from dioscorea bulbifera L. Against multidrug-resistant bacteria. Int J Antimicrob Agents 2008;32:405-10.  Back to cited text no. 8
    
9.
Shriram V, Jahagirdar S, Latha C, Kumar V, Dhakephalkar P, Rojatkar S, et al. Antibacterial & antiplasmid activities of helicteres isora L. Indian J Med Res 2010;132:94-9.  Back to cited text no. 9
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10.
Shriram V, Kumar V, Mulla J, Latha C. Curing of plasmid-mediated antibiotic resistance in multi-drug resistant human pathogens using Alpinia galangal rhizome extract. Adv Bio Tech 2013;13:1-5.  Back to cited text no. 10
    
11.
Kumar V, Shriram V, Mulla J. Antibiotic resistance reversal of multiple drug resistant bacteria using Piper longum fruit extract. J Appl Pharma Sci 2013;3:112-6.  Back to cited text no. 11
    
12.
Mapara N, Sharma M, Shriram V, Bharadwaj R, Mohite KC, Kumar V. Antimicrobial potentials of helicteres isora silver nanoparticles against extensively drug-resistant (XDR) clinical isolates of pseudomonas aeruginosa. Appl Microbiol Biotechnol 2015;99:10655-67.  Back to cited text no. 12
    


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