Inhibiting Bacterial Drug Efflux Pumps via Phyto-Therapeutics to Combat Threatening Antimicrobial Resistance

Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment opt...

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Published inFrontiers in microbiology Vol. 9; p. 2990
Main Authors Shriram, Varsha, Khare, Tushar, Bhagwat, Rohit, Shukla, Ravi, Kumar, Vinay
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 10.12.2018
Subjects
antimicrobial resistance
drug resistance reversal
efflux pump inhibitors
efflux pumps
Microbiology
phyto-therapeutics
drug resistance reversal
phyto-therapeutics
antimicrobial resistance
efflux pumps
efflux pump inhibitors
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Abstract Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment options and escalating mortality-rates and treatment costs. The problem is further aggravated by the drying-pipeline of new and potent antibiotics effective particularly against the drug-resistant strains. Multidrug efflux pumps (EPs) are established as principal determinants of AMR, extruding multiple antibiotics out of the cell, mostly in non-specific manner and have therefore emerged as potent drug-targets for combating AMR. Plants being the reservoir of bioactive compounds can serve as a source of potent EP inhibitors (EPIs). The phyto-therapeutics with noteworthy drug-resistance-reversal or re-sensitizing activities may prove significant for reviving the otherwise fading antibiotics arsenal and making this combination-therapy effective. Contemporary attempts to potentiate the antibiotics with plant extracts and pure phytomolecules have gained momentum though with relatively less success against Gram-negative bacteria. Plant-based EPIs hold promise as potent drug-leads to combat the EPI-mediated AMR. This review presents an account of major bacterial multidrug EPs, their roles in imparting AMR, effective strategies for inhibiting drug EPs with phytomolecules, and current account of research on developing novel and potent plant-based EPIs for reversing their AMR characteristics. Recent developments including emergence of tools, major success stories, challenges and future prospects are also discussed.
AbstractList Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment options and escalating mortality-rates and treatment costs. The problem is further aggravated by the drying-pipeline of new and potent antibiotics effective particularly against the drug-resistant strains. Multidrug efflux pumps (EPs) are established as principal determinants of AMR, extruding multiple antibiotics out of the cell, mostly in non-specific manner and have therefore emerged as potent drug-targets for combating AMR. Plants being the reservoir of bioactive compounds can serve as a source of potent EP inhibitors (EPIs). The phyto-therapeutics with noteworthy drug-resistance-reversal or re-sensitizing activities may prove significant for reviving the otherwise fading antibiotics arsenal and making this combination-therapy effective. Contemporary attempts to potentiate the antibiotics with plant extracts and pure phytomolecules have gained momentum though with relatively less success against Gram-negative bacteria. Plant-based EPIs hold promise as potent drug-leads to combat the EPI-mediated AMR. This review presents an account of major bacterial multidrug EPs, their roles in imparting AMR, effective strategies for inhibiting drug EPs with phytomolecules, and current account of research on developing novel and potent plant-based EPIs for reversing their AMR characteristics. Recent developments including emergence of tools, major success stories, challenges and future prospects are also discussed.
Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment options and escalating mortality-rates and treatment costs. The problem is further aggravated by the drying-pipeline of new and potent antibiotics effective particularly against the drug-resistant strains. Multidrug efflux pumps (EPs) are established as principal determinants of AMR, extruding multiple antibiotics out of the cell, mostly in non-specific manner and have therefore emerged as potent drug-targets for combating AMR. Plants being the reservoir of bioactive compounds can serve as a source of potent EP inhibitors (EPIs). The phyto-therapeutics with noteworthy drug-resistance-reversal or re-sensitizing activities may prove significant for reviving the otherwise fading antibiotics arsenal and making this combination-therapy effective. Contemporary attempts to potentiate the antibiotics with plant extracts and pure phytomolecules have gained momentum though with relatively less success against Gram-negative bacteria. Plant-based EPIs hold promise as potent drug-leads to combat the EPI-mediated AMR. This review presents an account of major bacterial multidrug EPs, their roles in imparting AMR, effective strategies for inhibiting drug EPs with phytomolecules, and current account of research on developing novel and potent plant-based EPIs for reversing their AMR characteristics. Recent developments including emergence of in silico tools, major success stories, challenges and future prospects are also discussed.
Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment options and escalating mortality-rates and treatment costs. The problem is further aggravated by the drying-pipeline of new and potent antibiotics effective particularly against the drug-resistant strains. Multidrug efflux pumps (EPs) are established as principal determinants of AMR, extruding multiple antibiotics out of the cell, mostly in non-specific manner and have therefore emerged as potent drug-targets for combating AMR. Plants being the reservoir of bioactive compounds can serve as a source of potent EP inhibitors (EPIs). The phyto-therapeutics with noteworthy drug-resistance-reversal or re-sensitizing activities may prove significant for reviving the otherwise fading antibiotics arsenal and making this combination-therapy effective. Contemporary attempts to potentiate the antibiotics with plant extracts and pure phytomolecules have gained momentum though with relatively less success against Gram-negative bacteria. Plant-based EPIs hold promise as potent drug-leads to combat the EPI-mediated AMR. This review presents an account of major bacterial multidrug EPs, their roles in imparting AMR, effective strategies for inhibiting drug EPs with phytomolecules, and current account of research on developing novel and potent plant-based EPIs for reversing their AMR characteristics. Recent developments including emergence of in silico tools, major success stories, challenges and future prospects are also discussed.
Author Khare, Tushar
Shukla, Ravi
Shriram, Varsha
Bhagwat, Rohit
Kumar, Vinay
AuthorAffiliation 2 Department of Biotechnology, Modern College of Arts, Science and Commerce (Savitribai Phule Pune University) , Pune , India
4 Centre for Advanced Materials and Industrial Chemistry, School of Science, RMIT University , Melbourne, VIC , Australia
1 Department of Botany, Prof. Ramkrishna More College, Savitribai Phule Pune University , Pune , India
3 Department of Environmental Science, Savitribai Phule Pune University , Pune , India
AuthorAffiliation_xml – name: 3 Department of Environmental Science, Savitribai Phule Pune University , Pune , India
– name: 2 Department of Biotechnology, Modern College of Arts, Science and Commerce (Savitribai Phule Pune University) , Pune , India
– name: 1 Department of Botany, Prof. Ramkrishna More College, Savitribai Phule Pune University , Pune , India
– name: 4 Centre for Advanced Materials and Industrial Chemistry, School of Science, RMIT University , Melbourne, VIC , Australia
Author_xml – sequence: 1
  givenname: Varsha
  surname: Shriram
  fullname: Shriram, Varsha
  organization: Department of Botany, Prof. Ramkrishna More College, Savitribai Phule Pune University, Pune, India
– sequence: 2
  givenname: Tushar
  surname: Khare
  fullname: Khare, Tushar
  organization: Department of Biotechnology, Modern College of Arts, Science and Commerce (Savitribai Phule Pune University), Pune, India
– sequence: 3
  givenname: Rohit
  surname: Bhagwat
  fullname: Bhagwat, Rohit
  organization: Department of Environmental Science, Savitribai Phule Pune University, Pune, India
– sequence: 4
  givenname: Ravi
  surname: Shukla
  fullname: Shukla, Ravi
  organization: Centre for Advanced Materials and Industrial Chemistry, School of Science, RMIT University, Melbourne, VIC, Australia
– sequence: 5
  givenname: Vinay
  surname: Kumar
  fullname: Kumar, Vinay
  organization: Department of Environmental Science, Savitribai Phule Pune University, Pune, India
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30619113$$D View this record in MEDLINE/PubMed
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Copyright Copyright © 2018 Shriram, Khare, Bhagwat, Shukla and Kumar. 2018 Shriram, Khare, Bhagwat, Shukla and Kumar
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Keywords drug resistance reversal
phyto-therapeutics
antimicrobial resistance
efflux pumps
efflux pump inhibitors
Language English
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This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology
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PublicationTitle Frontiers in microbiology
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SecondaryResourceType review_article
Snippet Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance...
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StartPage 2990
SubjectTerms antimicrobial resistance
drug resistance reversal
efflux pump inhibitors
efflux pumps
Microbiology
phyto-therapeutics
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Title Inhibiting Bacterial Drug Efflux Pumps via Phyto-Therapeutics to Combat Threatening Antimicrobial Resistance
URI https://www.ncbi.nlm.nih.gov/pubmed/30619113
https://search.proquest.com/docview/2165042999
https://pubmed.ncbi.nlm.nih.gov/PMC6295477
https://doaj.org/article/7b6e79664cce47e7a3be0e5d7c238912
Volume 9
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