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Multitarget Approaches against Multiresistant Superbugs

Authors
  • Gray, Declan Alan1
  • Wenzel, Michaela2
  • 1 Newcastle University, United Kingdom , (United Kingdom)
  • 2 Chalmers University of Technology, Sweden , (Sweden)
Type
Published Article
Journal
ACS Infectious Diseases
Publisher
American Chemical Society
Publication Date
Mar 10, 2020
Volume
6
Issue
6
Pages
1346–1365
Identifiers
DOI: 10.1021/acsinfecdis.0c00001
PMID: 32156116
PMCID: PMC7307902
Source
PubMed Central
Keywords
Disciplines
  • Review
License
Unknown

Abstract

Despite efforts to develop new antibiotics, antibacterial resistance still develops too fast for drug discovery to keep pace. Often, resistance against a new drug develops even before it reaches the market. This continued resistance crisis has demonstrated that resistance to antibiotics with single protein targets develops too rapidly to be sustainable. Most successful long-established antibiotics target more than one molecule or possess targets, which are encoded by multiple genes. This realization has motivated a change in antibiotic development toward drug candidates with multiple targets. Some mechanisms of action presuppose multiple targets or at least multiple effects, such as targeting the cytoplasmic membrane or the carrier molecule bactoprenol phosphate and are therefore particularly promising. Moreover, combination therapy approaches are being developed to break antibiotic resistance or to sensitize bacteria to antibiotic action. In this Review, we provide an overview of antibacterial multitarget approaches and the mechanisms behind them.

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