Multitarget Approaches against Multiresistant Superbugs
Review article, 2020

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.

antibiotic combination therapy

polypharmacology

synergy

multifunctional antibiotic

multiresistant bacteria

Author

Declan Alan Gray

Newcastle University

Michaela Wenzel

Chalmers, Biology and Biological Engineering, Chemical Biology

ACS Infectious Diseases

2373-8227 (eISSN)

Vol. 6 6 1346-1365

Antibiotic-induced amino acid release - A new antimicrobial strategy?

Swedish Research Council (VR) (2019-04521), 2020-01-01 -- 2023-12-31.

Subject Categories

Pharmaceutical Sciences

Infectious Medicine

Microbiology in the medical area

DOI

10.1021/acsinfecdis.0c00001

PubMed

32156116

More information

Latest update

10/13/2020