Strategies against methicillin-resistant Staphylococcus aureus persisters

Future Med Chem. 2018 Apr 1;10(7):779-794. doi: 10.4155/fmc-2017-0199. Epub 2018 Mar 23.

Abstract

Chronic Staphylococcus aureus infections are complicated by frequent relapses not only from the development of drug resistance to conventional antibiotics, but also through the formation of persister bacterial cells. Bacterial persisters are in a transient, metabolically inactive state, making conventional antibiotics that target essential cellular growth processes ineffective, resulting in high clinical failure rates of antibiotic chemotherapy. The development of new antibiotics against persistent S. aureus is an urgent issue. Over the last decade, new strategies to identify S. aureus persister-active compounds have been proposed. This review summarizes the proposed targets, antipersister compounds and innovative methods that may augment conventional antibiotics against S. aureus persisters. The reviewed antipersister strategies can be summarized as two broad categories; directly targeting growth-independent targets and potentiating existing, ineffective antibiotics by aiding uptake or accessibility.

Keywords: MRSA; antibiotics; drug discover; persisters.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Cell Membrane Permeability / drug effects
  • Disease Models, Animal
  • Drug Approval / legislation & jurisprudence
  • Drug Discovery
  • Drug Repositioning
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Peptide Hydrolases / metabolism
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology*
  • United States
  • United States Food and Drug Administration

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Bacterial Proteins
  • Peptide Hydrolases