Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics.

Content Provider	Europe PMC
Author	Wesseling, CharlotteM. J. Martin, Nathaniel I.
Copyright Year	2022
Abstract	New approaches to target antibacterial agents towardGram-negativebacteria are key, given the rise of antibiotic resistance. Since thediscovery of polymyxin B nonapeptide as a potent Gram-negativeouter membrane (OM)-permeabilizing synergist in the early 1980s, avast amount of literature on such synergists has been published. ThisReview addresses a range of peptide-based and small organic compoundsthat disrupt the OM to elicit a synergistic effect with antibioticsthat are otherwise inactive toward Gram-negative bacteria, with synergydefined as a fractional inhibitory concentration index (FICI) of <0.5.Another requirement for the inclusion of the synergists here coveredis their potentiation of a specific set of clinically used antibiotics:erythromycin, rifampicin, novobiocin, or vancomycin. In addition,we have focused on those synergists with reported activity againstGram-negative members of the ESKAPE family of pathogens namely, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and/or Acinetobacterbaumannii. In cases where the FICI values were not directlyreported in the primary literature but could be calculated from thepublished data, we have done so, allowing for more direct comparisonof potency with other synergists. We also address the hemolytic activityof the various OM-disrupting synergists reported in the literature,an effect that is often downplayed but is of key importance in assessingthe selectivity of such compounds for Gram-negative bacteria.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9469101&blobtype=pdf
Journal	ACS Infectious Diseases [ACS Infect Dis]
Volume Number	8
DOI	10.1021/acsinfecdis.2c00193
PubMed Central reference number	PMC9469101
Issue Number	9
PubMed reference number	35946799
e-ISSN	23738227
Language	English
Publisher	American Chemical Society
Publisher Date	2022-08-10
Access Restriction	Open
Rights License	Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). © 2022 The Authors. Published by American Chemical Society
Subject Keyword	Gram-negative bacteria Gram-positive antibiotics synergy outer membrane permeabilization potentiators
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases