Autoinducer Analogs Can Provide Bactericidal Activity to Macrolides in Through Antibiotic Tolerance Reduction

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2022 Jan 21

PMID 35052885

Authors

Mizuki Abe

Keiji Murakami

Yuka Hiroshima

Takashi Amoh

Mayu Sebe

Keiko Kataoka

Hideki Fujii

Affiliations

Soon will be listed here.

Abstract

Macrolide antibiotics are used in treating chronic biofilm infections despite their unsatisfactory antibacterial activity, because they display several special activities, such as modulation of the bacterial quorum sensing and immunomodulatory effects on the host. In this study, we investigated the effects of the newly synthesized quorum-sensing autoinducer analogs (AIA-1, -2) on the activity of azithromycin and clarithromycin against . In the killing assay of planktonic cells, AIA-1 and -2 enhanced the bactericidal ability of macrolides against PAO1; however, they did not affect the minimum inhibitory concentrations of macrolides. In addition, AIA-1 and -2 considerably improved the killing activity of azithromycin and clarithromycin in biofilm cells. The results indicated that AIA-1 and -2 could affect antibiotic tolerance. Moreover, the results of hydrocarbon adherence and cell membrane permeability assays suggested that AIA-1 and -2 changed bacterial cell surface hydrophobicity and accelerated the outer membrane permeability of the hydrophobic antibiotics such as azithromycin and clarithromycin. Our study demonstrated that the new combination therapy of macrolides and AIA-1 and -2 may improve the therapeutic efficacy of macrolides in the treatment of chronic biofilm infections.

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