Autoinducer analogs can provide bactericidal activity to macrolides in pseudomonas aeruginosa through antibiotic tolerance reduction

Mizuki Abe, Keiji Murakami, Yuka Hiroshima, Takashi Amoh, Mayu Sebe, Keiko Kataoka, Hideki Fujii

Research output: Contribution to journalArticlepeer-review

Abstract

Macrolide antibiotics are used in treating Pseudomonas aeruginosa 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 P. aeruginosa quorum-sensing autoinducer analogs (AIA-1,-2) on the activity of azithromycin and clarithromycin against P. aeruginosa. In the killing assay of planktonic cells, AIA-1 and-2 enhanced the bactericidal ability of macrolides against P. aeruginosa 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 P. aeruginosa biofilm infections.

Original languageEnglish
Article number10
JournalAntibiotics
Volume11
Issue number1
DOIs
Publication statusPublished - 2022 Jan
Externally publishedYes

Keywords

  • Antibiotic tolerance
  • Autoinducer analog
  • Macrolide
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Microbiology
  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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