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Autoinducer Analogs Can Provide Bactericidal Activity to Macrolides in Pseudomonas aeruginosa through Antibiotic

Mizuki Abe1,2, Keiji Murakami1,3, Yuka Hiroshima1

  • 1Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan.

Antibiotics (Basel, Switzerland)
|January 21, 2022
PubMed

Insights

Newly synthesized quorum-sensing analogs (AIA-1, -2) enhance macrolide antibiotic effectiveness against Pseudomonas aeruginosa biofilms. This combination therapy shows promise for treating chronic biofilm infections by improving bacterial killing and antibiotic tolerance.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Macrolide antibiotics are used for chronic *Pseudomonas aeruginosa* biofilm infections, but their efficacy is limited.
  • Macrolides possess quorum sensing modulation and immunomodulatory effects beneficial in treating these infections.

Purpose of the Study:

  • To investigate the impact of novel *P. aeruginosa* quorum-sensing autoinducer analogs (AIA-1, -2) on macrolide activity.
  • To evaluate the combined effects of AIA-1, -2 with azithromycin and clarithromycin against *P. aeruginosa*.

Main Methods:

  • Killing assays were performed on planktonic and biofilm cells of *P. aeruginosa*.
  • Minimum inhibitory concentrations (MICs) of macrolides were assessed.
  • Hydrocarbon adherence and cell membrane permeability assays were conducted.

Main Results:

  • AIA-1 and -2 enhanced macrolide bactericidal activity against planktonic cells but did not alter MICs.
  • Significant improvement in macrolide killing activity was observed in biofilm cells.
  • AIA-1 and -2 altered bacterial cell surface hydrophobicity and increased outer membrane permeability.

Conclusions:

  • AIA-1 and -2 enhance the efficacy of macrolides against *P. aeruginosa* biofilms.
  • The combination of macrolides with AIA-1 and -2 may offer improved therapeutic outcomes for chronic biofilm infections.
  • These analogs show potential in overcoming antibiotic tolerance in *P. aeruginosa*.
Keywords:
Pseudomonas aeruginosaantibiotic toleranceautoinducer analogmacrolide

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