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Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of

Hannah E Caraway1, Jonathan Z Lau1, Bar Maron2

  • 1Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.

Antibiotics (Basel, Switzerland)
|March 25, 2022
PubMed

Insights

Random peptide mixtures (RPMs) show promise as a novel therapeutic against antibiotic-resistant Acinetobacter baumannii. These diverse peptide mixtures effectively kill bacteria, prevent biofilm formation, and improve survival in preclinical models.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Antibiotic resistance is a major global health crisis, with carbapenem-resistant Acinetobacter baumannii posing a significant threat.
  • The overuse and overreliance on existing antibiotics contribute to the rise of resistant bacterial strains.
  • New therapeutic strategies are urgently needed to combat infections caused by antibiotic-resistant pathogens.

Purpose of the Study:

  • To evaluate the efficacy of random peptide mixtures (RPMs) as an alternative therapeutic agent against Acinetobacter baumannii.
  • To investigate the potential of RPMs to overcome antibiotic resistance and prevent bacterial evolution of resistance.
  • To assess the in vivo performance of RPMs in preclinical models of infection.

Main Methods:

  • RPMs were synthesized with defined composition, chain length, and stereochemistry, ensuring extreme diversity.
  • In vitro assays were performed to assess the bactericidal activity of RPMs against various Acinetobacter baumannii strains and their ability to inhibit and disrupt biofilms.
  • In vivo studies utilized mouse models of acute pneumonia, soft tissue infection, and sepsis to evaluate RPMs' therapeutic potential and survival rates.

Main Results:

  • RPMs demonstrated rapid and efficient killing of diverse Acinetobacter baumannii strains, including carbapenem-resistant isolates.
  • RPMs effectively inhibited the formation of bacterial biofilms and disrupted pre-existing mature biofilms.
  • In vivo studies showed that RPMs attenuated bacterial burden in pneumonia and soft tissue infection models and significantly reduced mortality in a sepsis model.

Conclusions:

  • Random peptide mixtures represent a promising new class of therapeutics with potential against antibiotic-resistant Acinetobacter baumannii.
  • The inherent diversity of RPMs may hinder the rapid evolution of bacterial resistance.
  • RPMs exhibit favorable safety and pharmacokinetic profiles, positioning them as a viable alternative to conventional antibiotics.
Keywords:
Acinetobacter baumanniiacute pneumoniaantibiotic resistancebiofilmsrandom peptide mixturessepsissoft tissue infection

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