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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
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Going Beyond Host Defence Peptides: Horizons of Chemically Engineered Peptides for Multidrug-Resistant Bacteria

Bernardo Cavallazzi Sebold1,2, Junjie Li3, Guoying Ni1,3,4

  • 1Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
|June 10, 2023
PubMed

Insights

Multidrug-resistant bacteria pose a global threat. Chemical engineering of host defence peptides (HDPs) shows promise in improving their effectiveness against challenging pathogens like the ESKAPE group.

Area of Science:

  • Microbiology
  • Biochemistry
  • Medicinal Chemistry

Background:

  • Multidrug-resistant (MDR) bacteria, particularly the ESKAPE pathogens, represent a significant and growing global health concern.
  • Host defence peptides (HDPs) exhibit antimicrobial activity against MDR bacteria, including within biofilms.
  • The clinical application of HDPs is limited by poor pharmacokinetics in physiological environments.

Purpose of the Study:

  • To review chemical modifications of HDPs aimed at enhancing their pharmacokinetic properties and antimicrobial efficacy.
  • To highlight promising modifications effective against ESKAPE pathogens.

Main Methods:

  • Literature review of studies involving chemically modified HDPs.
  • Analysis of modifications targeting improved pharmacokinetics and antimicrobial activity.
  • Focus on efficacy against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens).

Main Results:

  • Various chemical modifications have successfully improved HDP pharmacokinetics.
  • Modified HDPs demonstrate enhanced efficacy against ESKAPE pathogens in vitro and in vivo.
  • Specific modifications offer strategies to overcome limitations of native HDPs.

Conclusions:

  • Chemical engineering is a viable strategy to develop HDPs into effective clinical agents against MDR infections.
  • Modified HDPs hold significant potential for combating the threat posed by ESKAPE pathogens.
  • Further research into HDP modification is crucial for advancing antimicrobial therapies.

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