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A Novel Truncated CHAP Modular Endolysin, CHAPSAP26-161, That Lyses Staphylococcus aureus, Acinetobacter baumannii,

Yoon-Jung Choi1, Shukho Kim1, Ram Hari Dahal1

  • 1Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.

Journal of Microbiology and Biotechnology
|July 31, 2024
PubMed

Insights

A novel truncated endolysin, CHAPSAP26-161, shows enhanced antibacterial activity against multidrug-resistant bacteria like A. baumannii and S. aureus. In vivo studies confirm its therapeutic potential as a new antibacterial agent.

Area of Science:

  • Microbiology and Molecular Biology
  • Drug Discovery and Development

Background:

  • Antibiotic resistance poses a significant global health threat, necessitating the development of novel antibacterial agents.
  • Endolysins, bacteriophage-derived enzymes, are promising candidates due to their specific lytic activity and novel mechanisms of action.

Purpose of the Study:

  • To develop and evaluate a novel truncated endolysin, CHAPSAP26-161, derived from LysSAP26.
  • To assess its enhanced antibacterial activity, protein purification efficiency, and in vivo efficacy against multidrug-resistant (MDR) bacteria.

Main Methods:

  • Expression and purification of CHAPSAP26-161 in E. coli.
  • In vitro assessment of lytic activity against MDR strains including Acinetobacter baumannii, Staphylococcus aureus, and Clostridioides difficile.
  • Evaluation of enzyme stability across a range of pH and temperatures, and the effect of Zn2+ on lytic activity.
  • In vivo efficacy testing in a murine model of systemic A. baumannii infection.

Main Results:

  • CHAPSAP26-161 demonstrated superior protein purification efficiency and antibacterial activity compared to the parent LysSAP26.
  • High lytic activity was observed against A. baumannii (MBCs 5-10 μg/ml) and S. aureus (MBCs 10-25 μg/ml), and also against anaerobic C. difficile (MBCs 25-50 μg/ml).
  • CHAPSAP26-161 maintained activity across pH 4-8 and temperatures of 4°C-45°C, with enhanced activity in the presence of Zn2+.
  • Significant therapeutic effects were observed in vivo in a murine model of A. baumannii infection.

Conclusions:

  • The truncated endolysin CHAPSAP26-161 exhibits enhanced properties and broad-spectrum antibacterial activity against key MDR pathogens.
  • Its stability and efficacy in vitro and in vivo highlight its potential as an innovative therapeutic agent against antibiotic-resistant bacteria.
Keywords:
Acinetobacter baumanniiEndolysinStaphylococcus aureusdeletion mutantsresistance

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