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Updated: Jun 27, 2026

Production and Testing of Antimicrobial Peptides and Their Mimics
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Production and Testing of Antimicrobial Peptides and Their Mimics

Published on: April 10, 2026

3‑Methylthiopropionic Acid Kills Carbapenem-Resistant Klebsiella pneumoniae by Disrupting Membrane Integrity and

Lirui Ge1, Liang Zhao1, Saiwa Liu1

  • 1State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

JACS Au
|June 26, 2026
PubMed

Insights

New Delhi metallo-β-lactamase (NDM) resistance in Klebsiella pneumoniae is linked to metabolic changes. Researchers identified 3-methylthiopropionic acid (MTPA) as a metabolite that kills NDM-producing bacteria, offering a new strategy against carbapenem resistance.

Area of Science:

  • Microbiology
  • Metabolomics
  • Drug Discovery

Background:

  • The spread of New Delhi metallo-β-lactamase (NDM) genes confers resistance to carbapenems in Klebsiella pneumoniae.
  • This resistance poses a significant global health challenge, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To investigate the metabolic underpinnings of NDM-mediated carbapenem resistance in Klebsiella pneumoniae.
  • To identify potential therapeutic targets or agents derived from metabolic reprogramming.

Main Methods:

  • Comparative metabolomics was used to analyze metabolic differences in NDM-producing Klebsiella pneumoniae.
  • In vitro bactericidal assays and murine infection models were employed to evaluate the efficacy of identified metabolites.
  • Integrated transcriptomics and metabolomics were performed to elucidate the mechanism of action.

Main Results:

  • NDM-mediated resistance is associated with significant metabolic reprogramming in Klebsiella pneumoniae.
  • 3-methylthiopropionic acid (MTPA), an endogenous metabolite, demonstrated potent bactericidal activity against NDM-producing strains.
  • MTPA disrupts bacterial membrane integrity, energy production (ATP depletion), and induces reactive oxygen species (ROS) via Complex I inhibition.
  • Treatment with MTPA significantly improved survival rates in a murine model of Klebsiella pneumoniae infection.

Conclusions:

  • Metabolic reprogramming is a key factor in carbapenem resistance mediated by NDM genes.
  • MTPA represents a promising endogenous agent for combating NDM-producing Klebsiella pneumoniae infections.
  • Targeting pathogen metabolic pathways offers a viable chemical strategy against antibiotic resistance.
Keywords:
3-methylthiopropionic acidKlebsiella pneumoniaeblaNDM‑1blaNDM‑5drug resistancemetabolomics

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