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A new pleuromutilin candidate with potent antibacterial activity against Pasteurella multocida

Yunxing Fu1, Lijun Ma2, Yunpeng Yi1

  • 1Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, PR China; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, 730050, China.

Microbial Pathogenesis
|December 12, 2018
PubMed

Insights

The novel antimicrobial 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM) shows potent activity against Pasteurella multocida serotype A. DPTM effectively reduced bacterial load and mortality in a lung infection model.

Area of Science:

  • Veterinary Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Pasteurella multocida is a significant pathogen causing respiratory infections in animals.
  • Novel antimicrobial agents are needed to combat bacterial infections, including those caused by P. multocida.

Purpose of the Study:

  • To evaluate the in vitro and in vivo antimicrobial activity of 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM) against Pasteurella multocida serotype A.

Main Methods:

  • Minimum Inhibitory Concentration (MIC) assays were performed to determine the lowest concentration of DPTM inhibiting bacterial growth.
  • Oxford Cup assays measured the zone of inhibition produced by DPTM.
  • Time-kill experiments assessed the rate of bacterial killing by DPTM.
  • A mouse lung infection model was used to evaluate DPTM's efficacy in vivo.

Main Results:

  • DPTM demonstrated potent in vitro activity against P. multocida serotype A, with a MIC of 0.781 μg/mL.
  • Significant inhibition zones were observed in Oxford Cup assays.
  • Time-kill experiments showed a rapid reduction in bacterial numbers, with 94.6% killing within 24 hours.
  • In vivo, DPTM significantly reduced mortality, bacterial load, and lung pathology in a P. multocida-induced pneumonia model.

Conclusions:

  • DPTM exhibits significant antimicrobial activity against Pasteurella multocida serotype A.
  • DPTM shows promise as a therapeutic agent for controlling or preventing P. multocida-associated pneumonia.
Keywords:
Antibacterial activityDPTMMicePasteurella multocida

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