Photodynamic antimicrobial chemotherapy in mice with Pseudomonas aeruginosa-infected wounds

PLoS One. 2020 Sep 2;15(9):e0237851. doi: 10.1371/journal.pone.0237851. eCollection 2020.

Abstract

This study examined the antibacterial effect of protoporphyrin IX-ethylenediamine derivative (PPIX-ED)-mediated photodynamic antimicrobial chemotherapy (PPIX-ED-PACT) against Pseudomonas aeruginosa in vitro and in vivo. PPIX-ED potently inhibited the growth of Pseudomonas aeruginosa by inducing reactive oxygen species production via photoactivation. Atomic force microscopy revealed that PPIX-ED-PACT induced the leakage of bacterial content by degrading the bacterial membrane and wall. As revealed using acridine orange/ethidium bromide staining, PPIX-ED-PACT altered the permeability of the bacterial membrane. In addition, the antibacterial effect of PPIX-ED-PACT was demonstrated in an in vivo model of P. aeruginosa-infected wounds. PPIX-ED (100 μM) decreased the number of P. aeruginosa colony-forming units by 4.2 log10. Moreover, histological analysis illustrated that the wound healing rate was 98% on day 14 after treatment, which was 10% higher than that in the control group. According to the present findings, PPIX-ED-PACT can effectively inhibit the growth of P. aeruginosa in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Cell Membrane / drug effects
  • Cell Membrane / radiation effects
  • Ethylenediamines / chemistry
  • Ethylenediamines / pharmacology
  • Ethylenediamines / therapeutic use
  • Female
  • Light
  • Mice
  • Mice, Inbred BALB C
  • Microbial Viability / drug effects
  • Models, Biological
  • NIH 3T3 Cells
  • Photobleaching
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Protoporphyrins / chemistry
  • Protoporphyrins / pharmacology
  • Protoporphyrins / therapeutic use
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / physiology*
  • Pseudomonas aeruginosa / radiation effects
  • Wound Healing / drug effects
  • Wound Infection / drug therapy*
  • Wound Infection / microbiology*

Substances

  • Anti-Bacterial Agents
  • Ethylenediamines
  • Photosensitizing Agents
  • Protoporphyrins
  • ethylenediamine
  • protoporphyrin IX

Grants and funding

This study was supported by the national Mega-project for Innovative Drugs (2019ZX09721001-006-001 to Ge Hong) and the medical and health science and technology innovation project of Chinese Academy of Medical Science (2019-I2M-1-005 to Ge Hong). The funder provided support in study design.