Agr function is upregulated by photodynamic therapy for Staphylococcus aureus and is related to resistance to photodynamic therapy

Microbiol Immunol. 2013 Aug;57(8):547-52. doi: 10.1111/1348-0421.12070.

Abstract

Photodynamic therapy (PDT) has been considered a feasible alternative for antimicrobial therapy of multidrug-resistant pathogens. However, bacterial response mechanisms against PDT-generated photo-oxidative stress remain largely unknown. Herein, it is shown that the accessory gene regulator Agr is involved in Staphylococcus aureus response to photo-oxidative stress generated by laser-induced PDT with the photosensitizer chlorin e6 . Transcriptional profiling revealed that sublethal PDT induces a general stress response and also activates Agr-dependent gene regulation. Moreover, mutant S. aureus lacking Agr function showed hypersusceptibility to two independent PDT conditions with higher energy densities, demonstrating Agr-dependent S. aureus resistance against PDT.

Keywords: accessory gene regulator; antimicrobial therapy; multidrug resistance; photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Chlorophyllides
  • Drug Resistance, Bacterial*
  • Gene Expression Regulation, Bacterial / drug effects
  • Humans
  • Photochemotherapy
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / therapeutic use
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Up-Regulation / drug effects*

Substances

  • Agr protein, Staphylococcus aureus
  • Bacterial Proteins
  • Chlorophyllides
  • Photosensitizing Agents
  • Porphyrins
  • Trans-Activators
  • phytochlorin