title: Modulation of virulence in Acinetobacter baumannii cells surviving photodynamic treatment with toluidine blue.
abstract: BACKGROUND
  Widespread resistance to antimicrobial agents has led to a dearth of therapeutic choices in treating Acinetobacter baumannii infections, leading to new strategies for treatment being needed. We evaluated the effects of photodynamic therapy (PDT) as an alternative antimicrobial modality on the virulence features of cell-surviving PDT.
  
  
  METHODS
  To determine the sublethal PDT (sPDT), a colistin-resistant, extensively drug-resistant A. baumannii (CR-XDR-AB) clinical isolate and A. baumannii and ATCC 19606 strains, photosensitized with toluidine blue O (TBO), were irradiated with light emitting diodes, following bacterial viability measurements. The biofilm formation ability, outer membrane (OM) integrity, and antimicrobial susceptibility profiles were assessed for cell-surviving PDT. The effects of sPDT on the expression of virulent genes were evaluated by real-time quantitative reverse transcription PCR (qRT-PCR).
  
  
  RESULTS
  sPDT resulted in the reduction of the biofilm formation capacity, and its metabolic activity in strains. The OM permeability and efflux pump inhibition of the sPDT-treated CR-XDR-AB cells were increased; however, there was no significant change in OM integrity in ATCC 19606 strain after sPDT. sPDT reduced the minimum inhibitory concentrations of the most tested antimicrobials by ≥2-fold in CR-XDR-AB. lpsB, blsA, and dnaK were upregulated after the strains were treated with sPDT; however, a reduction in the expression of csuE, epsA, and abaI was observed in the treated strains after sPDT.
  
  
  CONCLUSIONS
  The susceptibility of CR-XDR-AB to a range of antibiotics was enhanced following sPDT. The virulence of strains is reduced in cells surviving PDT with TBO, and this may have potential implications of PDT for the treatment of A. baumannii infections.
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Pourhajibagher
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Boluki
authors.affiliation: Laser Research Center of Dentistry, Dental Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nasim
authors.initials: N
authors.lastname: Chiniforush
authors.affiliation: Pediatrics Infectious Disease Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Pourakbari
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Farshadzadeh
authors.affiliation: Private Practice, Tehran, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Ghorbanzadeh
authors.affiliation: Department of Microbiology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Aziemzadeh
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Laser Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: abahador@sina.tums.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Bahador
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000472:pathogenicity* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D004203:Disinfection / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D014048:Tolonium Chloride / Q000008:administration & dosage*; D014774:Virulence / Q000187:drug effects* / Q000502:physiology
chemical_list: D017319:Photosensitizing Agents; D014048:Tolonium Chloride
keywords: Acinetobacter baumannii; Antimicrobial resistance; Photodynamic therapy; Sublethal; Virulence genes