Analysis of the bacterial heat shock response to photodynamic therapy-mediated oxidative stress.
Antimicrobial photodynamic therapy (PDT) has recently emerged as an effective modality for the selective destruction of bacteria and other pathogenic microorganisms. We investigated whether PDT induced protective responses such as heat shock proteins (HSPs) in bacteria. Using the photosensitizer Toluidine Blue O (TBO) at sublethal PDT conditions, a seven-fold increase in bacterial HSP GroEL and a three-fold increase in HSP DnaK were observed in Escherichia coli post PDT. Pretreatment with 50°C heat for 30 min reduced PDT killing in both E. coli and in Enterococcus faecalis, with the most pronounced inhibition occurring at 50 μm TBO with 5 J cm(-2) 635 nm light, where E. coli killing was reduced by 2 log(10) and E. faecalis killing was reduced by 4 log(10). Finally, inhibition of the highly conserved chaperone DnaK using a small molecule benzylidene lactam HSP inhibitor potentiated (but not significantly) the effect of PDT at a TBO concentration of 2.5 μm in E. faecalis; however, this effect was not observed in E. coli presumably because inhibitor could not gain access due to Gram-negative permeability barrier. Induction of HSPs may be a mechanism whereby bacteria could become resistant to PDT and warrants the need for further study in the application of dual PDT-HSP-inhibition therapies.
John Jay High School, Cross River, NY, USA.
Tyler G
TG
St Denis
Liyi
L
Huang
Tianhong
T
Dai
Michael R
MR
Hamblin
D001597:Benzylidene Compounds / Q000494:pharmacology*; D018834:Chaperonin 60 / Q000096:biosynthesis*; D013293:Enterococcus faecalis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018869:Heat-Shock Response / Q000187:drug effects / Q000528:radiation effects; D006358:Hot Temperature; D008027:Light; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013045:Species Specificity; D014048:Tolonium Chloride / Q000494:pharmacology*; D015854:Up-Regulation
D001597:Benzylidene Compounds; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D017319:Photosensitizing Agents; D014048:Tolonium Chloride; C063842:dnaK protein, E coli
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