Presentation Title: Antimicrobial photodynamic therapy of Staphylococcus aureus using non-iron hemin analogs
Author Name(s): Benjamin Washer *, Badhu Sivasubramaniam*, Yuichiro Watanabe*, Alex Wei*
Author Department and School Affiliation: * Department of Chemistry, Purdue University, West Lafayette, Indiana 47907
Abstract: Antimicrobial photodynamic therapy (aPDT) utilizes photosensitizers (PS) to generate bursts of singlet oxygen and other reactive oxygen species (ROS) upon visible-light irradiation1 . Non-iron metalloprotoporphyrins mimicking hemin have effective antimicrobial activity against both Gram-positive and –
negative bacteria.2 Our lab has established that PS based on protoporphyrin IX (PpIX) derivatives with noniron centers (Al-PpIX, Ga-PpIX, In-PpIX) are more potent than other PS such as TmPyP. 3 Our recent studies with silver nanoparticle conjugated Ga-PpIX unit, stabilized by hemoglobin have shown higher
aPDI activity compared to Ga-PpIX itself.4 These PS are taken up within seconds by S. aureus and MRSA, attributable to direct uptake mechanisms via cell-surface hemin receptors, namely iron-regulated surface determinant (Isd) proteins. The PpIX derivatives appear to have differences in their mechanism of action
against S. aureus, dominated either by generation of singlet oxygen or other ROS. Al-PpIX and Ga-PpIX have more potent aPDT activity against S. aureus than In-PpIX, with 3-log reduction in CFU/mL at 0.03 μM after a 30-second irradiation using a 405-nm LED source. aPDT mediated by photoactive hemin analogs
can be a potential alternate therapy for many multidrug-resistant pathogens that actively express hemin acquisition systems, and a are promising method for treating topical and oral bacterial infections.
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3) Morales, A, V., Maltais, T. R., Lin, L., Younis, W., Kadasala, N. R., Seleem, M., Wei, A., ACS Infect. Dis. 2018,
4) Morales, A, V., Lin, L., Sivasubramaniam, B., Yermembetova, A., Abutaleb, S, N., Seleem, M., Wei, A.,
Nanoscale 2020 (status = manuscript under revision).