Antimicrobial Photodynamic Therapy with Ga-Protoporphyrin Derivatives Against Pathogenic Bacteria
Abstract
Bacterial pathogens have the ability to acquire hemin through different mechanisms. One mechanism is through cell-surface hemin receptors (CSHRs), which are capable of rapid hemin recognition and make the bacteria vulnerable to antimicrobial photodynamic inactivation (aPDI). The work presented here focuses on gallium protoporphyrin IX (GaPpIX) as a photosensitizer for aPDI against staphylococci. GaPpIX is rapidly uptaken by CSHR-expressing bacteria, which is easily detected by fluorescence within minutes of exposure. Assessment of GaPpIX as a photosensitizer against laboratory strains of Staphylococcus aureus, clinical isolates of methicillin-resistant S. aureus (MRSA), and S. epidermis shows aPDI activity at low micromolar levels following 15 minutes of exposure to a compact fluorescent light bulb, and nanomolar levels following 10 seconds of exposure to a 405-nm light emitting diode array. The aPDI activity of GaPpIX was much greater than that of unmetallated protoporphyrin (PpIX), and several times more potent than that of TMPyP, a leading cationic photosensitizer. The photosensitizing properties of GaPpIX could be further potentiated by its incorporation into hemoglobin (GaHb) and mounting this protein onto 10-nm silver nanoparticles (AgNPs). The aPDI activities of the 10-nm GaHb-AgNP constructs against clinical MRSA isolates were several times more potent than GaPpIX on a per mole basis, and exhibited low toxicity against keratinocytes.
Degree
Ph.D.
Advisors
Wei, Purdue University.
Subject Area
Organic chemistry|Nanotechnology|Microbiology|Pathology
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