Tetrahydroporphyrin-tetratosylate (THPTS)-based photodynamic inactivation of critical multidrug-resistant bacteria in vitro

Background: Photodynamic inactivation (PDI) is a promising approach to treat multidrug-resistant infections. However, effectiveness of PDI is limited, particularly in Gram-negative bacteria. The use of photosensitizer (PS) 3,3',3 '',3 '''-(7,8,17,18-tetrahydro-21H,23H-porphyrine-5,10,15,20-tetrayl)tetrakis[1-methylpyridinium]tetratosylate (THPTS) and laser light has led to very promising results. This study focuses on the effects of THPTS in various critical multidrug-resistant bacterial strains and explores the possibility of light-emitting diode (LED)-based activation as a clinically more feasible alternative to laser light. Methods: THPTS was further chemically characterized and in vitro testing of PDI of different multidrugresistant bacterial strains was performed under various experimental conditions, including varying drug concentration, incubation time, light source (laser and LED) and light intensity, by determination of viable bacteria after treatment. The effect of hyaluronic acid as an adjuvant for medical applications was also evaluated. Results: Bacterial density of all investigated bacterial strains was reduced by several orders of magnitude, irrespective of multidrug-resistance or hyaluronic acid addition. The effect was less intense in Gramnegative strains (disinfection), and more pronounced in Gram-positive strains (sterilization), even at reduced THPTS concentrations or decreased light treatment intensity. Controls without THPTS or without light treatment did not indicate reduced bacterial density. Conclusions: PDI with THPTS and laser light was effective in all investigated bacterial strains. Gramnegative strains were less, but sufficiently, susceptible to PDI. Adding hyaluronic acid did not reduce the antibacterial treatment effect. LED-based PDI is equally effective when illumination duration is increased to compensate for reduced light intensity. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.