Photodynamic therapy based on 5‐aminolevulinic acid and its use as an antimicrobial Agent

Abstract

Exogenous 5-aminolevulinic acid (ALA) is taken up directly by bacteria, yeasts, fungi, and some parasites, which then induces the accumulation of protoporphyrin IX (PPIX). Subsequent light irradiation of PPIX leads to the inactivation of these organisms via photodamage to their cellular structures. ALA uptake and light irradiation of PPIX produced by host cells leads to the inactivation of other parasites, along with some viruses, via the induction of an immune response. ALA-mediated PPIX production by host cells and light irradiation result in the inactivation of other viruses via either the induction of a host cell response or direct photodynamic attack on viral particles. This ALA-mediated production of light-activated PPIX has been extensively used as a form of photodynamic therapy (PDT) and has shown varying levels of efficacy in treating conditions that are associated with microbial infection, ranging from acne and verrucae to leishmaniasis and onychomycosis. However, for the treatment of some of these conditions by ALA-based PDT, the role of an antimicrobial effect has been disputed and in general, the mechanisms by which the technique inactivates microbes are not well understood. In this study, we review current understanding of the antimicrobial mechanisms used by ALA-based PDT and its role in the treatment of microbial infections along with its potential medical and nonmedical applications.

An in vitro study of the photodynamic effect of rose bengal on trichophyton rubrum

“…These radicals react with oxygen to produce oxygenated species. In Type II reactions, the activated photosensitizer transfers its energy directly to oxygen forming singlet oxygen known as highly reactive oxygen species (ROS) [14][15][16][17]. Both these reactions cause cellular toxicity and can occur simultaneously; however, the type of reaction occurring is dependent on the photosensitizer used, the substrate, oxygen concentration and photosensitizer substrate binding [18].…”

Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester

“…Because the biosynthesis of 5-ALA is the rate limiting step in these biosynthetic pathways, when an excessive amount of this molecule is provided exogenously and taken up by cells, photoactive porphyrins accumulate, particularly in rapidly growing cells such as bacteria thereby giving a degree of selective targeting [12].…”

“…Uptake of 5-ALA and subsequent synthesis and accumulation of porphyrins is highest in cells that are rapidly dividing, with high metabolic activity, which results in selectivity towards bacteria over normal host cells of the cell [12]. Recently, 5-ALA-mediated PACT has been investigated to inactivate several important antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus 3 (MRSA) [13,14] and multidrug-resistant (MDR) Escherichia coli [14,15].…”

Mechanistic Aspects of the Photodynamic Inactivation of Vancomycin-Resistant Enterococci Mediated by 5-Aminolevulinic Acid and 5-Aminolevulinic Acid Methyl Ester

“…When provided exogenously, 5-ALA results in the accumulation of photoactive porphyrins within the targeted cells. This accumulation is more pronounced in cells with high rates of metabolic activity, such as cancer cells, inflammatory cells, virally infected cells, and bacteria in particular [17]. Recently, 5-ALA-mediated PACT has been investigated to inactivate several important antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) [24], multidrug-resistant (MDR) Escherichia coli [27], and MDR Pseudomonas aeruginosa [14].…”