Abstract

Since the early work of the 1900s it has been axiomatic that photodynamic action requires the presence of sufficient ambient oxygen. The Type I photochemical pathway involves electron transfer reactions leading to the production of reactive oxygen species (superoxide, hydrogen peroxide, and hydroxyl radicals), while the Type II pathway involves energy transfer from the PS (photosensitizer) triplet state, leading to production of reactive singlet oxygen. The purpose of the present review is to highlight the possibility of oxygen-independent photoinactivation leading to the killing of pathogenic bacteria, which may be termed the “Type III photochemical pathway”. Psoralens can be photoactivated by ultraviolet A (UVA) light to produce DNA monoadducts and inter-strand cross-links that kill bacteria and may actually be more effective in the absence of oxygen. Tetracyclines can function as light-activated antibiotics, working by a mixture of oxygen-dependent and oxygen independent pathways. Again, covalent adducts may be formed in bacterial ribosomes. Antimicrobial photodynamic inactivation can be potentiated by addition of several different inorganic salts, and in the case of potassium iodide and sodium azide, bacterial killing can be achieved in the absence of oxygen. The proposed mechanism involves photoinduced electron transfer that produces reactive inorganic radicals. These new approaches might be useful to treat anaerobic infections or infections in hypoxic tissue.

Highlights

  • The ever-growing development of antibiotic resistance amongst pathogenic bacteria and other microorganisms has led to the prediction of the “end of the antibiotic era” [1]

  • Antimicrobial photodynamic inactivation can be potentiated by addition of several different inorganic salts, and in the case of potassium iodide and sodium azide, bacterial killing can be achieved in the absence of oxygen

  • Around the 1990s, photodynamic therapy” (PDT) started to be studied as an antimicrobial technique, when it was discovered that Gram-negative bacteria that had been previously thought to be resistant to PDT [7,8], could be efficiently killed by using PS with cationic charges [9] or other modifications to the procedure [10,11]

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Summary

Introduction

The ever-growing development of antibiotic resistance amongst pathogenic bacteria and other microorganisms has led to the prediction of the “end of the antibiotic era” [1]. The fear has been voiced that we could return to an age when even minor injuries could prove fatal when infections set in, and eventually lead to sepsis. The O’Neill report [2] caused widespread consternation with its prediction of 300 million extra deaths and a cost of $100 trillion by 2050 if nothing were done to halt the spread of antibiotic resistance. There has been a worldwide effort to discover alternative antimicrobial technologies, which will kill multi-drug resistant microbial species, as well as not cause the development of resistance themselves. One of the leading candidates for this new antimicrobial approach is antimicrobial photodynamic inactivation (aPDI)

Antimicrobial Photodynamic Inactivation
Type I and Type II Photochemical Mechanisms
Infections in Hypoxic and Anaerobic Tissue Environments
Type III Photochemical Mechanism
Psoralens
Tetracyclines
Inorganic Salts
Findings
Discussion and Conclusions
Full Text
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