Science against microbial pathogens: photodynamic therapy approaches Constance L.L. Saw 1 1 Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, 08854 New Jersey, USA. E-mail: constancesaw@gmail.com There is an emerging area of research to identify the application of photodynamic therapy (PDT) as a means to kill microbial pathogens. In fact, the first recorded observation in more than 100 years ago of photodynamic processes was inactivation of microorganism. In this volume of the Formatex Microbiology book titled: Science against microbial pathogens: communicating current research and technological advances, this chapter will focus on the use of photosensitizer and light as anti-microbial agent against various microbes in different settings. The mechanism of action of PDT inactivating microorganisms, anti-microbial photosensitizing agents and light sources used for eliminating microorganisms will be covered. The success and challenges of using PDT to eradicate bacteria including antibiotic resistant bacteria will be discussed. Keywords PDT; against microbial; antimicrobial; photosensitizers; light 1. Introduction There is an emerging area of research to identify the application of photodynamic therapy (PDT) as a means to kill microbial pathogens. In fact, the first recorded observation in more than 100 years ago of photodynamic processes was inactivation of microorganism, paramecia by Oscar Raab [1]. It was an incidental finding that in the presence of acridine and illumination from a thunderstorm, resulted in the death of paramecia. He demonstrated that the death of paramecia was possible only when light and acridine were present. Additionally, it was found that the toxic effect was not due to heat [2] and the term ‘photodynamic reaction’ was coined in 1904 [3]. For detailed history of PDT, please refer to existing literature [4]. PDT is based on the dual selectivity: (i) selective localization of photosensitizer targeting at tumor or other lesion of interest and (ii) specific delivery of light eliciting the PDT at the target sites. Although PDT was originally developed as a cancer therapy approach and it is still being developed [5], furthermore it has already been developed as a treatment for age-related macular degeneration [6, 7], psoriasis [8, 9], barrett’s oesophagus [10, 11] etc. Taking PDT in cancer as a classic example, after photosensitizers have accumulated in pre-cancerous and cancerous tissues, then appropriate light of specific wavelength will be applied, causing the tumor undergo photo-induced chemical reactions that cause apoptosis or necrosis [12]. Similarly, the uptake of photosensitizers and upon activation by light, PDT induced destruction to pathological or infectious tissues/regions is the common working mechanism among various diseases, including infection. 2. Mechanism of photodynamic reaction There are two mechanisms involved in the photodynamic reaction / PDT. Upon irradiation with an appropriate wavelength of light, a photosensitizer will be activated from its lowest energy ground state to a higher energy triplet stage, which will further react directly with biomolecules to produce free radicals (Type I mechanism) or react with oxygen to form reactive singlet oxygen, 1 O 2 (Type II mechanism) [13]. 1 O 2 is very reactive and has strong oxidizing power that can produce potent cytotoxic effects [4]. In cells, it has been reported that 1 O 2 has a lifetime of less than 0.05 s and a maximal diffusion distance of 0.02 m from the site of its production [14], such characteristics explain in part the specificity of photodynamic reaction for PDT in cancers or photodynamic inactivation (PDI) for killing of antibiotic resistant bacteria. Therefore, conventionally it is thought that the targets of PDT are places where the photosensitizer is localized [15]. However, recent findings suggest that even if some photosensitizers do not bind to the bacteria, yet can cause PDI of bacteria if the distance between the singlet oxygen source and bacteria is close [16]. Please see further discussion in section 5, mechanism of PDI damage to bacteria. 3. The need to search for new antibacterial therapeutics Due to the emergence of antibiotic resistance bacteria, particularly with Staphylococcus aureus after the introduction of methicillin [17], there is an urgent need to find alternative antibacterial therapeutics. While hospital-associated Methicillin-resistant Staphylococcus aureus (HA-MRSA) was once observed in immunocompromised hosts, the rapid emergence of community-associated MRSA (CA-MRSA) has caused a concern and the global epidemiology of CA- MRSA appears to be heterogenous [18]; moreover, both HA-MRSA and CA-MRSA have been found to circulate in community due to loose used of terms [19]. Since the fist report of vancomycin-intermediate Staphylococcus aureus 668 ©FORMATEX 2011 Science against microbial pathogens: communicating current research and technological advances A. Méndez-Vilas (Ed.) ______________________________________________________________________________