Komerik, Nurgul; (2001) Susceptibility of mucositis-associated gram-negative bacteria to photodynamic action. Doctoral thesis (Ph.D.), University College London.

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Abstract

Opportunistic pathogens such as enteric Gram-negative bacilli in the oral cavity of cancer patients undergoing radio/chemotherapy may contribute to the mucosal lesions (mucositis) caused by these cytotoxic therapies and also constitute a source of infection. What is more, resistance of organisms to conventional antibacterial regimes is a growing cause of concern. Photodynamic action (PDA), elimination of target cells by use of a photosensitising compound in combination with light, may be a potential alternative therapeutic regime for topical infections. This study evaluated the effectiveness of PDA on a number of potential pathogens associated with mucositis. The PDA of toluidine blue O (TBO) with light from a HeNe gas laser on the viability of a range of Gram-negative bacilli considered to play a role in mucositis was assessed. The susceptibility of other opportunistic pathogens together with the indigenous oral flora was also studied. Gram-negative bacilli were shown to be killed by PDA the effectiveness of which was dependent on both the TBO concentration and light dose. All the organisms tested were susceptible to PDA, indicating its broad spectrum effect. Studies of the effects of physiological factors on the efficacy of PDA showed that bacteria could be killed under all the physiological conditions tested. However, PDA in saliva and serum was not as effective as it was in saline, and greater kills were obtained at increased pHs. Mechanistic studies demonstrated that TBO was an effective photosensitiser when outside the bacteria and indicated that the outer membrane may be the site where initial photo-damage takes place through the production of singlet oxygen and, to a lesser extent, hydroxyl radicals. PDA was also shown to impair some virulence factors (lipopolysaccharide and proteolytic enzyme activity) of bacteria. An animal study was conducted to elucidate any possible adverse effects on host tissues and this demonstrated that at all doses tested, PDA had no adverse effect on the buccal mucosa of rats. Furthermore, fluorescence microscopy studies demonstrated a high level of TBO in the epithelium but no detectable levels in the underlying connective tissue. Although it was shown that killing by PDA of both laboratory and clinical strains of organisms is possible, further animal studies are needed to establish the effectiveness of this novel technique for the treatment of topical, localised infections.

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