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Resistance of Gram-negative bacteria to photodynamic inactivation by uncharged porphyrins and illumination led to the search for other approaches for overcoming this problem. In this chapter, a series of approaches used by several research groups to induce photokilling of Gram-negative bacteria are described. One general approach was to use polycationic compounds such as polymyxin nonapeptide, polylysine, or polyethyleneimine to act as a vehicle for bringing the exogenous uncharged photosensitizer through the outer membrane and into a close interaction with the inner membrane. The polycationic compounds can be free or conjugated covalently to the photosensitizer. Another approach taken was to use positively charged photosensitizers such as meso-substitutes, porphyrins, phthalocyanines, or phenothiazines. Photoinactivation of Gram-negative bacteria by their endogenous photosensitizer is described as another type of approach. New approaches include the photoinactivation by encapsulated photosensitizers or by chemiluminescence. Damages to the inner membrane and changes in the ultrastructure upon photoinactivation by the above approaches are described and the mode of the photosensitization action is discussed.

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