Molecules with a pronounced positive charge are able to effectively target bacteria (both Gram (+) and Gram (-)) for photodestruction. This is because the the outer-membrane permeability barrier typical of Gram (-) bacteria is disrupted by cationic molecules, while Gram (+) species have negatively charged but permeable cell walls. We have discovered several novel classes of cationic PS;
Considerable data on the structure-function relationships of these molecules and their efficiency in photodynamic inactivation of a wide range of pathogenic microorganisms has been obtained. Gram-positive, Gram-negative bacteria, mycobacteria, yeasts, filamentous fungi and even bacterial spores can all be effectively eradicated with more than 6 logs of killing. Multi-antibiotic resistant bacteria can be killed as easily as naive strains. Multi-drug resistance pumps can be overcome. PDT can also photoinactivate virulence factors and toxins that are secreted by pathogens.
Hamblin MR, O’Donnell DA, Murthy N, Rajagopalan K, Michaud N, Sherwood ME, Hasan T. Polycationic photosensitizer conjugates: photodynamic inactivation of bacteria depends on conjugate structure and Gram classification. J Antimicrob Chemother 2002;49(6):941-51.
Gad F, Zahra T, Hasan T, Hamblin MR. Photodynamic inactivation of Gram-positive pathogenic bacteria: effect of growth phase and extracellular slime. Antimicrob Agents Chemother, 2004; 48(6):2173-8.
Demidova TN , Hamblin MR. Photodynamic therapy targeted to pathogens. Int J Immunopathol Pharmacol 2004;17(3): 245-54.
Demidova TN , Hamblin MR. Effect of cell-photosensitizer binding and cell density on microbial photoinactivation. Antimicrob Agents Chemother; 2005;49(6):2329-35
Demidova TN, Hamblin MR . Photodynamic inactivation of Bacillus spores mediated by phenothiazinium dyes. Appl Environ Microbiol, 2005, 71: 6918–6925
Tegos GP, Demidova TN, Arcila-Lopez D, Lee H, Gali H, Wharton T, Hamblin MR. Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chem Biol, 2005, 12: 1127-1135
Tegos GP, Hamblin MR. Phenothiazinium antimicrobial photosensitizers are substrates of bacterial multidrug resistance pumps, Antimicrob Agents Chemother, 2006, 50: 196-203
Tegos GP, Anbe M, Yang C, Demidova TN, Satti M, Mroz P, Janjua S, Gad F and Hamblin MR. Protease stable polycationic photosensitizer conjugates between polyethyleneimine and chlorin(e6) for broad spectrum antimicrobial photoinactivation. Antimicrob Agents Chemother, 2006, 50: 1402-1410.
