Lethal interaction between heat and methylene blue in Escherichia coli.

Hyperthermia treatment is shown to act synergistically with methylene blue (MB), from the end point of lethality in Gram-negative Escherichia coli bacteria. That this lethality is correlated to the damage produced in DNA by the dye is deduced from the fact that bacteria differing in capacity for repair are almost equally sensitive to heat, but differ considerably in sensitivity to concomitant heat and dye treatment. It is demonstrated that the damage is repairable by the excision-repair system. The role of temperature seems to be that of facilitating the incorporation of the dye, which enables the latter to intercalate into the DNA. Ability of the outer membrane of E. coli AB1157 bacteria to act as a barrier to the penetration of MB remains almost intact up to 46 degrees C, but above this temperature it seems to disrupt abruptly (but reversibly), leading to inactivation of the cells by the dye. Since hyperthermia is in current use for the treatment of cancer, it is suggested that if this synergism also exists in mammalian cells, MB could eventually be used independently of its photodynamic action as an adjuvant in cancer therapy.