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Mutations in the visA gene of Escherichia coli cause the mutant bacteria to die upon illumination with visible light. We confirmed genetically that the visA gene is a structural gene for ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1). Since other mutations in the genes involved in the biosynthesis of heme can cure the photosensitivity, the light-induced cell death appears to be brought about by the accumulation of protoporphyrin IX, one of the substrates of ferrochelatase. When cells are illuminated with visible light, protoporphyrin IX seems to produce an active species of oxygen (probably 1O2) that is harmful to the cells. This defect is the same as that associated with the human disease protoporphyria.

Quantitative changes in unmyelinated nerve fibres in sural nerves obtained at autopsy were evaluated in 28 normal adults. The following conclusions were reached. (1) The density of unmyelinated axons showed no significant correlation with age, but the densities of (2) Schwann cell subunits with axons, (3) Schwann cell subunits without axons, (4) single protrusions of Schwann cells and (5) collagen pockets, and (6) the mean number of Schwann cell profiles per axon, all showed positive correlations with age. Additionally, (7) the percentage of subunits containing unmyelinated axons and (8) the mean number of axons in single axon-containing Schwann cell subunits demonstrated negative correlations with age. The density of Schwann cell nuclei related to unmyelinated fibres did not show a significant change with age. The age-dependent changes in unmyelinated nerve fibres thus mainly consist of an increased production of processes by Schwann cells in the absence of cell multiplication. A decrease in unmyelinated nerve fibre density or a compensatory increase of small unmyelinated axons did not occur in these normal adults. In terms of relative sensitivity for the detection of the earliest changes in unmyelinated fibres, the indices (6) and (7) are considered to be useful and superior to the conventional assessment of unmyelinated axon density and diameter distribution. These two indices are not influenced by postmortem swelling of the axons and Schwann cells. Measurements of unmyelinated axon density and size distribution will continue to be useful in the assessment of more advanced pathological conditions.

Cells with a novel mutation that is lethal when the cells are exposed to visible light were isolated from Escherichia coli K-12. The mutation was mapped at 63 min on the linkage map of the E. coli chromosome, and the gene, designated visB, was cloned and sequenced. From its map position and the evidence that the gene product VisB exhibits homology with flavin monooxygenase of Pseudomonas fluorescens, the visB gene was deduced to be identical to the ubiH gene, which is a gene required for the biosynthesis of ubiquinone and is thought to be similar to the gene for flavin monooxygenase. The photosensitive phenotype appears to be due to the accumulation of the substrate for the reaction catalyzed by the visB (ubiH) gene product because other mutations that block earlier steps in the biosynthesis of ubiquinone can reverse the photosensitivity. The accumulated intermediates may produce active species of oxygen in the mutant bacteria upon illumination by visible light, and these active oxygen species may cause the death of the cells by a mechanism similar to that associated with mutations in visA (hemH).