Borrelia burgdorferi membranes are the primary targets of reactive oxygen species.
Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H(2)O(2) had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H(2)O(2) show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle.
Boylan
Julie A
JA
National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, 903 S 4th Street, Hamilton, MT 59840, USA.
Lawrence
Kevin A
KA
Downey
Jennifer S
JS
Gherardini
Frank C
FC
D025065:Borrelia burgdorferi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004269:DNA, Bacterial / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000032:analysis / Q000037:antagonists & inhibitors; D008854:Microscopy, Electron; D009154:Mutation / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000494:pharmacology*
D004269:DNA, Bacterial; D008055:Lipids; D016877:Oxidants; D017382:Reactive Oxygen Species