<i>Borrelia burgdorferi</i> membranes are the primary targets of reactive oxygen species

<jats:title>Summary</jats:title> <jats:p> 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 <jats:italic>Borrelia burgdorferi</jats:italic> contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of <jats:italic>B. burgdorferi</jats:italic> in the presence of 5 mM H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM <jats:italic>t</jats:italic> ‐butyl hydroperoxide or 10 mM H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> show no increase in DNA damage. Unlike most bacteria, <jats:italic>B. burgdorferi</jats:italic> incorporates ROS‐susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase‐treated <jats:italic>B. burgdorferi</jats:italic> 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 <jats:italic>B. burgdorferi</jats:italic> membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle. </jats:p>