AUTHOR=Bourret Travis J. , Lawrence Kevin A. , Shaw Jeff A. , Lin Tao , Norris Steven J. , Gherardini Frank C. 

TITLE=The Nucleotide Excision Repair Pathway Protects Borrelia burgdorferi from Nitrosative Stress in Ixodes scapularis Ticks

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01397

DOI=10.3389/fmicb.2016.01397

ISSN=1664-302X

ABSTRACT=<p>The Lyme disease spirochete <italic>Borrelia burgdorferi</italic> encounters a wide range of environmental conditions as it cycles between ticks of the genus <italic>Ixodes</italic> and its various mammalian hosts. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are potent antimicrobial molecules generated during the innate immune response to infection, however, it is unclear whether ROS and RNS pose a significant challenge to <italic>B. burgdorferi in vivo</italic>. In this study, we screened a library of <italic>B. burgdorferi</italic> strains with mutations in DNA repair genes for increased susceptibility to ROS or RNS <italic>in vitro</italic>. Strains with mutations in the methyl-directed mismatch repair gene <italic>mutS1</italic> are hypersensitive to killing by ROS, while strains lacking the nucleotide excision repair (NER) gene <italic>uvrB</italic> show increased susceptibility to both ROS and RNS. Therefore, <italic>mutS1</italic>-deficient and <italic>uvrB</italic>-deficient strains were compared for their ability to complete their infectious cycle in Swiss Webster mice and <italic>I. scapularis</italic> ticks to help identify sites of oxidative and nitrosative stresses encountered by <italic>B. burgdorferi in vivo</italic>. Both <italic>mutS1</italic> and <italic>uvrB</italic> were dispensable for infection of mice, while <italic>uvrB</italic> promoted the survival of spirochetes in <italic>I. scapularis</italic> ticks. The decreased survival of <italic>uvrB</italic>-deficient <italic>B. burgdorferi</italic> was associated with the generation of RNS in <italic>I. scapularis</italic> midguts and salivary glands during feeding. Collectively, these data suggest that <italic>B. burgdorferi</italic> must withstand cytotoxic levels of RNS produced during infection of <italic>I. scapularis</italic> ticks.</p>