Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo
2017 (Engelska)Ingår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 7, artikel-id 14Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
Francisella tularensis is an intracellular bacterium and as such is expected to encounter a continuous attack by reactive oxygen species (ROS) in its intracellular habitat and efficiently coping with oxidative stress is therefore essential for its survival. The oxidative stress response system of F tularensis is complex and includes multiple antioxidant enzymes and pathways, including the transcriptional regulator OxyR and the H2O2-decomposing enzyme catalase, encoded by katG. The latter is regulated by OxyR. A deletion of either of these genes, however, does not severely compromise the virulence of F tularensis and we hypothesized that if the bacterium would be deficient of both catalase and OxyR, then the oxidative defense and virulence of F tularensis would become severely hampered. To test this hypothesis, we generated a double deletion mutant, Delta oxyR/Delta katG, of F tularensis LVS and compared its phenotype to the parental LVS strain and the corresponding single deletion mutants. In accordance with the hypothesis, Delta oxyR/Delta katG was distinctly more susceptible than Delta oxyR and Delta katG to H2O2, ONOO-, and O-2(-), moreover, it hardly grew in mouse-derived BMDM or in mice, whereas Delta katG and Delta oxyR grew as well as F tularensis LVS in BMDM and exhibited only slight attenuation in mice. Altogether, the results demonstrate the importance of catalase and OxyR for a robust oxidative stress defense system and that they act cooperatively. The lack of both functions render F tularensis severely crippled to handle oxidative stress and also much attenuated for intracellular growth and virulence.
Ort, förlag, år, upplaga, sidor
2017. Vol. 7, artikel-id 14
Nyckelord [en]
Francisella tularensis, OxyR, KatG, oxidative stress, virulence
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Mikrobiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-131634DOI: 10.3389/fcimb.2017.00014ISI: 000392532700001PubMedID: 28174696Scopus ID: 2-s2.0-85012149805OAI: oai:DiVA.org:umu-131634DiVA, id: diva2:1078033
2017-03-022017-03-022023-03-24Bibliografiskt granskad