Project #12627
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#12627 : Role of small non coding RNAs in the adaptive response to oxidative stress in pathogenic Leptospira
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Name of Applicant : NADIA BENAROUDJ
Date of application : 28-11-2018
Unit : Biology of Spirochetes
Location : 12-3-17A
Phone : 3746
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@ PI-Mail :

Project context and summary :

Pathogen leptospires are responsible for the zoonotic disease leptospirosis. This neglected but emerging infectious disease has a worldwide distribution and affects people from developing countries, mostly under tropical areas. The clinical manifestations of this infection range from a febrile state to a severe life-threatening form characterized by multiple organ hemorrhages. More than one million cases of leptospirosis are currently reported annually in the word, with 10% of mortality. Leptospira penetrate hosts and rapidly disseminate to target organs (including kidney, liver, lungs) throughout the bloodstream. They are not obligatory intracellular pathogen but they can transiently persist inside macrophages. Due to the difficulty of gene inactivation in pathogen Leptospira, their study is hampered and limited. Thus, their virulence mechanisms and how they survive inside hosts remain largely unknown. During infection, Leptospira are confronted with dramatic adverse environmental changes such as deadly reactive oxygen species (ROS). Defenses against ROS, e.g. peroxidase activity, are crucial for Leptospira virulence. In previous studies, we have identified by RNASeq the cellular factors solicited by Leptospira interrogans to adapt to an oxidative stress and determined the regulons of the two peroxide stress regulators PerR1 and PerR2. We aim now at studying how small non coding RNAs participate in the adaptive response to oxidative stress in pathogen Leptospira. Regulation of any predicted small non coding RNAs will be examined in the RNASeq data we have already obtained.

Related team publications :
Kebouchi, M., Saul, F., Taher, R., Landier, A., Beaudeau, B., Dubrac, S., Weber, P., Haouz, A., Picardeau, M., and Benaroudj, N. (2018) Structure and function of the Leptospira interrogans peroxide stress regulator (PerR), an atypical PerR devoid of a structural metal-binding site. J. Biol. Chem. 293(2):497-509, DOI:10.1074/jbc.M117.804443
Picardeau, M. (2017) Virulence of the zoonotic agent of leptospirosis: still terra incognita? Nat. Rev. Microbiol. 15(5):297-307, DOI:10.1038/nrmicro.2017.5
Zhukova, A., Fernandes, L.G., Hugon, P., Papas, C.J., Sismeiro, O., Coppée, J.Y., becavin, C., malabat, C., Eshghi, A., Zhang, J.J., Yang, F.X., Picardeau, M. (2017) Genome-Wide Transcriptional Start Site Mapping and sRNA Identification in the Pathogen Leptospira interrogans. Front. Cell. Infect. Microbiol. jan 19;7:10, DOI:10.3389/fcimb.2017.00010
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Project Type : Short
Status : Closed
Publication : doi: 10.1371/journal.ppat.1008904
Global Satisfaction for this application : Excellent (5/5)

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