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Adaptation of pathogenic Leptospira to oxidative stress

ABSTRACT: Pathogenic Leptospira spp. are the causative agents of the zoonotic disease leptospirosis. During infection, Leptospira are confronted with deadly reactive oxygen species (ROS). Withstanding ROS produced by the host innate immunity is an important strategy evolved by pathogenic Leptospira for persisting in and colonizing hosts. The peroxide stress regulator, PerR, represses genes involved in ROS defenses in L. interrogans. We have performed RNA sequencing in WT and perR mutant strains to characterize the L. interrogans adaptive response to hydrogen peroxide. We showed that Leptospira solicit three main peroxidase machineries (catalase, cytochrome C peroxidase and peroxiredoxin) and heme to adapt to peroxide stress as well as canonical chaperones of the heat shock response, and DNA repair. Determining the PerR regulon allowed to identify the PerR-dependent mechanisms of the peroxide adaptive response and has revealed a regulatory network involving other transcriptional regulators, two-component systems and sigma factors as well as non-coding RNAs that putatively orchestrate, in concert with PerR, this adaptive response. Our findings provide comprehensive insight into the mechanisms required by pathogenic Leptospira to overcome infection-related oxidants. This will participate in framing future hypothesis-driven studies to identify and decipher novel virulence mechanisms.

ORGANISM(S): Leptospira interrogans serovar Manilae

PROVIDER: GSE140019 | GEO | 2020/09/22

REPOSITORIES: GEO

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Interplay between two peroxide stress regulators in the oxidative stress response and virulence of pathogenic Leptospira

Project description:Pathogenic Leptospira spp. are the causative agents of the zoonotic disease leptospirosis. During infection, Leptospira are confronted with deadly reactive oxygen species (ROS). Withstanding ROS produced by the host innate immunity is an important strategy evolved by pathogenic Leptospira for persisting in and colonizing hosts. The peroxide stress regulator, PerRA, represses genes involved in ROS defenses in L. interrogans. We have identified an ORF encoding a putative second PerR in pathogenic Leptospira that we named PerRB. We have determined the transcriptomic profil of a single perRB and a double perRAperRB mutants. The concomitant inactivation of perRA and perRB has a pleiotropic effect on the transcriptomic profil of L. interrogans. The lack of both PerRA and PerRB regulators led to the differential expression of several virulence-associated genes and a loss of virulence. Our findings provide new insights into a new regulatory network that controls virulence and host colonization.

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Analysis of the human endothelial cell response to pathogenic Leptospira interrogans vs. non-pathogenic Leptospira biflexa (HMEC data)

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Analysis of the human endothelial cell response to pathogenic Leptospira interrogans vs. non-pathogenic Leptospira biflexa (Eahy1 data)

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Analysis of the human endothelial cell response to pathogenic Leptospira interrogans vs. non-pathogenic Leptospira biflexa (HMEC data)

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2010-07-27 | E-GEOD-23173 | biostudies-arrayexpress

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Bacillus Stress Responses

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Bacillus Stress Responses

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