WorldCat Identities

Lambert, Ambroise (1986-....).

Works: 2 works in 3 publications in 1 language and 3 library holdings
Roles: Author, Opponent
Publication Timeline
Most widely held works by Ambroise Lambert
Etude de la motilité et du chimiotactisme chez les leptospires by Ambroise Lambert( Book )

2 editions published in 2014 in French and held by 2 WorldCat member libraries worldwide

Leptospira interrogans is the causative agent of leptospirosis, a zoonotic disease contracted through contact of an abraded skin with contaminated soil or water. Leptospires have a single flagellum inserted sub terminally at each pole, wrapping around the protoplasmic cylinder and extending towards the middle of the cell without overlapping . Chemotaxis is defined by the movement of an organism toward or away from a chemical compound. Attractants induce a movement toward themself and repellents induce a movement away from themself. I developed a capillary tube assay combined with real-time PCR. This strategy led to the characterization of several new chemoattractants of Leptospira spp.. We also showed significant differences in the chemotactic behaviour between pathogenic strain and the aquicole non pathogenic strain . Inactivation of an operon containing the two leptospiralfiaA genes had no effect on sheath morphology. However, further analysis of the flagellum confirmed that mutants lacking both FlaA proteins had an altered helicity, whereas the Wild-Type flagellum that is coiled . In addition I showed by scanning electron microscopy that this mutant lacked his hook shaped ends morphology confirming also that the flagellar coil is involved in cell ends morphology. Animal experimentations using both gerbil and hamster as acute model of leptospirosis showed that mutant lacking both FIaA proteins that was not able to translate failed to colonize target organs like kidney or liver and did not cause death while Wild-Type strain and the other mutant killed ail animais. Additionally, I explored chemotaxis involvement in the pathogenesis caused by L. interrogans which had not been previously studied. Our findings suggest for the first time that chemotaxis regulatory system might be involved in assymetrical coordination of flagellar motor and virulence of L. interrogans which was consistent with the previous findings obtained during my doctoral experience indicating that motility was involved in virulence. Finally, these data set the basis for the comprehensive analysis of the motility regulatory mechanisms and their function in Leptospira spp. physiology
Role of PerR regulators in oxidative stress response and virulence of pathogenic leptospira by Jose Crispin Zavala-Alvarado( )

1 edition published in 2019 in French and held by 1 WorldCat member library worldwide

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. More than one million cases of leptospirosis are currently reported annually in the world, with 10% of mortality. Clinical manifestations of this infection range from a febrile state to a severe life-threatening form characterized by multiple organ hemorrhages. However, these symptoms are not specific of leptospirosis, and they render this disease often underdiagnosed. When infecting host, Leptospira are confronted with dramatic adverse environmental changes such as deadly reactive oxygen species (ROS). Withstanding ROS produced by the host cells is a vital strategy evolved by pathogenic Leptospira for persisting in and colonizing hosts. In Leptospira, genes encoding defenses against ROS are under the control of a Peroxide stress Regulator (PerR1), a metalloprotein from the Fur (Ferric uptake regulator) family. One aim of this PhD was to identify the cellular factors solicited by pathogenic Leptospira to adapt to hydrogen peroxide and to determine the contribution of PerR1 in this adaptive response. We have obtained the transcriptome of L. interrogans cells exposed to H2O2.shown that three main peroxidase machinaries (catalase, cytochrome C peroxidase and peroxiredoxin) constitute the first line of defense against H2O2. In addition, canonical chaperones and DNA repair proteins are solicited to prevent and recover from oxidative damage. We have determined the PerR1 regulon and have demonstrated that not all members of the peroxide stimulon are under the control of PerR1. In fact, our study has revelead a regulatory network involving other transcriptional regulators, two-component systems and sigma factors as well as non-coding RNAs that could orchestrate, in cocert with PerR1, this adaptive response. Interestingly, our study has allowed the identification of PerR1-regulated genes encoding a TonB-dependent transport system, a lipoprotein (Lipl48) and a two-component system (VicKR) involved in Leptospira tolerance to superoxide. These factors could represent the first ever identified defense mechanisms against superoxide in L.interrogans, a bacterium lacking canonical superoxide dismutase. By examining the genome of L. interrogans, we identified a second putative PerR (PerR2) specific to the Leptospira pathogenic clade. Another aim of this thesis was to delineate the function of PerR2 and explore its interplay with PerR1 in the Leptospira oxidative stress response and virulence. Comparing the PerR1 and PerR2 regulons suggested that these two regulators do not have a redundant function during oxidative stress response in L. interrogans. Inactivating perR1 in L.interogans leads to an increased tolerance to hydrogen peroxide whereas inactivating perR2 leads to a higher resistance to superoxide; this difference in fitness is consistent with a disctinct function in oxidative stress adaptation. Concomitant inactivation of perR1 and perR2 leads to a higher ability to resist both peroxide and superoxide but, surprisingly, this double perR1perR2 mutant has an attenuated virulence and its ability to infect macrophages was impaired. Interestingly, the transcriptome of the double perR1perR2 mutant exhibited deregulation in several genes associated with Leptospira virulence. Altogether, our study has uncovered the complex regulatory network of the adaptive response to ROS in Leptospira and revealed the interplay between the PerR1 and PerR2, necessary for the defense against ROS and virulence in pathogenic Leptospira
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Alternative Names
Ambroise Lambert wetenschapper

French (3)