Mathieu Picardeau

Website: https://research.pasteur.fr/en/team/biology-of-spirochetes/
ORCID: 0000-0002-5338-5579

Leptospirosis is a widespread zoonosis that is responsible for over one million severe cases and 60,000 fatalities per year worldwide. The “Biology of Spirochetes” unit covers both fundamental research on the agent of leptospirosis through the research group and applied sciences / public health activities within the French National Reference Center for Leptospirosis. Many key aspects of Leptospira, which belong to the phylum of Spirochetes, an evolutionarily and structurally unique group of bacteria, remain to be explored to increase our understanding of this atypical bacterium, but also to develop novel strategies for the diagnosis and intervention of this treatable and preventable zoonosis.

The unit has pioneered the field of Leptospira genetics and is a recognized leader in the study of virulence factors in Leptospira. In the last few years, our research team has made significant contributions to defining key mechanisms involved in pathogenesis. These include: (i) identification of virulence factors by comparative genomics between saprophytic and pathogenic strains and generation of knock-out mutants, (ii) characterization of the first transcriptome and sRNA landscape of the pathogen L. interrogans as well as regulatory factors involved in promoting the adaptation of L. interrogans to the host, (iii) identification of flagellar proteins that are essential for full motility and virulence, and (iv) characterization of the leptospiral adaptation to oxidative stress. In the last few years, our main objective was to identify and characterize bacterial determinants that promote mammalian host adaptation and enable leptospires to rapidly disseminate and establish infection.

Our project for the future is to identify and characterize bacterial determinants that promote mammalian host adaptation and enable leptospires to rapidly disseminate and establish infection. The unique nature of the bacterium should allow the uncovering of original mechanisms of bacterial motility and gene regulation. We will also continue our efforts, via the National Reference Center, to develop and improve diagnostic and typing tools to help in controling and preventing leptospirosis.

Top 5 publications

1- The oxidative stress response of pathogenic Leptospira is controlled by two peroxide stress regulators which putatively cooperate in controlling virulence.
Zavala-Alvarado C, G Huete S, Vincent AT, Sismeiro O, Legendre R, Varet H, Bussotti G, Lorioux C, Lechat P, Coppée JY, Veyrier FJ, Picardeau M, Benaroudj N. PLoS Pathog. 2021 Dec 2;17(12):e1009087. doi: 10.1371/journal.ppat.1009087. eCollection 2021 Dec. PMID: 34855911

2- Role of the major determinant of polar flagellation FlhG in the endoflagella-containing spirochete Leptospira.
Fule L, Halifa R, Fontana C, Sismeiro O, Legendre R, Varet H, Coppée JY, Murray GL, Adler B, Hendrixson DR, Buschiazzo A, Guo S, Liu J, Picardeau M. Mol Microbiol. 2021 Nov;116(5):1392-1406. doi: 10.1111/mmi.14831. Epub 2021 Oct 30. PMID: 34657338

3- Methylcytosine DNA modification is critical for global epigenetic regulation and virulence in the human pathogen Leptospira interrogans.
Gaultney RA, Vincent AT, Lorioux C, Coppée JY, Sismeiro O, Varet H, Legendre R, Cockram CA, Veyrier FJ, Picardeau M. Nucleic Acids Res. 2020 Dec 2;48(21):12102-12115. doi: 10.1093/nar/gkaa966. PMID: 33301041

4- Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics.
Vincent AT, Schiettekatte O, Goarant C, Neela VK, Bernet E, Thibeaux R, Ismail N, Mohd Khalid MKN, Amran F, Masuzawa T, Nakao R, Amara Korba A, Bourhy P, Veyrier FJ, Picardeau M. PLoS Negl Trop Dis. 2019 May 23;13(5):e0007270. doi: 10.1371/journal.pntd.0007270. eCollection 2019 May. PMID: 31120895

5- Genus-wide Leptospira core genome multilocus sequence typing for strain taxonomy and global surveillance.
Guglielmini J, Bourhy P, Schiettekatte O, Zinini F, Brisse S, Picardeau M. PLoS Negl Trop Dis. 2019 Apr 26;13(4):e0007374. doi: 10.1371/journal.pntd.0007374. eCollection 2019 Apr. PMID: 31026256

Dernières publications sur HAL :