Dr. Mathieu Picardeau - Unravelling the virulence factors and the endoflagellar system of the zoonotic spirochete Leptospira

Mathieu Picardeau

Unité Biologie des Spirochètes, Institut Pasteur, Paris, France

Unravelling the virulence factors and the endoflagellar system of the zoonotic spirochete Leptospira

It is estimated that one million patients suffer severe leptospirosis each year with nearly 60,000 deaths, mostly in developing tropical countries. Leptospirosis is one of the most highly neglected diseases, because it affects mostly marginalized populations in poor countries, but also because leptospires are difficult to culture and genetically intractable bacteria. Leptospires are ubiquitous bacteria found as free-living saprophytes or as pathogens that have evolved to infect a particularly broad range of hosts.

Our recent genomic study has shown that Leptospira is a highly heterogeneous bacterial genus. In particular, we have shown that a group of species, including L. interrogans, that are associated with the most severe infections in humans diverged after a specific node of evolution. I will present what has been learned about the virulence factors using comparative genomics.

Our group and others have shown that the success of spirochetes as pathogens is explained by their spiraled shape and endoflagellar motility, which enable these bacteria to cross connective tissues and barriers very efficiently and swiftly, contributing to escape the host immune system. I will discuss our recent findings showing that the supercoiled flagellar filaments, which are confined in the periplasmic space, comprise core and sheath proteins often present in several different isoforms each to assemble a very complex and asymmetric filament structure. We hypothesize that the filament’s inherent asymmetry and curvature play a key role in motility.

References

• Gibson et al. An asymmetric sheath controls flagellar supercoiling and motility in the leptospira spirochete. Elife 2020
• Vincent et al. Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Negl Trop Dis 2019