Transposable Prophages in Leptospira: An Ancient, Now Diverse, Group Predominant in Causative Agents of Weil's Disease.

Eric Olo Ndela,Ariane Toussaint,François Enault

doi:10.3390/ijms222413434

Abstract

The virome associated with the corkscrew shaped bacterium Leptospira, responsible for Weil’s disease, is scarcely known, and genetic tools available for these bacteria remain limited. To reduce these two issues, potential transposable prophages were searched in Leptospiraceae genomes. The 236 predicted transposable prophages were particularly abundant in the most pathogenic leptospiral clade, being potentially involved in the acquisition of virulent traits. According to genomic similarities and phylogenies, these prophages are distantly related to known transposable phages and are organized into six groups, one of them encompassing prophages with unusual TA-TA ends. Interestingly, structural and transposition proteins reconstruct different relationships between groups, suggesting ancestral recombinations. Based on the baseplate phylogeny, two large clades emerge, with specific gene-contents and high sequence divergence reflecting their ancient origin. Despite their high divergence, the size and overall genomic organization of all prophages are very conserved, a testimony to the highly constrained nature of their genomes. Finally, similarities between these prophages and the three known non-transposable phages infecting L. biflexa, suggest gene transfer between different Caudovirales inside their leptospiral host, and the possibility to use some of the transposable prophages in that model strain.

Highlights

In 1886, Adolf Weil (Ariane Toussaint’s great-grand father) first described what is known as leptospirosis, which he reported as an “acute infectious disease with enlargement of the spleen, jaundice, and nephritis” [1]
Existing prophage prediction algorithms do not reliably predict transposable prophages, often missing one or both ends. This is most likely due to the presence of a rather long, poorly conserved region, the SEE semi-essential region, coding for small proteins with uncharacterized functions. Many such prophages have been manually predicted in different types of bacteria, using similarity searches with four conserved proteins encoded by both phage Mu and B3: the transposase TnpA, the transposition target binding ATPase TnpB, the late regulator Mor/C, and the GemA protein of unknown function [19,22,23]
The primary goal of this study was to evaluate the existence of transposablephages that could be used to derive genetic tools for Leptospiraceae

Summary

Introduction

In 1886, Adolf Weil (Ariane Toussaint’s great-grand father) first described what is known as leptospirosis, which he reported as an “acute infectious disease with enlargement of the spleen, jaundice, and nephritis” [1] This global zoonotic disease currently causes more than 1 million severe cases and 60,000 deaths per year [2], and is associated with agriculture or industrial activities [3]. Improvement in isolation procedures and the advent of the genomic era resulted in the sequencing of more than 700 genomes of Leptospiraceae [8,9], allowing for a better understanding of the diversity and evolution of this bacterial family and of its variable virulence It was recently proposed [10] to organize the Leptospira genus in four clades, according to their pathogenic status and phylogeny: (i) a clade termed

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