Genetic features of Mycobacterium avium subsp. paratuberculosis strains circulating in the west of France deciphered by whole-genome sequencing

Authors: CONDE, CYRIL - Universite De Tours; THEZE, JULIEN - Clermont Universite, Universite D'Auvergne, Unite De Nutrition Humaine; COCHARD, THIERRY - Universite De Tours; ROSSIGNOL, MARIE-NOELLE - Université Paris-Saclay; FOURICHON, CHRISTINE - Inrae; DELAFOSSE, ARNAUD - Group Of Defense Sanitation(SANITARY DEFENSE GROUP); JOLY, ALAIN - Group Of Defense Sanitation(SANITARY DEFENSE GROUP); GUATTEO, RAPHAEL - Inrae; SCHIBLER, LAURENT - University Of Paris; Bannantine, John; BIET, FRANCK - Universite De Tours

Submitted to: Microbiology Spectrum
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/10/2022
Publication Date: 11/29/2022
Citation: Conde, C., Theze, J., Cochard, T., Rossignol, M., Fourichon, C., Delafosse, A., Joly, A., Guatteo, R., Schibler, L., Bannantine, J.P., Biet, F. 2022. Genetic features of Mycobacterium avium subsp. paratuberculosis strains circulating in the west of France deciphered by whole-genome sequencing. Microbiology Spectrum. https://doi.org/10.1128/spectrum.03392-22.
DOI: https://doi.org/10.1128/spectrum.03392-22

Interpretive Summary: An understanding of how the bacterial pathogen that causes Johne's disease spreads on the farm and through the herd is important to understanding transmission dynamics. With this knowledge, we can then inform management strategies as well as counter prominent modes of disease spread. In this study we examined over 150 genome sequences obtained from Mycobacterium avium subspecies paratuberculosis (Map), the bacterium that causes Johne's disease, isolated on farms in western France. We discovered that many cows had a clonal infection (meaning infected with a single strain of Map), while others had a mixed infection (multiple strains of Map infecting the same cow). We showed this not only at the animal level, but the herd level as well. We also were able to characterize the evolution of strains as a function of geographical distance from the farms. We conclude that Map does indeed spread farm to farm due to animal movements. These results are of interest to animal producers (especially dairy), stakeholders and researchers in the field.

Technical Abstract: Paratuberculosis is a chronic infection of the intestine, mainly the ileum, caused by Mycobacterium avium subsp. paratuberculosis (Map) in cattle and other ruminants. This enzootic disease is present worldwide and has a negative impact on the dairy cattle industry. For this subspecies, the current genotyping tools do not make it possible to investigate the genetic diversity of these closely-related strains. These limitations can be overcome by the application of Whole Genome Sequencing (WGS), particularly for clonal populations such as Map. WGS analyses can provide comprehensive genetic information, including information on genome evolution, discrimination of closely related strains and virulence determinants. The purpose of the present study was to undertake a whole-genome analysis of Map strains to identify accurate phylogenetic relationships between isolates and establish correlations between genomic traits and epidemiological data within a defined geographic location. A panel of 200 animal field strains were selected based on a previous large-scale longitudinal study representative of the Map population circulating in the West of France. Strains were isolated from Prim'Holstein or Normande dairy breeds naturally infected with Map. For each strain isolated, all information about the animal is available including: breed, herd prevalence, locations, serological status and Map excretion level. Pangenome analysis of this panel confirmed the degree of Map clonality. SNP analysis provided accurate phylogeny able to distinguish each strain divided into 4 clusters independently of the cattle breed. Legacy strains from 2003 were also sequenced and showed little change when comparing recent isolates. Interestingly, the phylogeny clearly distinguished the two major MLVA profiles. A phylogeny was inferred with French Map isolates and with other Map isolates found across the world. Relationships between genetic traits and epidemiological data can now be investigated to better understand the transmission dynamics of the disease.