# A Porcine-Isolated Mycobacterium bovis Strain Exhibits Hypervirulence in a Murine Pulmonary Tuberculosis Model

## TL;DR

A pig-isolated strain of Mycobacterium bovis shows higher virulence than a known virulent strain in a mouse model of tuberculosis.

## Contribution

Identification of a hypervirulent M. bovis strain from pigs and its distinct genomic and pathogenic features.

## Key findings

- MB894 caused more severe disease and higher organ colonization than MB303 in mice.
- Genomic analysis revealed candidate genes potentially linked to MB894's hypervirulence.
- MB894 induced higher cytokine levels and greater dissemination compared to MB303.

## Abstract

This study provides valuable insights into the pathogenic characteristics and immune response associated with Mycobacterium bovis strains, particularly focusing on a strain isolated from domestic pigs in Argentina. The research compares the local strain M. bovis strain 894 (MB894) with the highly virulent M. bovis MB303 strain from wild boar, contributing to understanding how M. bovis adapts and exhibits varying levels of virulence in different contexts. We used a murine infection model that allowed us to comprehensively evaluate several parameters critical to understanding the strain’s pathogenicity and performed whole genome sequencing to identify candidate genes that could explain the molecular mechanisms underlying the virulence of the strain. Further studies are needed to explore the virulence factors identified through genomic analysis.

Mycobacterium bovis is the causative agent of tuberculosis (TB) infecting a wide range of animal hosts, including humans. Domestic pigs (Sus scrofa domestica) are susceptible to different mycobacteria, particularly species within the Mycobacterium avium complex (MAC). However, in countries where bovine TB is endemic, such as Argentina, M. bovis is the most frequently reported species in pigs. This study aimed to evaluate the immune response and disease progression of a local strain (MB894) isolated from pigs and compare its pathogenicity with the highly virulent strain MB303, isolated from wild boar. Additionally, we sought to explore the genomic basis underlying the virulent phenotype of MB894. For this purpose, a murine infection model was used to assess pathogenicity, organ colonization, dissemination and cytokine induction. Whole-genome sequencing was performed to identify genetic features, including non-synonymous SNPs and INDELs, potentially associated with virulence. The severe immunopathogenesis produced by MB894, the higher multiplication rate in the evaluated organs, and the greater dissemination to other organs compared to MB303, combined with the cytokine levels induced by this strain, prompted us to classify MB894 as a hypervirulent strain. Genomic analysis revealed candidate genes that may be virulence factors contributing to this phenotype. In summary, MB894 represents a hypervirulent M. bovis strain with distinct pathogenic and genomic characteristics. These findings provide insights into the molecular determinants of virulence and highlight the need for further evaluation of identified gene candidates.