Mycobacterium bovis and you: A comprehensive look at the bacteria, its similarities to Mycobacterium tuberculosis, and its relationship with human disease

Abstract

While Mycobacterium tuberculosis is the primary cause of tuberculosis in people, multiple other mycobacteria are capable of doing so. With the World Health Organization's goal of a 90% reduction in tuberculosis by 2035, all tuberculous mycobacteria need to be addressed. Understanding not only the similarities, but importantly the differences between the different species is crucial if eradication is ever to be achieved. Mycobacterium bovis, while typically thought of as a disease of cattle, remains a possible source of human infection worldwide. Although this species' genome differs from Mycobacterium tuberculosis by only 0.05%, significant differences are present, creating unique challenges to address. This review focuses on features which distinguish this bacterium from Mycobacterium tuberculosis, including differences in origin, structure, environmental persistence, host preferences, infection and disease, host immune response, diagnostics and treatment.

Introduction

Human populations have been plagued by zoonotic diseases since their first divergence from the great evolutionary tree. When these groups transitioned from hunter-gatherers to farmers and began domesticating livestock, a sudden intimacy between species was forged. The perpetual interaction between man and beast allowed many of these diseases to flourish and carve out niches so adeptly, we are still battling their presence today. A prime example is that of tuberculosis, which made its debut an estimated 40,000–70,000 years ago [1,2]. Although typically thought of as being caused by Mycobacterium tuberculosis (M. tb), tuberculosis is not a disease defined by a single bacterium, but rather 12 closely related members of the Mycobacterium genus, termed the Mycobacterium tuberculosis complex (MTBC). Members include Mycobacteriaceae species: tuberculosis, bovis (M. bovis) canettii (M. canettii), africanum (M. africanum), microti (M. microti), pinnipedii (M. pinnipedii), orygis (M. orygis), caprae (M. caprae), mungi (M. mungi), suricattae (M. suricattae), and the Dassie and Chimpanzee bacilli [[2], [3], [4]]. All are gram-positive, aerobic, acid-fast bacilli (AFB) able to produce the quintessential and characteristic granuloma that ultimately defines tuberculosis. Each bacterium within the complex has the ability to infect >1 species of animal with the exception of M. mungi, M. surcattae, the Dassie bacillus and M. canettii which appear limited to banded mongooses (Mungos mungo), meerkats (Suricata suricatta), rock hyraxes (Procavia capensis), and humans respectively [[5], [6], [7], [8]]. Species affected include livestock and numerous wildlife species. Humans are susceptible in varying degrees to 8 of the 11 MTBC members, most notably M. tb, M. africanum, M. canettii and M. bovis. As a result of its diversity, tuberculosis claims numerous human and animals lives daily, and at a massive economic cost.

In 2017, there were an estimated 10 million new cases of tuberculosis with 1.6 million deaths [9]. While majority of these cases were due to M. tb, approximately 142,000 new cases and 12,500 deaths were due to M. bovis. Termed “zoonotic TB,” M. bovis cases in humans are likely underestimated due to lack of reporting in endemic countries and limited laboratory capacity [10,11]. From 2005 to 2010 M. bovis infected cattle herds were present in 109 countries [11]. As such, M. bovis remains a major public health threat. While low and lower middle income countries historically have a higher burden of M. bovis, other countries are not necessarily spared. The number of new human cases which occurred in 2018 is broken down by country and depicted in Fig. 1. As discussed later, M. bovis’ wide host range lends itself to finding a niche in even the highest income societies.

This review will closely examine M. bovis as it is one of the most prevalent and economically taxing species within the MTBC. While generally thought of as a disease of cattle, the information contained herein will instead focus on M. bovis’ intimate relationship with humans. It will compare M. bovis to M. tb as well as delve into differences in disease pathogenesis, immunologic response, diagnostics and treatment.