Mycobacterium avium

5.2.1 Discovery of Mycobacterium avium

Avian tuberculosis is a chronic wasting disease of wild and domesticated fowl that is difficult to detect in its early phase. Advanced disease is characterized by weight loss, fatigue, ataxia, reduced egg production and ultimately death (Feldman, 1938; Thorel et al., 199 7).

By using these criteria to classify isolates from tuberculous animals, it was discovered that infections due to M. avium were common in swine. It had long been recognized that avi­an tuberculosis was contagious among birds and now it appeared that this disease could be spread to hogs. Investigations revealed that afflicted swine had usually been in con­tact with sick birds and, in several cases, had actually consumed offal from infected fowl (Feldman, 1939). Mycobacterium avium was also isolated from diseased cattle, sheep, deer, marsupials and non-human primates.

‘Corresponding author: christine.y.turenne@gmail.com

© CAB International 2020. Paratuberculosis: Organism, Disease, Control, 2nd Edition

(eds M.A. Behr et al.)

Although considered relatively resistant, mice, rats, squirrels, dogs, goats and horses could be infected experimentally (Feldman, 1938; Thorel et al., 1997).

5.2.2 Mycobacterium avium and human disease

Despite the broad host range of M. avium, hu­mans seemed immune to infection. Between 1901 and 1911, the British Royal Commission on Tuberculosis conducted an extensive study to address the possibility of disease transmission between animals and humans. They concluded that M. bovis could be transmitted to humans via infected beef and milk. In contrast, the risk posed by M. avium-infected eggs and fowl ap­peared negligible (Miller, 1911). Even so, there continued to be sporadic reports of human disease caused by M. avium. Most publications were methodologically flawed and unconvinc­ing, but when Feldman conducted a critical review, he identified 13 probable cases, dating back to 1905 (Feldman, 1938). In another at­tempt to resolve this issue, Branch (1931) col­lected strains described in previous studies and subjected them to a uniform set of tests. After assessing both morphological and pathological characteristics, he determined that several iso­lates were genuine examples of M. avium and thus represented authentic cases of human infection. Of the remaining strains, some were typical of M. tuberculosis, whereas others did not conform to known types. Branch suggested that these atypical isolates represented novel acid­fast pathogens.

5.2.3 Mycobacterium paratuberculosis is a subspecies of Mycobacterium avium

DNA sequencing-based approaches are less subjective and more reproducible than tra­ditional classification schemes, but results can seem at odds with phenotypic observa­tions. Historically, the avian tubercle bacil­lus, the wood pigeon bacillus and the agent of Johne's disease were classified as separate species (McFadden et al., 1987; Saxegaard and Baess, 1988; Yoshimura and Graham, 1988). However, genetic analysis reveals extensive homology and current nomenclature identi­fies these organisms as subspecies of M. avium (Thorel et al., 1990).

Mycobacterium avium subsp. avium re­fers to the classic avian tubercle bacillus.

Although not officially validated, the des­ignation M. avium subsp. hominissuis is widely accepted and aims to distinguish human- and pig-derived strains from bird isolates (Mijs et al., 2002). Phylogenomic analysis of isolates from Asia, Europe and North America have revealed extensive diversity within M. avium hominissuis, including evidence for at least five distinct lineages (Uchiya et al., 2017; Yano et al., 2017). Additional studies are required to capture the true global diversity of M. avium hominissuis and elucidate the relationship be­tween strain genotype, phenotype and patho­genic potential.

MAP refers to the former Mycobacterium paratuberculosis or Mycobacterium johnei, the agent of paratuberculosis or Johne's disease. A thorough history of Johne's disease/para- tuberculosis has been provided elsewhere (see Manning and Collins, Chapter 1, previous edi­tion of this book), but it should be noted that in their initial description of ‘pseudo-tuberculous enteritis', Johne and Frothingham postulated that the avian tubercle bacillus was respon­sible. By use of multilocus sequence analysis, the phylogenetic relationships of all recognized M. avium subspecies were better established (Turenne et al., 2008). Out of the heterogene­ous mix of environmental and opportunistic strains represented by M. avium hominissuis emerge two independently evolved pathogenic clones (Fig. 5.1.). One of these comprised the

Fig.

avian subspecies (M. avium subsp. avium and M. avium subsp. silvaticum) whereas the other only included MAP strains, with separate phy­logenetic branches observed for the sheep (S) and cattle (C) lineages. The two major sublin­eages of MAP were subsequently confirmed by whole genome sequencing (WGS) of >140 strains (Bryant et al., 2016). The MAP-C group is traditionally associated with cattle strains, but encompasses isolates from diverse hosts, including goats, sheep, deer, bison and humans. Similarly, the MAP-S group, tradi­tionally associated with sheep strains, also in­cludes isolates from goats, deer and camels. For a thorough discussion of MAP genomics, see Chapter 6, this volume.

Although not formally considered a subspe­cies of M. avium at this time, genomic analysis has recently revealed that M. Iepraemurium, the agent of murine and feline leprosy, is very closely related to M. avium (van Ingen et al., 2018). It has been suggested that M. lepraemurium evolved through massive gene decay and reductive evo­lution from a M. avium-like ancestor (Benjak et al., 2017).

5.3