Table 1.
Comparison of the three major pathogenic species within the Mycobacterium genus
| Features | M. tuberculosis a | M. leprae | M. ulcerans b |
|---|---|---|---|
| Genome | Genome of 4.4 Mb with 4000 genes and only six pseudogenes (91 % coding capacity) No evidence of major reductive evolution |
Reductive evolution and large pseudogene (1116) formation resulting in a 3.31-Mb genome Only 50 % coding capacity by 1605 genes |
M. ulcerans downsized from 6.6 MB (M. marinum) to 5.8 Mb genome M. marinum and M. ulcerans share 97 % of genes since they share a common ancestor and evolved from M. marinum by lateral gene transfer and reductive evolution (~771 pseudogenes) Selected genes facilitate occupying an aerobic niche environment, osmotically stable, dark, and extracellular environments |
| Target cell of infection |
Intracellular
Macrophages (alveolar) and in the reticuloendothelial system Non-classical immune cells (epithelial cells, endothelial cells, fibroblasts, adipocytes, glia and neurons) [70] |
Intracellular
Schwann cells Histiocytes Keratinocytes |
Extracellular
Extracellular matrix in subcutaneous tissues where M. ulcerans directs the production of the polyketide toxin mycolactonec leading to tissue necrosis and local tissue and systemic immunosuppression |
| Pathogenic mechanisms | Intracellular persistence in macrophages causes necrotizing granulomas that cause tissue destruction in the lung or other organs | Infection of Schwann cells leads to peripheral nerve dysfunction secondary to demyelination Reprogramming of Schwann cells linked to disseminated disease |
Destructive ulcerative ulcers (Buruli ulcer) with subcutaneous fat necrosis |
| Environmental determinants | Members of the Mycobacterium tuberculosis complex can be shed by infected hosts to the environment in sputum, feces, and urine by humans; in milk from dairy animals (cattle) and infected body tissues from other domestic and wild animals Free-living amoebas may act as macrophage-like niches in the environment |
Clustering of cases by geospatial assessments of thermal-hydrological determinants in Ethiopia and India Armadillo is a natural host in the Western Hemisphere and causes a zoonosis in the Southern USA In some settings some primates species may become reservoirs of M. leprae There is evidence of viable M. leprae found in soil, water, and free-living amoebas (Acanthamboeba spp.) Sphagnum and other moss vegetation may have facilitated transmission in the second half o the 19th and the beginning of the 20th century living in isolated farms in coastal Norway Ecological studies have linked contaminated water with M. leprae in polluted surface water in the tropics M. leprae contaminates clothes by washing in streams and incomplete drying in the humid tropical climate; or by bathing and washing clothes or dishes in a report from Indonesia In Brazil, bathing twice weekly, infrequent changing of bed linens or hammock among impoverished populations in Northern Brazil |
Mycobacterium ulcerans transmission cycle involves aquatic insect vectors, aquatic plants, and aquatic animals Aquatic plants (e.g., Rhizoclonium sp., H. reticulatum) favor the growth and biofilm production of M. ulcerans There are two different ways that M. ulcerans persists in the environment and infect aquatic animals (in the savanna landscape residing in stagnant or slowly moving waters; and in tropical rainforests dwelling in alkaline waters and its growth is dependent on climate changes) |
| Vector transmission | M. canettii the ancestor of M. tuberculosis complex (MTC) was probably transmitted by an unidentified ancestral vector (e.g., plant or insect) prior to the Neolithic revolution (>12,000 years ago)d | Some mosquitoese
(Culex fatigans and Cimex hemipterus caught in the field in an endemic area in India harbor viable M. leprae Laboratory-bred Culex fatigans and Cimex hempterus are able to take up leprosy bacilli from blood of patients with untreated lepromatous leprosy The feasibility of biting arthropods amplifying the transmission of leprosy through mechanical studies demonstrated that large numbers of bacilli are readily available to the biting apparatus of arthropods among individuals with untreated multibacillary leprosy Bacteremia in cases of leprosy may make viable bacilli available to biting arthropods |
Naucoridae (aquatic insects) in West African Countries (Ghana, Benin, Togo) |
| Effect of BCG (Bacille-Calmette-Guérin) | Protection for disseminated tuberculosis including tuberculous meningitis in children <4 years of age | Variable degree of protection from different reports | Offers important protection against Buruli ulcer |
Many mycobacterial species may cause skin and soft tissue infections including M. tuberculosis, M. leprae, M. ulcerans, M. marinum, M. hemophilus, M. kansasii, M. abscessus, M. fortuitum, and M. chelonei (Refs. [73])
a Mycobacterium tuberculosis complex consists of seven species capable of causing tuberculosis (M. canetti, M. pinnipedii, M. africae (subtypes Ia, Ib and II), M. microti, M. caprae, M. bovis, M. bovis BCG, Dassie bacillus)
b Mycobacterium marinum is a closely related species to M. ulcerans. Mycolatone is the toxin produced by M. ulcerans is responsible for causing cutaneous and subcutaneous ulceration (tissue necrosis) and associated local and systemic immunosuppression
cMycolactone produced inhibition of protein translocation into the endoplasmic reticulum resulting in a deficit release of innate immune system cytokines, membrane receptors, adhesion molecules, and specific immune system cytokines
dOf the Mycobacterium tuberculosis complex, M. bovis and M. caprae are found in hosts domesticated 10,000–12,000 years ago, earlier ancestral species infected humans many years before that era and subsequently spread to other hosts directly from humans or through an unknown vector
eThere are several biting arthropods residing in leprosy endemic areas of which any could potentially act as a vector for the transmission of leprosy