Mycobacterium leprae

Mycobacterium leprae, also known as Hansen’s bacillus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy. It is an intracellular, pleomorphic, acid-fast, pathogenic bacterium. M. leprae is an aerobic bacillus (rod-shaped bacterium) surrounded by the characteristic waxy coating unique to mycobacteria. In size and shape, it closely resembles Mycobacterium tuberculosis. Due to its thick waxy coating, M. leprae stains with a carbol fuchsin rather than with the traditional Gram stain. The culture takes several weeks to mature. Optical microscopy shows M. leprae in clumps, rounded masses, or in groups of bacilli side by side, and ranging from 1–8 μm in length and 0.2–0.5 μm in diameter. It was discovered in 1873 by the Norwegian physician Gerhard Armauer Hansen, who was searching for the bacteria in the skin nodules of patients with leprosy. It was the first bacterium to be identified as causing disease in humans. The organism has been successfully grown on an artificial cell culture medium on a very limited basis by researcher Arvind Dhople. Since in vitro cultivation is not generally possible, it has instead been grown in mouse foot pads and more recently in nine-banded armadillos because they, like humans, are susceptible to leprosy. Armadillos have a much lower body temperature than most mammals, and the bacteria are often found in their lungs, liver, and spleen. This can be used as a diagnostic test for the presence of bacilli in body lesions of suspected leprosy patients. The difficulty in culturing the organism appears to be because it is an obligate intracellular parasite that lacks many necessary genes for independent survival. The complex and unique cell wall that makes members of the genus Mycobacterium difficult to destroy is apparently also the reason for the extremely slow replication rate. Virulence factors include a waxy exterior coating, formed by the production of mycolic acids unique to Mycobacterium. Mycobacterium leprae was sensitive to dapsone (diaminodiphenylsulfone, the first effective treatment which was discovered for leprosy in the 1940s), but resistance against this antibiotic has developed over time. Therapy with dapsone alone is now strongly contraindicated. Currently, a multidrug treatment (MDT) is recommended by the World Health Organization, including dapsone, rifampicin. and clofazimine. In patients receiving the MDT, a high proportion of the bacilli die within a short amount of time without immediate relief of symptoms. This suggests many symptoms of leprosy must be due in part to the presence of dead cells. The incubation period of M. leprae can range between 9 months and 20 years. It replicates intracellularly inside histiocytes and nerve cells and has two forms. One form is 'tuberculoid,' which induces a cell-mediated response that limits its growth. Through this form, M. leprae multiplies at the site of entry, usually the skin, invading and colonizing Schwann cells. The microbe then induces T-helper lymphocytes, epitheloid cells, and giant cell infiltration of the skin, causing infected individuals to exhibit large flattened patches with raised and elevated red edges on their skin. These patches have dry, pale, hairless centers, accompanied by a loss of sensation on the skin. The loss of sensation may develop as a result of invasion of the peripheral sensory nerves. The macule at the cutaneous site of entry and the loss of pain sensation are key clinical indications that an individual has a tuberculoid form of leprosy. The second form of leprosy is the 'lepromatous' form, in which the microbes proliferate within the macrophages at the site of entry. They also grow within the epithelial tissues of the face and ear lobes. The suppressor T-cells that are induced are numerous, but the epithelioid and giant cells are rare or absent. With cell-mediated immunity impaired, large numbers of M. leprae appear in the macrophages and the infected patients develop papules at the entry site, marked by a folding of the skin. Gradual destruction of cutaneous nerves lead to what is referred to as 'classic lion face.' Extensive penetration of this microbe may lead to severe body damage; for example the loss of bones, fingers, and toes. M. leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the genome sequence of M. leprae with that of M. tuberculosis provides clear explanations for these properties, and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes. Gene deletion and decay appear to have eliminated many important metabolic activities, including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.