Mycobacterium leprae

Mycobacterium leprae, also known as Hansen’s bacillus, is the bacterium that causes leprosy (Hansen's disease).^[1] It is an intracellular, pleomorphic, acid fast bacterium.^[2] M. leprae is a Gram-positive, aerobic rod-shaped (bacillus) 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 fuscin rather than with the traditional Gram stain. The culture takes several weeks to mature.

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Optical microscopy shows M. leprae in clumps, rounded masses, or in groups of bacilli side by side.

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 man. ^[3][4]

The organism has never been successfully grown on an artificial cell culture media.^[2] Instead it has been grown in mouse foot pads and more recently in nine-banded armadillos. This can be used as a diagnostic test for the presence of bacillus in body lesions of suspected leprosy patients. The bacterium can infect armadillos, so it is studied in them. The difficulty in culturing the organism appears to be due to the fact that the organism is an obligate intracellular parasite that lacks many necessary genes for independent survival. The complex and unique cell wall that makes members of the Mycobacterium genus 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.

M. leprae was sensitive to dapsone (diaminodiphenylsulfone, the first effective treatment which was discovered for leprosy in the 1940's), 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 that many symptoms of leprosy must be due in part to the presence of dead cells.

Mycobacterium leprae genome

Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory.^[5] Comparing the genome sequence of Mycobacterium leprae with that of Mycobacterium tuberculosis provides clear explanations for these properties and reveal 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. ^[6]

The genome sequence of a strain of M. leprae, originally isolated in Tamil Nadu and designated TN, has been completed recently. The sequence was obtained by a combined approach, employing automated DNA sequence analysis of selected cosmids and whole-genome 'shotgun' clones. After the finishing process, the genome sequence was found to contain 3,268,203 base pairs (bp), and to have an average G+C content of 57.8%, values much lower than the corresponding values for M. tuberculosis, which are 4, 441,529 bp and 65.6% G+C. There are 1500 genes which are common to both M. leprae and M. tuberculosis. The comparative analysis suggests that both mycobacteria derived from a common ancestor and, at one stage, had gene pools of similar size. Downsizing from a genome of 4.42 Mb, such as that of M. tuberculosis, to one of 3.27 Mb would account for the loss of some 1200 protein coding sequences. There is evidence that many of the genes that were present in the genome of M. leprae have truly been lost. ^[7]

Information from the completed genome can be useful to develop diagnostic skin tests, understanding the mechanism of nerve damage, drug resistance and to identify novel drug targets for rational design of new therapeutic regimens and drugs to treat leprosy and its complications.

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