Hansen's Disease (Leprosy)

Current and Future Pharmacotherapy and Treatment of Disease-related Immunologic Reactions

Davey P. Legendre, Pharm.D.; Christina A. Muzny, M.D.; Edwin Swiatlo, M.D., Ph.D.

Disclosures

Pharmacotherapy. 2012;32(1):27-37. 

In This Article

Microbiology

Although M. leprae cannot be cultured in synthetic laboratory media, it does infect nine-banded armadillos and multiplies in mouse footpads. These animal hosts have provided sufficient quantities of bacteria for microbiologic investigations. The organism is an aerobic rod-shaped bacterium that is acid fast with carbol fuchsin and other commonly used bacterial stains.

The cell wall of M. leprae is structurally similar to that of most Mycobacterium species. The polymers that lie adjacent to the cytoplasmic membrane comprise a complex amalgam of polysaccharides and glycolipids. Mycolic acids constitute up to 60% of the cell wall by weight and are thought to be primarily responsible for the acid-fast staining characteristic of mycobacteria. The outer surface of the cell wall contains surface-exposed proteins that are unique to each species. The complex mixture of polysaccharides and glycolipids renders mycobacterial cells impermeable to most solutes without specific transport mechanisms. Resistance to both cellular and humoral immune responses is attributed, in large part, to the complex cell wall of pathogenic mycobacteria.[13]

Little is known about the physiology of M. leprae, but its doubling time of nearly 14 days in vivo is the longest of any known pathogen. The complete genome of a strain of M. leprae isolated in the Indian state of Tamil Nadu has been published.[14] The genome is ~3.2 Mbp and has a G + C content of 57.8%, compared with a G + C content of 65.6% in Mycobacterium tuberculosis. Although M. leprae and M. tuberculosis appear to have originated from a common ancestor, the M. leprae genome is ~30% smaller and contains over 1000 pseudogenes that have functional full-length homologues in M. tuberculosis. It appears that less than half the genome of M. leprae is protein-coding sequence. Many metabolic pathways found in other Mycobacterium species, including respiratory electron transport systems, are lacking in M. leprae, and its ability to generate energy in the form of adenosine triphosphate (ATP) is severely compromised.[14]

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