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Shinnick, Thomas M.
Although Mycobacterium leprae was one of the first bacterial pathogens of humans to be described (Hansen, 1874), progress on understanding the basic biology and pathogenicity of this organism has been greatly hampered by the inability to find a conventional laboratory medium or tissue culture system that can support its growth. Consequently, the only means of propagating this organism at present is by using experimental animals. Furthermore, it has been found that the nine-banded armadillo can be used to produce large numbers of bacilli (Kirchheimer and Storrs, 1971; Storrs, 1971). Relatively little is known, therefore, about the taxonomy, genetics, and biochemistry of this species. A corollary of this is that much of what we do know about M. leprae has come from studies of the disease it causes (leprosy or Hansen's disease) and from the animal models. As such, this chapter emphasizes the characteristics and behavior of M. leprae in experimental animal model systems and in humans. Several excellent reviews on the clinical aspects, epidemiology, immunology, and pathology of leprosy and on the biochemistry and immunochemistry of M. leprae have been published recently, and the reader is referred to these for additional information (Bloom and Godal, 1983; Bloom and Mehra, 1984; Fine, 1982; Gaylord and Brennan, 1987; Hastings, 1986; Hastings and Franzblau, 1988; Jopling and McDougall, 1988; Kaplan and Cohn, 1986; Stewart-Tull, 1982).Although M. leprae can occasionally be found in the body extracellularly, the bacillis appears to be able to replicate only within cells of the host, most commonly in macrophages and Schwann cells (Bloom and Godal, 1983; Kaplan and Cohn, 1986). Hence, M. leprae is considered to be an obligate intracellular pathogen. In host cells, the bacilli are found singly or in clumps referred to as globi (Cowdry, 1940). The bacilli are straight or slightly curved, Gram-positive, acid-fast, alcohol-fast, nonmotile rods ranging from 1 to 8 µm in length and 0.2 to 0.5 µm in width (Draper, 1983). Acid- and alcohol-fastness refers to the ability of the bacillus to retain the color of certain dyes, usually carbol fuchsin, following treatment with mild acid and alcohol, respectively.M. leprae has been placed in the genus Mycobacterium in the family Actinomycetales based mainly on cell structure, staining properties and chemical composition as well as on the basis of the presence of mycolic acids, antigens characteristic of mycobacteria, and a lipid-rich cell envelope (Draper, 1976; Harboe et al., 1977; Stanford et al., 1975). For example, the M. leprae bacillus closely resembles M. tuberculosis bacilli in size, morphology, and staining characteristics, although it does stain a little more deeply with carbol fuchsin and the staining is somewhat less acid fast. Recently, analyses of the ribosomal RNA sequences of armadillo-grown M. leprae by nucleic acid hybridization techniques (Sela et al., 1989) and by ribosomal RNA sequence comparisons (Smida et al., 1988) revealed that M. leprae is closely related to the corynebacteria, nocardia, and mycobacteria, especially to the two slowly growing Mycobacterium species M. avium and M. tuberculosis. Although these observations indicate that M. leprae should be classified in the genus Mycobacterium, several features distinguish M. leprae from other members of the Mycobacterium genus. These are: 1) loss of acid-fastness upon extraction with pyridine, although M. smegmatis, M. vaccae, and M. phlei do lose acid fastness after prolonged exposure to pyridine (Fisher and Barksdale, 1971; McCormick and Sanchez, 1979; Skinsnes et al., 1975); 2) ability to oxidize 3,4-dihydroxyphenylalanine (Prabhakaran and Kirchheimer, 1966); 3) replacement of L-alanine with glycine in the linking peptide of peptidoglycan (Draper, 1976); 4) 56% GC content as compared with 65–70% for most Mycobacterium species (Clark-Curtiss et al., 1985; Imaeda et al., 1982; Wayne and Gross, 1968); and 5) lack of substantial genomic DNA homology with other Mycobacterium species (quite in contrast with the ribosomal rRNA results) (Athwal et al., 1984; Grosskinski et al., 1989). Although these differences are not sufficient to exclude M. leprae from the genus Mycobacterium, they are sufficient to render the final taxonomic position of M. leprae somewhat in doubt.