Mycobacterium leprae. A multifactorial approach

Evidence is accumulating that Mycobacterium leprae is probably a microbe­ dependent microbe. l O1 3 The first report that multiplication of M. leprae was promoted by a growth factor of mycobacterial origin was proposed by Twort l 9 in 1 9 1 0 , two years before the discovery of the cultivation of 'lohne's bacilli' in media enriched with heat-killed mycobacteria . 2o The growth factor was identified 37 years later as mycobactin .4 It became evident that mycobacteria necessitate two distinct iron transport compounds : exochelins for extracellular iron acquisition and mycobactins for cell-wall iron transport and intracellular iron storage . 1 4, 1 5 I n attempting in vitro cultivation o f M . leprae, the results of Twort l 9 remained unnoticed until Hanks6 adopted 'the mycobactin-requiring M. paratuberculosis as a model toward the cultivation of M. leprae' . When Ishaque and Kat07 reported the presence of a cytochrome system in M. leprae, iron was recognized as an essential element for M. leprae. Consequently, as for all mycobacteria, the iron transport compounds are integral mediators for the functioning of the iron­ dependent cytochromes, electron transport and energy metabolism of M. leprae. Hall, Wheeler & Ratledge5 have shown that exochelins from M. neoaurum mediate extracellular iron uptake into M. leprae . Due to methodological difficulties, it was not evident whether M. leprae could produce its own exochelins. M. leprae is, however, deficient in mycobactin, as reported by Kato . I I The above data, coupled with the ever-increasing number of reports on the cultivation of leprosy-derived mycobacteria from M. leprae-infected human and armadillo tissues, prompted Kato to propose that M. leprae was probably a microbe-dependent microorganism 1 0, 1 1 This concept (Table 1 ) implies that the cultivable leprosy-derived mycobacteria are an integral part of the pathology, by providing the iron transporting compounds for M. leprae. 1 01 3