Mycobacterium leprae

Compounds closely related to the sulfonamide antibiotics proved to be the first drugs effective against Mycobacterium leprae, the causative agent of the disease known since antiquity, leprosy. These drugs are at least partly responsible for the decline of I hose horror spots, the leper colonies. 

Lepage S et al (1997) Dual multimodular class A penicillin-binding proteins in Mycobacterium leprae. J Bacteriol 179 4627 1630... 

Leprosy, also referred to as Hansen s disease, is caused by the bacterium Mycobacterium leprae. Although rare in colder climates, this disease may be seen in tropical and subtropical zones. Dapsone and clofazimine (Lamprene) are the two drags currently used to treat leprosy. The leprostatic drugs are listed in the Summaiy Drug Table Leprostatic Dragp. 

Since the causative organism of leprosy, one of the world s six major diseases, Mycobacterium leprae, is closely related to Mycobacterium tuberculosis, thio-semicarbazones have also been used as second-line drugs in the chemotherapy of leprosy [38]. The most widely used in leprosy treatment has been thiacetazone, and structure-activity relationships for it are similar to those observed for antitubercular thiosemicarbazones [39, 40]. 

Preparative TLC of crude Mycobacterium leprae lipids determination of the molecular 68... 

Assehneau, C. Clavel, S. Clement,F. Daffe, M. David, H. Laneelle, M. A. Prome, J. C. Lipid constituents of Mycobacterium leprae isolated from experimentally infected armadillo. Anna . Microbiol. (Paris) 1981,132A, 19-30. 

Additional studies illustrate that IFN-y stimulates phagocytic activity in humans suffering from various cancers, AIDS and lepromatous leprosy (leprosy is caused by the bacterium Mycobacterium leprae. Lepromatous leprosy is a severe contagious form of the disease leading to disfigurement). IFN-y may thus prove useful in treating such conditions. 

The lepromatous form of leprosy is characterized by loss ofcutaneoussensibility. Hansen sbacillus(Mycobacterium leprae), which proliferates only in environments cooler than the core temperature maintained by most mammals, is capable of infecting Schwann cells in subcutaneous nerves because the basal lamina of these cells contains a-dystroglycan, to which this mycobacterium binds, and because subcutaneous nerves are often cooler than deeper tissues. Lepromatous neuropathy is a common cause of sensory mononeuropathy multiplex in the developing World [16,17]. 

Rambukkana, A., Yamada, H., Zanazzi, G. et al. Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae. Science 282 2076-2070,1998. 

Rifampicin is highly active against Mycobacterium tuberculosis. Among atypical mycobacteria, it is active against Mycobacterium kansasii, Mycobacterium marinum, and most types of Mycobacterium scrofulaceum and Mycobacterium xenopi. Sensitivity of other mycobacteria varies. Rifampicin also exhibits activity against Mycobacterium leprae. 

Ethionamide is active with respect to Mycobacterium tuberculosis and Mycobacterium leprae, but it does not have an effect on other microorganisms. It enhances phagocytosis at the center of tuberculous inflammation, which facilitates its decomposition. However, it frequently causes side effects associated with the gastrointestinal tract as well as a hepa-totoxic effect in approximately 5% of patients. Synonyms of this drug are trecatil, ethimide, thiomid, tuberin, tuberoid, and others. 

Dapsone, which was first proposed in 1941, possesses both bactericidal as weU as bacteriostatic activity with respect to Mycobacterium leprae and Mycobacterium tuberculosis. It is used to treat patients with herpetiform dermatitis. It is believed that the mechanism of its action consists of competitive inhibition of the enzyme dihydroprotease synthetase, which blocks synthesis of folic acid in microorganisms, allowing it to also be viewed as an analog of p-aminobenzoic acid. Synonyms of this drug are avosulfon, croysulfon and others. 

Rifampicin (see Section III.a.2) has bactericidal activity against Mycobacterium lepra and is employed in combination with clofazamine and dapsone. 

Leprosy. A slowly progressive, chronic infectious disease caused by Mycobacterium leprae and characterized by the development of granulomatous or neurotropic lesions in the skin, mucous membranes, nerves, bones, and viscera. 

Leprosy is caused by Mycobacterium leprae. The various drugs used in the treatment of leprosy are classified as in table 9.12.1. 

PABA) incorporation into folic acid (inhibition of folate synthesis). In large proportion of Mycobacterium leprae infections e.g. in lepromatous leprosy, resistance can develop, so combination of dapsone, rifampicin and clofazimine is used in initial therapy. 

Mycobacterium leprae has never been grown in vitro, but animal models, such as growth in injected mouse footpads, have permitted laboratory evaluation of drugs. Only those drugs that have the widest clinical use are presented here. Because of increasing reports of dapsone resistance, treatment of leprosy with combinations of the drugs listed below is recommended. 

Gigg J, Gigg R, Payne S, Conant R (1986) Synthetic studies on the major serologically active glycolipid from Mycobacterium leprae, in Klein RA, Schmitz B (eds) Topics in lipid research — from structural elucidation to biological function, Royal Society of Chemistry p. 119... 

---