Reporter Mycobacterium

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

The antimicrobial activity of thiosemicarbazones against Mycobacterium tuberculosis in vitro was first reported by Domagk et al. [28] and later confirmed in vivo [29]. Screening revealed that only certain substituted be-nzaldehyde and heterocyclic thiosemicarbazones possess antitubercular activity [30-32]. The most widely used is p-acetamidobenzaldehyde thiosemicarbazone (trivial name = thiacetazone), 1. 

As discussed in the previous section, long-standing inflammation may result in accumulation of iron in the reticuloendothelial system. In HIV-1 infection, a good example of a prolonged inflammatory process, such an excessive deposition of iron has been documented, and it may be responsible for an enhanced risk of certain infections (Boelaert etal., 1996). For instance, two studies reported an increased risk of Mycobacterium avium infection when such an excess of iron was present, as histologically documented (A1 Khafaie et ah, 1997 De Monye et ah, 1999). 

The data reported identifies sulfur substrates tested for growth as sole sulfur source for the various strains. The strains may metabolize other sulfur compounds (not listed). A complete name of listed strains in Table 3 comprises Rhodococcus sp. SY1 Rhodococ-cus sp. H-2 Rhodococcus sp. D-l Rhodococcus ECRD-1 Gordona CYKS1 Nocar-dia sp. CYKS2 Paenibacillus All-2 Mycobacterium sp. WU-F1 Mycobacterium sp. WU-0103 Mycobacterium phlei sp. GTIS10 and Agrobacterium MC501. 

The second Mycobacterium strain capable of DBT desulfurization was M. phlei WU-F1 [30], This strain was also reported to desulfurize naphtho[2,l-b]thiophene (NTH) and 2-ethyl-NTH to sulfur free products with the following intermediates for the latter molecule 2-ethyl-NTH sulfoxide, l-(2 -hydroxynaphthyl)-l-butene, and l-naphthyl-2-hydroxy-1-butene [94], Thus, this organism was reported to consist of a sulfur-specific pathway capable of desulfurization of broad range of sulfur compounds including symmetric and asymmetric molecules. 

In addition to the strain X7B, several other Mycobacterium strains described in subsection (a. iv) of Section 2.2.3 have been reported to be capable of conversion of BT derivatives. A comparison on the activity of various strains is summarized in Table 5. 

Recently, several thermophilic organisms have been reported to be capable of sulfur-specific biodesulfurization. These include the Paenibacillus [87,151], Mycobacterium [30,31,85,94,294,295], etc. The ability to desulfurize sulfur compounds other than DBT derivatives, including benzothiophene, naphthothiophene, and benzonaphthothio-phene derivatives has also been demonstrated, thus widening the substrate specificity of the biodesulfurization process. Second, the thermophilic ability of the organisms offers temperature and operational advantages to further improve the commercialization potential of the BDS process. 

Several species of the genus Pseudomonas have been isolated that degrade carbazole and its alkyl derivatives and a variety of other microorganisms have been reported to mineralize non-basic nitrogen compounds, including species of Bacillus, Xanthomonas, Burkholderia, Comamonas, Beijerinckia, Mycobacterium, and Serratia [310],... 

Two patents were awarded on microbial desulfurization of sulfur-containing heterocyclic compound [155,156], the first targeting DBT and alkylated DBTs and the other benzothiophenes and alkylated benzothiophenes. In both cases, the selective cleavage of the C—S bonds is reported as the main mechanism. The claimed bacteria strains are Mycobacterium G3 strain (PERM P-16105) and R. erythropolis KA2-5-1 strain (PERM P-16277), respectively. Special emphasis was made to the desulfurization of the recalcitrant 4,6-dimethyl-dibenzothiophene. The main product from DBT... 

Fietta A, Cascina A, Meloni F, Morosini M, Casali L, Bono L, Minoli L, Marone P A 10-year survey of Mycobacterium tuberculosis isolates in Pavia and their drug resistance A comparison with other Italian reports. J Chemother 2002 14 33-40. 

Spiess et al. (1998) reported that the Mycobacterium sp. Strain HL 4-NT-l utilized 4-nitrophenol as a sole source of nitrogen, carbon, and energy. Under anaerobic conditions, 4-nitrophenol completely degraded to 6-amino-3-methylphenol via the intermediate 4-hydroxyaminotoluene. Under aerobic conditions, 4-nitrophenol degraded slightly releasing small amounts of ammonia. 

In 1991, McChesney and El-Feraly described the isolation and structural elucidation of 3-formyl-6-methoxycarbazole (97) from the roots of C. lansium (23). The roots of this ornamental tree are used in traditional medicine in Taiwan to treat bronchitis and malaria (23). In 2005, Franzblau et al. isolated the same natural product from the stem bark of Micromelum hirsutum (103). They reported that 3-formyl-6-methoxycarbazole (97) shows in vitro anti-TB activity against the H37RV strain of Mycobacterium tuberculosis. 

In 2003, Sunthitikawinsakul et al. described the anti-mycobacterial activity of various 3-methylcarbazole derivatives, including 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), clausine K (clauszoline-J) (51) (see Scheme 2.11), and 7-methoxymukonal (68) (see Scheme 2.14) against Mycobacterium tuberculosis H37Ra. Except for clausine K (clauszoline-J) (51), all of these alkaloids also showed anti-fungal activity against Candida albicans (442). In 2005, Eranzblau et al. reported the in vitro anti-TB activity of various carbazole derivatives such as 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), lansine... 

Increasingly the existence of multiresistant strains is reported, especially in the United States but also elsewhere. Also the occurrence of infections with difficult to treat, so called atypical mycobacteria like Mycobacterium avium intracellulare and Mycobacterium kansasii is on the rise. These infections are especially seen in patients with a compromised immune system. In vitro these atypical mycobacteria often show resistance against first-choice drugs. However this in vitro lack of sensitivity does not always correspond with in vivo responses. 

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. 

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