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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the in vitro activation of chicken gamma delta T cells. Both splenic alpha beta and gamma delta T cells obtained from complete Freund's adjuvant-primed chickens proliferated in vitro when stimulated with mycobacterial sonicate or purified protein derivative of Mycobacterium tuberculosis. When CD4+ cells or alpha beta T cell receptor (TcR)-positive cells were removed, both the proliferation and the blast formation of gamma delta T cells in response to mycobacterial antigens were abrogated. The response was restored if supernatant from concanavalin A (Con A)-activated lymphocyte cultures (CAS) as a source of helper factors was added together with the specific antigen purified protein derivative. The CD4- or alpha beta TcR-depleted cells still proliferated in response to Con A, although a decrease of the response was observed. To analyze the gamma delta T cell response more specifically we stimulated peripheral blood cells with immobilized monoclonal antibodies against T cell receptor. Anti-gamma delta TcR antibody alone did not induce significant proliferation. When CAS was added together with the anti-gamma delta TcR monoclonal antibody, a strong proliferation of gamma delta T cells was observed. In contrast, both V beta 1- and V beta 2-expressing alpha beta T cells proliferated in vitro in response to stimulation with the relevant anti-TcR monoclonal antibody alone. Depletion of either V beta 1+ or V beta 2+ T cell subset alone had no negative effect on the proliferation or blast formation of gamma delta T cells stimulated with mycobacterial antigens. Taken together our results suggest that CD4+ alpha beta T cells (both V beta 1- and V beta 2-expressing) play a role in the activation and response of chicken gamma delta T cells.
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PMID:Helper activity of CD4+ alpha beta T cells is required for the avian gamma delta T cell response. 834 71

Many strains of mycobacteria produce two ferric chelating substances that are termed exochelin (an excreted product) and mycobactin (a cell-associated product). These agents may function as iron acquisition siderophores. To examine the genetics of the iron acquisition system in mycobacteria, ultraviolet (UV) and transposon (Tn611) mutagenesis techniques were used to generate exochelin-deficient mutants of Mycobacterium smegmatis strains ATCC 607 and LR222 respectively. Mutants were identified on CAS siderophore detection agar plates. Comparisons of the amounts of CAS-reactive material excreted by the possible mutant strains with that of the wild-type strains verified that seven UV mutant strains and two confirmed transposition mutant strains were deficient in exochelin production. Cell-associated mycobactin production in the mutants appeared to be normal. From the two transposon mutants, the mutated gene regions were cloned and identified by colony hybridization with an IS6100 probe, and the DNA regions flanking the transposon insertion sites were then used as probes to clone the wild-type loci from M. smegmatis LR222 genomic DNA. Complementation assays showed that an 8 kb PstI fragment and a 4.8 kb PstI/SacI subclone of this fragment complemented one transposon mutant (LUN2) and one UV mutant (R92). A 10.1 kb SacI fragment restored exochelin production to the other transposon mutant (LUN1). The nucleotide sequence of the 15.3 kb DNA region that spanned the two transposon insertion sites overlapped the 5' region of the previously reported exochelin biosynthetic gene fxbA and contained three open reading frames that were transcribed in the opposite orientation to fxbA. The corresponding genes were designated exiT, fxbB and fxbC. The deduced amino acid sequence of ExiT suggested that it was a member of the ABC transporter superfamily, while FxbB and FxbC displayed significant homology with many enzymes (including pristinamycin I synthetase) that catalyse non-ribosomal peptide synthesis. We propose that the peptide backbone of the siderophore exochelin is synthesized in part by enzymes resembling non-ribosomal peptide synthetases and that the ABC transporter ExiT is responsible for exochelin excretion.
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PMID:Exochelin genes in Mycobacterium smegmatis: identification of an ABC transporter and two non-ribosomal peptide synthetase genes. 972 Aug 78

The antimicrobial effects of a new dihydrofolate reductase inhibitor, K-130 (2,4-diaminodiphenyl sulfone substituted 2,4-diamino-5-benzylpyrimidine), alone and in combination with dapsone (CAS 80-08-0) against both dapsone-sensitive and dapsone-resistant strains of Mycobacterium leprae were evaluated in vitro, in cell-free culture system, and in vivo, in mouse foot pads. The minimal inhibitory concentration of K-130 against dapsone-sensitive as well as dapsone resistant strains of M, leprae was 0.03 microgram/ml, and the activity was bactericidal in both cases. However, when combined with dapsone, K-130 exhibited synergism in case of dapsone-sensitive M. leprae, while in case of dapsone-resistant M. leprae, the effect was merely additive. Similar synergistic effects were also observed in the mouse foot pad system for both types of M. leprae strains.
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PMID:In vitro and in vivo activity of K-130, a dihydrofolate reductase inhibitor, against Mycobacterium leprae. 1021 72

The antibacterial effects of a new benzoxazinorifamycin, KRM-1648 (3'-hydroxy-5'-(4-isobutyl-1-piperazinyl, CAS 129791-92-0), against Mycobacterium ulcerans were evaluated in vivo in mouse foot pads, and the results were compared against those obtained with rifampicin (rifampin, CAS 13292-46-1). When mice were fed with the drugs from the day of footpad inoculations, KRM-1648, at concentrations of 0.001% and higher, mixed in mouse food, was effective in inhibiting the growth of M. ulcerans in the foot pads, and the effects were bactericidal. Effects of KRM-1648 at 0.0005% were bacteriostatic. Similar results were obtained with rifampicin, but only at concentrations of 0.008% and above. In established infection, i.e., when M. ulcerans were growing actively in footpads, bactericidal effects were observed with KRM-1648 at concentrations of 0.002% and above; to obtain similar results with rifampicin, the minimum dose was 0.032%. Thus, the results suggest the superiority of KRM-1648 over rifampicin in the treatment of M. ulcerans infection. The possibility of using KRM-1648 in combination with other antimycobacterial agents is discussed.
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PMID:In vivo susceptibility of Mycobacterium ulcerans to KRM-1648, a new benzoxazinorifamycin, in comparison with rifampicin. Anti-mycobacterial activity of KRM-1648. 1145 83

Mycobacterium avium growth in cultured human macrophages is influenced by serum lipids, transferrin and iron levels. Iron-saturated transferrin enhances M. avium growth, whereas apotransferrin inhibits mycobacterial replication. The ability of iron chelators to mimic the effects of transferrin on intracellular and extracellular M. avium growth was examined. Smooth, transparent, AIDS patient derived M. avium 7497 scrovar 4 was used to infect 7-day cultured human macrophages. Growth was measured by determining the colony-forming units (CFU) after infected macrophages were lysed 0 to 7 days after infection. The new iron chelating drug deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one or L1, CAS 30652-11-0), 1-ethyl-2-methyl-3-hydroxypyrid-4-one (L1NEt), 1-propyl-2-methyl-3-hydroxypyrid-4-one (L1NPr), 1-allyl-2-methyl-3-hyproxypyrid-4-one (L1NAll), and 3,4-dihydroxycinnamic acid enhanced intracellular and extracellular mycobacterial replication at concentrations of 0.1-2.5 micrograms/ml. 2-Pyridinecarboxaldehyde-2-quinolylhydrazone (PCQH) inhibited intracellular replication from 0.1-1.0 microgram/ml. Most, but not all of the PCQH-induced intracellular inhibition could be eliminated using iron at concentrations greater than 1.0 microgram/ml. Iron also suppressed the effects of PCQH on extracellular M. avium replication. These results indicate that iron chelators may have variable effects at different concentrations and can significantly alter both intracellular and extracellular M. avium replication. It is suggested that at low concentrations deferiprone and other aketohydroxypyridine chelators could enhance the growth of M. avium but at high concentrations may function as adjunct therapy with other antimicrobials against infections with M. avium. These findings are important for therapeutic considerations and dose protocol design in relation to the new iron chelating drug deferiprone, which is currently used in thalassaemia and other iron loaded patients, some of whom are suffering from AIDS.
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PMID:Effects on Mycobacterium avium replication in normal human macrophages by deferiprone (L1) and other iron chelators. Possible implications on toxicity. 1183 74

The palladium-catalyzed cross-coupling reaction of 5-(tributylstannyl)isoindoline and its 1- and 3-methyl derivatives with 6-fluoro or 6-unsubstituted 7-bromo-1-cyclopropyl-8-methoxy (or difluoromethoxy)-4-oxoquinoline-3-carboxylate afforded the corresponding 1-cyclopropyl-7-(5-isoindolinyl)-4-oxoquinoline-3- carboxylic acids: 6-fluoro, 1a-7a and 6-nonfluoro, 1b-7b. The in vitro antibacterial spectra of the newly synthesized quinolones were mostly characterized by excellent Gram-positive activity against Staphylococcus aureus and Streptococcus pneumoniae including quinolone-resistant strains, and also by significant Gram-negative activity comparable to 7-(1-piperazinyl)fluoroquinolones. Comparative examinations of the in vitro antibacterial profiles and the in vivo toxicity in terms of intravenous lethality, micronuclei-inducing potential and convulsive activity provided 6-nonfluorinated 1-cyclopropyl-8-(difluoromethoxy)-7-(1-methylisoindolin-5-yl)-4- oxoquinoline-3-carboxylic acid [(+/-)-5b] as the candidate for evaluation of the stereoisomers. The enantiomers (R)-5b and (S)-5b were synthesized via the Suzuki coupling reaction of (R)- and (S)-1-methyl derivatives of 2-(triphenylmethyl)isoindolin-5-boronic acid with the corresponding 7-bromo-8-(difluoromethoxy)-4- oxoquinoline-3-carboxylate. The (R)-5b stereoisomer proved to be 2- to 4-fold more active than the (S)-5b stereoisomer against the organisms tested, with the exception of an equal potency observed with S. pneumoniae IID553 and Haemophilus influenzae ATCC49247. A noticeable in vitro antibacterial profile of (R)-5b was that it is 16- and 64-fold more active than levofloxacin (CAS 100986-85-4) and ciprofloxacin (CAS 86393-32-0), respectively, against Mycoplasma pneumoniae IID813 (MIC of 0.0313 microgram/ml), and 4-fold more active than ciprofloxacin and levofloxacin against Mycobacterium tuberculosis M-4 (MIC of 0.0313 microgram/ml). Additional studies indicate that (R)-5b (T-3811, CAS 194804-75-6) exhibits excellent antibacterial activity against a wide range of organisms including anaerobes and common respiratory pathogens, while demonstrating a high selectivity against the mammalian homolog topoisomerases. The methane-sulfonate of (R)-5b (T-3811ME, CAS 223652-90-2) is now undergoing clinical testings.
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PMID:Synthesis, antibacterial activity, and toxicity of 7-(isoindolin-5-yl)-4-oxoquinoline-3-carboxylic acids. Discovery of the novel des-F(6)-quinolone antibacterial agent garenoxacin (T-3811 or BMS-284756). 1257 31

Despite well-developed tuberculosis (TB) control policies in Madagascar, the incidence of TB remains high and is estimated at about 100 new cases per 100000 inhabitants. This paper describes genetic characteristics of TB bacilli in Madagascar. Using an international spoligotyping database, SpolDB4, we also attempted to identify the origin of strains circulating in Madagascar. DNA polymorphism of 333 Mycobacterium tuberculosis complex isolates was assessed. A total of 301 isolates belonging to 60 spoligotyping-defined clusters were found, whereas 32 isolates harbored orphan patterns. By comparison with the international database, we identified a new genetic group of closely genetically related M. tuberculosis strains which we suggested to be specific from Madagascar. Most of them belonging to the East-African-Indian (EAI) superfamily of strains that are responsible for 14% of total TB cases (shared types ST1514-1525). These strains are closely related to the most prevalent shared type ST109, whose distribution is mainly confined to Madagascar. The observed distribution of genotypes shows that principal genetic group 1 strains (EAI, Beijing, CAS, Afri, "Manu") is high (35.4%) suggesting an ancient evolutionary history of tuberculosis in Madagascar, in relation to the origin of peopling and the demographic history.
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PMID:A study of spoligotyping-defined Mycobacterium tuberculosis clades in relation to the origin of peopling and the demographic history in Madagascar. 1616 40

Five carbohydrazides and 19 hydrazones of carboxylic acids of pyrrole were synthesized as new structural analogs of known tuberculostatics, such as isoniazid (CAS 54-85-3) and its popular hydrazones. The preliminary screening against Mycobacterium tuberculosis H37Rv (ATCC 27294) at 6.25 microg/mL in 12B medium using a broth microdilution assay, the Microplate Alamar Blue Assay (MABA) registered higher inhibitory activity within the hydrazones series (up to 68 % inhibition) compared with that of the carbohydrazides (0-34 %). No simple relationship between the activity of a particular hydrazone and that of the parent carbohydrazide, or correlations with the structural features introduced by the carbonyl partner could be observed. So both most active hydrazones diethyl 5-(2-[(2,4-dimethyl-1H-3-pyrrolyl)carbonyl]hydrazonomethyl)-3-methyl-1H-2,4-pyrroledicarboxylate (22, 68 % inhibition) and ethyl 5-(4-chlorophenyl)-2-methyl-1-(2-2-1-(5-nitro-2-furyl)methylidene]hydrazino-2-oxoethyl)-1H-3-pyrrolecarboxylate (32, 55 %) originated from inactive carbohydrazides (1, 0 % and 7, 10 % respectively); ethyl 1-(2-2-[1-(3-ethoxy-4-hydroxyphenyl) methylidene] hydrazino-2-oxoethyl)-2-methyl-5-(4-nitrophenyl)-1H-3-pyrrolecarboxylate (30) showed 0 % inhibition, although derived from a hydrazide with 34 % activity. The condensation of six carbohydrazides with the same carbonyl reagent 5-nitrofurfural yielded hydrazones whose activity covered the wide range of 0-55 % inhibition.
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PMID:Synthesis and preliminary screening of carbohydrazides and hydrazones of pyrrole derivatives as potential tuberculostatics. 1657 24

In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I-XII) and 3-[2-(4-carbethoxymethylthiazol-2-yl)imino-4-thiazoldinon-5-ylidenel-5-substituted/nonsubstituted IH-indole-2-one (XIII-XX) systems were synthesized. The structures were confirmed by spectral methods (UV, IR, 1H-NMR, 13C-NMR, 13C-DEPT (135), electron impact mass spectrometry) and elemental analysis. All compounds were tested for in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found to be active. Especially, compound I was more active than cefuroxime sodium (CAS 56238-63-2) which was used as a standard, and the activity of compound XII was close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228. Primary screening for antituberculous activity was conducted at 6.25 microg/ml against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. The anticonvulsant activities of selected prototoype compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200 mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice.
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PMID:Synthesis and evaluation of antimicrobial and anticonvulsant activities of some new 3-[2- (5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxymethylthiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and investigation of their structure-activity relationships. 1661 17

This survey identified the spoligopatterns of Mycobacterium tuberculosis strains with an international designation responsible for transmission and prevalence of TB (2000 to 2005) among native and immigrant populations of Tehran. The spacer oligonucleotides typing was performed on 1742 Mycobacterium tuberculosis strains isolated from verified cases of TB. Clinical and demographic data of patients were collected using traditional methods. A total of 133 distinct spoligopatterns was observed. 1679 clinical isolates were clustered in 70 clusters (52.5%) and 63 isolates were defined as orphans pattern (47.3%). Based on an international spoligotype database, the east African-Indian (EAI, 24%), central Asian (CAS, 20.8%), T clade (20.7%), Haarlem I (4.4%), Beijing (3.2%) and shared type 253 (3.1%) were the major identified M. tuberculosis superfamilies. Our results showed that the intra-community TB transmission was 13.7%, whereas the inter-community transmission was 39.3% for Afghanis and 20.3% for Iranians. The study highlighted the epidemic potential of specific genotypes (EAI, CAS, T clades) among tuberculosis cases in the Tehran territory. We also confirmed that the impact of transmission through immigration is low.
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PMID:The most prevalent Mycobacterium tuberculosis superfamilies among Iranian and Afghan TB cases. 1679 95


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