Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| enhancement of antibiotic activity by efflux inhibitors against multidrug resistant mycobacterium tuberculosis clinical isolates from brazil. | drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. the identification of m. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. in this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (tema) to study single combinations between antituberculosis drugs and efflux inhibitors (eis) against multidrug resistant m. tuberculosis cl ... | 2015 | 25972842 |
| comparison of sample preparation methods, instrumentation platforms, and contemporary commercial databases for identification of clinically relevant mycobacteria by matrix-assisted laser desorption ionization-time of flight mass spectrometry. | when mycobacteria are recovered in clinical specimens, timely species-level identification is required to establish the clinical significance of the isolate and facilitate optimization of antimicrobial therapy. matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) has recently been reported to be a reliable and expedited method for identification of mycobacteria, although various specimen preparation techniques and databases for analysis are reported across ... | 2015 | 25972426 |
| rapid whole-genome sequencing of mycobacterium tuberculosis isolates directly from clinical samples. | the rapid identification of antimicrobial resistance is essential for effective treatment of highly resistant mycobacterium tuberculosis. whole-genome sequencing provides comprehensive data on resistance mutations and strain typing for monitoring transmission, but unlike for conventional molecular tests, this has previously been achievable only from cultures of m. tuberculosis. here we describe a method utilizing biotinylated rna baits designed specifically for m. tuberculosis dna to capture ful ... | 2015 | 25972414 |
| biochemical characterization and computational identification of mycobacterium tuberculosis pyrazinamidase in some pyrazinamide-resistant isolates of iran. | pyrazinamide (pza) is one the first line anti-tuberculosis drugs that require activation by the pyrazinamidase (pzase). most pza-resistant mycobacterium tuberculosis strains have mutations in the pnca gene which encoding pzase that result in the reduction or loss of the enzyme activity. herein, we have examined how various mutations, which have been found from the pza-resistant m. tuberculosis strains in iran, modify the pzase activity. to elucidate the possible role of these mutations, namely a ... | 2015 | 25972249 |
| detection of low-level mixed-population drug resistance in mycobacterium tuberculosis using high fidelity amplicon sequencing. | undetected and untreated, low-levels of drug resistant (dr) subpopulations in clinical mycobacterium tuberculosis (mtb) infections may lead to development of dr-tuberculosis, potentially resulting in treatment failure. current phenotypic dr susceptibility testing has a theoretical potential for 1% sensitivity, is not quantitative, and requires several weeks to complete. the use of "single molecule-overlapping reads" (smor) analysis with next generation dna sequencing for determination of ultra-r ... | 2015 | 25970423 |
| [current issues arising from tuberculosis screening with interferon-gamma-release assays (igras)]. | a positive igra test does not always indicate a latent tuberculosis infection (ltbi); the prevalence of ltbi in the tested collective must be carefully considered in test interpretation. when igras are performed repeatedly in healthcare workers (big), variabilities of test results (conversions and reversions of the respective previous negative or positive result) can be expected. therefore only individuals for whom there is an established risk of being infected by mycobacterium tuberculosis (m.t ... | 2015 | 25970120 |
| chitosan-isoniazid conjugates: synthesis, evaluation of tuberculostatic activity, biodegradability and toxicity. | novel water-soluble chitosan-isoniazid conjugates were synthesized by two methods: (1) the carbodiimide method using isoniazid (inh) and n-(2-carboxyethyl)chitosan (cec), and (2) the reaction between inh and n-(3-chloro-2-hydroxypropyl)chitosan (chpc). the solubility of the conjugates under physiological conditions was enhanced by phosphorylation. method (1) is preferable in terms of obtaining conjugates with a high content of active substance; depending on reaction conditions, the degree of sub ... | 2015 | 25965488 |
| identification of novel inhibitors of mycobacterium tuberculosis pkng using pharmacophore based virtual screening, docking, molecular dynamics simulation, and their biological evaluation. | pkng is a ser/thr protein kinase that plays a crucial role in regulatory processes within the mycobacterial cell and signaling cascade of the infected host cell. the essentiality of pkng in mycobacterial virulence by blocking phagosome-lysosome fusion as well as its role in intrinsic antibiotic resistance makes it an attractive drug target. however, only very few compounds have been reported as mycobacterium tuberculosis pkng (mtpkng) inhibitors so far. therefore, in an effort to find potential ... | 2015 | 25965448 |
| rv2031c of mycobacterium tuberculosis: a master regulator of rv2028-rv2031 (hspx) operon. | genes belonging to the same operon are transcribed as a single mrna molecule in all prokaryotes. the genes of the same operon are presumed to be involved in similar metabolic and physiological processes. hence, computational analysis of constituent proteins could provide important clues to the functional relationships within the operonic genes. this tends to be more fruitful in the case of mycobacterium tuberculosis (mtb), considering the number of hypothetical genes with unknown functions and i ... | 2015 | 25964780 |
| the impact of maternal infection with mycobacterium tuberculosis on the infant response to bacille calmette-guérin immunization. | bacille calmette-guérin (bcg) immunization provides variable protection against tuberculosis. prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. we therefore hypothesized that maternal latent mycobacterium tuberculosis infection (ltbi) influences infant responses to bcg immunization at birth. we measured antibody (n = 53) and cellular (n = 31) responses to m. tuberculosis purified protein derivative (ppd) in infants of mothers with and without ltb ... | 2015 | 25964450 |
| moxifloxacin plus standard first-line therapy in the treatment of pulmonary tuberculosis: a meta-analysis. | the fluoroquinolone moxifloxacin has potent activity against mycobacterium tuberculosis and has been recommended by the guidelines for the treatment of pulmonary tuberculosis (tb). monotherapy is not recommended by the guidelines and only a few studies have evaluated the efficacy and safety of moxifloxacin plus standard first-line therapy in treating tb. the purpose of this meta-analysis was to further investigate the efficacy and safety of moxifloxacin plus standard therapy compared with standa ... | 2015 | 25964137 |
| identification of novel potential vaccine candidates against tuberculosis based on reverse vaccinology. | tuberculosis (tb) is a chronic infectious disease, considered as the second leading cause of death worldwide, caused by mycobacterium tuberculosis. the limited efficacy of the bacillus calmette-guérin (bcg) vaccine against pulmonary tb and the emergence of multidrug-resistant tb warrants the need for more efficacious vaccines. reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens by in silico approaches. m. tuberculosis h37rv proteome was analyzed with ne ... | 2015 | 25961021 |
| molecular basis of the activity and the regulation of the eukaryotic-like s/t protein kinase pkng from mycobacterium tuberculosis. | tuberculosis remains one of the world's deadliest human diseases, with a high prevalence of antibiotic-resistant mycobacterium tuberculosis (mtb) strains. a molecular understanding of processes underlying regulation and adaptation of bacterial physiology may provide novel avenues for the development of antibiotics with unconventional modes of action. here, we focus on the multidomain s/t protein kinase pkng, a soluble enzyme that controls central metabolism in actinobacteria and has been linked ... | 2015 | 25960409 |
| four decades of transmission of a multidrug-resistant mycobacterium tuberculosis outbreak strain. | the rise of drug-resistant strains is a major challenge to containing the tuberculosis (tb) pandemic. yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant tb in argentina. we estimate that the progenitor of the outbreak strain acquired re ... | 2015 | 25960343 |
| vitamin d supplementation: a comprehensive review on supplementation for tuberculosis prophylaxis. | vitamin d plays a large role in the innate immune response against mycobacterium tuberculosis (mtb) infection, activation and progression. likewise, vitamin d deficiency is shown by evidence presented here to be a known risk factor for developing both mtb infection and active tuberculosis (tb). this comprehensive review discusses the evidence and remaining questions regarding vitamin d supplementation as a prophylactic measure in those who are at high risk of mtb infection and active tb. vitamin ... | 2015 | 25959993 |
| [immunogenicity evaluation of mycobacterium tuberculosis mpt83 protein and establishment of serological diagnostic method for bovine tuberculosis detection]. | the aim of this study was to express mycobacterium tuberculosis mpt83 protein and to evaluate its immunogenicity in murine model as well as the serological diagnosis potential value for bovine tuberculosis. | 2015 | 25958703 |
| batf2/irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection. | basic leucine zipper transcription factor batf2 is poorly described, whereas batf and batf3 have been shown to play essential roles in dendritic cell, t cell, and b cell development and regulation. batf2 was drastically induced in ifn-γ-activated classical macrophages (m1) compared with unstimulated or il-4-activated alternative macrophages (m2). batf2 knockdown experiments from ifn-γ-activated macrophages and subsequent expression profiling demonstrated important roles for regulation of immune ... | 2015 | 25957166 |
| cd4+ t cell polyfunctional profile in hiv-tb coinfection are similar between individuals with latent and active tb infection. | cd4+ t cell counts of hiv-infected individuals with pulmonary tb (ptb) are higher than with other opportunistic infections suggesting that progression to ptb is not merely due to t cell depletion but also dysfunction. there are limited data examining t cell functional signatures in human hiv-tb co-infection particularly in ptb which accounts for about 80% of active tb disease overall. we examined a cohort of hiv-infected anti-retroviral naïve individuals in kampala, uganda, a tb endemic area usi ... | 2015 | 25956974 |
| lipid metabolism and type vii secretion systems dominate the genome scale virulence profile of mycobacterium tuberculosis in human dendritic cells. | mycobacterium tuberculosis continues to kill more people than any other bacterium. although its archetypal host cell is the macrophage, it also enters, and survives within, dendritic cells (dcs). by modulating the behaviour of the dc, m. tuberculosis is able to manipulate the host's immune response and establish an infection. to identify the m. tuberculosis genes required for survival within dcs we infected primary human dcs with an m. tuberculosis transposon library and identified mutations wit ... | 2015 | 25956932 |
| transcription factor regulatory network for early lung immune response to tuberculosis in mice. | numerous transcription factors (tfs) have been suggested to have a role in mycobacterium tuberculosis infection; however, the tfs involved in the early immune response of lung cells remains to be fully elucidated. the present study aimed to identify tfs which may have a role in the early immune response to tuberculosis and the gene regulatory networks in which they are involved. gene expression data obtained from microarray analysis of the early lung immune response to tuberculosis (gene express ... | 2015 | 25955085 |
| profiling b and t cell immune responses to co-infection of mycobacterium tuberculosis and hookworm in humans. | humoral and cellular immune responses play protective roles against mycobacterium tuberculosis (mtb) infection. however, hookworm infection decreases the immune response to hookworm and bystander antigens. currently, immune responses to co-infection of mtb and hookworm are still unknown, although co-infection has been one of the public health problems in co-endemic areas of pulmonary tuberculosis (ptb) and hookworm disease. therefore, it is essential to evaluate b and t cell immune responses to ... | 2015 | 25954506 |
| the indirect microscopic observation drug susceptibility assay demonstrated high concordance with the indirect mgit method for pyrazinamide susceptibility testing. | the microscopic observation drug susceptibility (mods) assay has been used for mycobacterium tuberculosis detection and anti-tb drug susceptibility tests for several years, and our study aimed to evaluate the accuracy of mods in detecting pyrazinamide resistance in mdr tb suspects. | 2015 | 25953803 |
| draft genome sequence of mycobacterium tuberculosis strain e186hv of beijing b0/w lineage with reduced virulence. | we report a draft genome sequence of mycobacterium tuberculosis strain e186hv, belonging to the beijing b0/w lineage and isolated from a patient from kurgan, russia. this clinical isolate showed a reduced virulence phenotype unusual for this lineage and resistance to isoniazid, rifampin, ethambutol, pyrazinamide, and ofloxacin. we analyzed single nucleotide polymorphisms (snps) associated with virulence. | 2015 | 25953188 |
| challenges in assessing transmission of mycobacterium tuberculosis in long-term-care facilities. | 2015 | 25952618 | |
| sila-421 activity in vitro against rifampicin-susceptible and rifampicin-resistant mycobacterium tuberculosis, and in vivo in a murine tuberculosis model. | due to the emergence of multidrug-resistant and extensively drug-resistant tuberculosis (tb), there is an urgent need for new tb drugs or for compounds that improve the efficacy of currently used drugs. in this study, time-kill kinetics of sila-421 as a single drug and in combination with isoniazid (inh), rifampicin (rif), moxifloxacin (mxf) or amikacin (amk) against mycobacterium tuberculosis were assessed. therapeutic efficacy in vivo in a mouse tb model was also studied. further in vitro anal ... | 2015 | 25951996 |
| correlations between drug resistance of beijing/w lineage clinical isolates of mycobacterium tuberculosis and sublineages: a 2009-2013 prospective study in xinjiang province, china. | the prevalence of drug-resistant tuberculosis (tb) in xinjiang is higher than in other regions of china, and beijing/w lineage mycobacterium tuberculosis (mtb) is the dominant strain of mtb in xinjiang. however, information on multidrug-resistant (mdr) and extensively drug-resistant (xdr) tb, particularly the correlation between mdr and the beijing/w lineage and the correlation between drug resistance and the beijing/w sublineage strains, is limited. | 2015 | 25950148 |
| the application of genexpert mtb/rif for smear-negative tb diagnosis as a fee-paying service at a south asian general hospital. | the genexpert mtb/rif assay (xpert) is a novel automated diagnostic tool for tuberculosis but its optimal placement in the healthcare system has not been determined. the objective of this study was to determine the possibility of additional case detection for pulmonary tuberculosis (ptb) by offering xpert to smear-negative patients in a low-hiv burden setting with no mycobacterium tuberculosis (m.tb.) culture facilities. patients routinely presenting with symptoms suggestive of ptb with negative ... | 2015 | 25949825 |
| a first step toward liposome-mediated intracellular bacteriophage therapy. | the emergence of antibiotic-resistant bacteria presents a severe challenge to medicine and public health. while bacteriophage therapy is a promising alternative to traditional antibiotics, the general inability of bacteriophages to penetrate eukaryotic cells limits their use against resistant bacteria, causing intracellular diseases like tuberculosis. bacterial vectors show some promise in carrying therapeutic bacteriophages into cells, but also bring a number of risks like an overload of bacter ... | 2015 | 25937143 |
| prevalence and risk factors of mixed mycobacterium tuberculosis complex infections in china. | mixed infections have been considered as a potential obstacle for tuberculosis treatment and control. to date, few studies have been done to determine the rate of mixed infections of mycobacterium tuberculosis in china. | 2015 | 25936744 |
| diagnostic accuracy study of multiplex pcr for detecting tuberculosis drug resistance. | to study the diagnostic accuracy of a multiplex real-time pcr (anyplex ii mtb/mdr/xdr, seegene, corea) that detects mycobacterium tuberculosis resistant to isoniazid (inh), rifampicin (rif), fluoroquinolones (flq) and injectable drugs (kanamycin [kan], amikacin [amk] and capreomycin [cap]) in isolates and specimens. | 2015 | 25936742 |
| ifn-γ/tnf-α ratio in response to immuno proteomically identified human t-cell antigens of mycobacterium tuberculosis - the most suitable surrogate biomarker for latent tb infection. | the enormous reservoir of latent tb infection (ltbi) poses a major hurdle for global tb control. the existing tuberculin skin test (tst) and ifn-γ release assays (igras) are found to be suboptimal for ltbi diagnosis. previously we had taken an immunoproteomic approach and identified 10 protein fractions (contains 16 proteins), which are solely recognized by ltbi. in a cohort of 40 pulmonary tb patients (ptb) and 35 healthy household contacts (hhc), ifn-γ and tnf-α response were measured against ... | 2015 | 25936741 |
| a double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine aeras-402, an adenovirus-vectored fusion protein, in healthy, bcg-vaccinated infants. | several novel tuberculosis vaccines are currently in clinical trials, including aeras-402, an adenovector encoding a fusion protein of mycobacterium tuberculosis antigens 85a, 85b, and tb10.4. a multicentred trial of aeras-402 safety and immunogenicity in healthy infants was conducted in three countries in sub-saharan africa, using an adaptive design. | 2015 | 25936724 |
| altered cytokine profiles in children with indeterminate quantiferon results and common infections. | an increased rate of indeterminate quantiferon results (low ifn-γ release in the phytohemagglutinin-stimulated tube) has been reported in children with clinical signs compatible with tuberculosis but with the final diagnosis of infectious diseases different from tuberculosis. here, we addressed the mechanisms involved and assessed potential alternative biomarkers to overcome indeterminate quantiferon results under these conditions. | 2015 | 25936633 |
| new anti-tuberculosis drugs and regimens: 2015 update. | over 480 000 cases of multidrug-resistant (mdr) tuberculosis (tb) occur every year globally, 9% of them being affected by extensively drug-resistant (xdr) strains of mycobacterium tuberculosis. the treatment of mdr/xdr-tb is unfortunately long, toxic and expensive, and the success rate largely unsatisfactory (<20% among cases with resistance patterns beyond xdr). the aim of this review is to summarise the available evidence-based updated international recommendations to manage mdr/xdr-tb, and to ... | 2015 | 27730131 |
| cytokinins beyond plants: synthesis by mycobacterium tuberculosis. | mycobacterium tuberculosis (m. tuberculosis) resides mainly inside macrophages, which produce nitric oxide (no) to combat microbial infections. earlier studies revealed that proteasome-associated genes are required for m. tuberculosis to resist no via a previously uncharacterized mechanism. twelve years later, we elucidated the link between proteasome function and no resistance in m. tuberculosis in molecular cell, 57 (2015), pp. 984-994. in a proteasome degradation-defective mutant, rv1205, a h ... | 2015 | 28357289 |
| genetic diversity and drug susceptibility profile of mycobacterium tuberculosis isolated from different regions of india. | molecular genotyping profiles of mycobacterium tuberculosis (mtb) provide a valuable insight into the evolution and transmission of the bacilli. due to the lack of comprehensive national level data from india on this subject, we performed this study to determine the recent trends and distribution of various mtb lineages circulating in india. | 2015 | 25934327 |
| effect of active case finding on prevalence and transmission of pulmonary tuberculosis in dhaka central jail, bangladesh. | understanding tuberculosis (tb) transmission dynamics is essential for establishing effective tb control strategies in settings where the burden and risk of transmission are high. the objectives of this study were to evaluate the effect of active screening on controlling tb transmission and also to characterize mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. | 2015 | 25933377 |
| doubly end-on azido bridged mixed-valence cobalt trinuclear complex: spectral study, vtm, inhibitory effect and antimycobacterial activity on human carcinoma and tuberculosis cells. | doubly end-on azido-bridged mixed-valence trinuclear cobalt complex, [co3(l)2(n3)6(ch3oh)2] (1) is afforded by employing a potential monoanionic tetradentate-n2o2 schiff base precursor (2-[{[2-(dimethylamino)ethyl]imino}methyl]-6-methoxyphenol; hl). single crystal x-ray structure reveals that in 1, the adjacent co(ii) and co(iii) ions are linked by double end-on azido bridges and thus the full molecule is generated by the site symmetry of a crystallographic twofold rotation axis. complex 1 is su ... | 2015 | 25932976 |
| comparison of advansure tb/ntm pcr and cobas taqman mtb pcr for detection of mycobacterium tuberculosis complex in routine clinical practice. | the advansure tuberculosis/non-tuberculous mycobacterium (tb/ntm) pcr (lg life science, korea) and cobas taqman mycobacterium tuberculosis (mtb) pcr (roche diagnostics, usa) are commonly used in clinical microbiology laboratories. we aimed to evaluate these two commercial real-time pcr assays for detection of mtb in a large set of clinical samples over a two-year period. advansure tb/ntm pcr and cobas taqman mtb pcr were performed on 9,119 (75.2%) and 3,010 (24.8%) of 12,129 (9,728 respiratory a ... | 2015 | 25932446 |
| complete genome sequence of the clinical beijing-like strain mycobacterium tuberculosis 323 using the pacbio real-time sequencing platform. | we report here the whole-genome sequence of the multidrug-resistant beijing-like strain mycobacterium tuberculosis 323, isolated from a 15-year-old female patient who died shortly after the initiation of second-line drug treatment. this strain is representative of the beijing-like isolates from colombia, where this lineage is becoming a public health concern. | 2015 | 25931600 |
| pseudoclavibacter otitis media in a 3-year-old boy with pulmonary and spinal tuberculosis. | pseudoclavibacter has rarely been documented as an etiologic agent of infection in humans. we presented the first case report of pseudoclavibacter otitis media in a boy with pulmonary and spinal tuberculosis.a 3-year-old boy was referred to our hospital due to prolonged fever and progressive paraplegia for 3 months. he had yellowish discharge from both ear canals. the pleural fluid culture was positive for mycobacterium tuberculosis. the discharge from both ears culture yielded yellow colonies o ... | 2015 | 25929901 |
| association of cybb polymorphisms with tuberculosis susceptibility in the chinese han population. | reactive oxygen species (ros) play a major role in the nonspecific innate immune response to invading microorganisms, such as mycobacterium tuberculosis (mtb). gp91phox, encoded by cybb, serves as a key functional subunit of the nicotinamide adenine dinucleotide phosphate (nadph) oxidase complex, which is pivotal to ros generation. therefore, the aim of the study was to investigate the association of cybb polymorphisms with tuberculosis (tb) susceptibility. | 2015 | 25929165 |
| duality of lipid mediators in host response against mycobacterium tuberculosis: good cop, bad cop. | lipid mediators play an important role in infection- and tissue injury-driven inflammatory responses and in the subsequent inhibition and resolution of the response. here, we discuss recent findings that substantiate how mycobacterium tuberculosis promotes its survival in the host by dysregulation of lipid mediator balance. by inhibiting prostaglandin e2 (pge2) and enhancing lipoxin production, m. tuberculosis induces necrotic death of the macrophage, an environment that favors its growth. these ... | 2015 | 25926980 |
| a novel reporter phage to detect tuberculosis and rifampin resistance in a high-hiv-burden population. | improved diagnostics and drug susceptibility testing for mycobacterium tuberculosis are urgently needed. we developed a more powerful mycobacteriophage (φ(2)gfp10) with a fluorescent reporter. fluorescence-activated cell sorting (facs) allows for rapid enumeration of metabolically active bacilli after phage infection. we compared the reporter phage assay to genexpert mtb/rif for detection of m. tuberculosis and rifampin (rif) resistance in sputum. patients suspected to have tuberculosis were pro ... | 2015 | 25926493 |
| diagnostic yield of sputum microbiological analysis in the diagnosis of pulmonary tuberculosis in a period of 10 years. | pulmonary tuberculosis (tb) requires an early diagnosis for prompt introduction of treatment and prevention of transmission. definitive diagnosis is obtained by microbiological culture and identification of mycobacterium tuberculosis in respiratory specimens, mostly sputum samples. | 2015 | 25926254 |
| a multi-scale approach to designing therapeutics for tuberculosis. | approximately one third of the world's population is infected with mycobacterium tuberculosis. limited information about how the immune system fights m. tuberculosis and what constitutes protection from the bacteria impact our ability to develop effective therapies for tuberculosis. we present an in vivo systems biology approach that integrates data from multiple model systems and over multiple length and time scales into a comprehensive multi-scale and multi-compartment view of the in vivo immu ... | 2015 | 25924949 |
| structural views of quinone oxidoreductase from mycobacterium tuberculosis reveal large conformational changes induced by the co-factor. | energy generation, synthesis of biomass and detoxification of synthetic compounds are driven by electron transfer in all living organisms. soluble quinone oxidoreductases (qors) catalyze transfer of electrons from nadph to substrates. the open reading frame rv1454c of mycobacterium tuberculosis (mtb) encodes a nadph-dependent qor that is known to catalyze one-electron reduction of quinones to produce semiquinones. here, we report the crystal structures of the apo-enzyme of mtbqor and its binary ... | 2015 | 25924579 |
| virtually designed triclosan-based inhibitors of enoyl-acyl carrier protein reductase of mycobacterium tuberculosis and of plasmodium falciparum. | we report here new chemical structures of predicted nanomolar triclosan-based inhibitors (tcls) of mycobacterium tuberculosis enoyl-acyl carrier protein reductase (inha) virtually proposed by computer-assisted molecular design. 3d models of inha-tcl complexes were prepared by in situ modifications of the reference crystal structure (pdb entry 1p45) for a training set of 15 tcls with known inha inhibitory activities. a qsar model was built leading to linear correlation between the calculated free ... | 2015 | 27490275 |
| synthesis, anti-mycobacterial activity and dna sequence-selectivity of a library of biaryl-motifs containing polyamides. | the alarming rise of extensively drug-resistant tuberculosis (xdr-tb) strains, compel the development of new molecules with novel modes of action to control this world health emergency. distamycin analogues containing n-terminal biaryl-motifs 2(1-5)(1-7) were synthesised using a solution-phase approach and evaluated for their anti-mycobacterial activity and dna-sequence selectivity. thiophene dimer motif-containing polyamide 2(2,6) exhibited 10-fold higher inhibitory activity against mycobacteri ... | 2015 | 25921267 |
| evaluation of rapid methods for diagnosis of tuberculosis in slaughtered free-range pigs. | free-range pigs can be infected by mycobacterium tuberculosis complex (mtc) and may contribute to the spread of bovine tuberculosis (btb). in the present study, the diagnostic values of bacteriological culture, a duplex real-time quantitative pcr and an antibody elisa were evaluated in an abattoir study of submandibular lymph nodes and serum samples from 73 pigs with and without lesions consistent with btb. the duplex qpcr was an accurate method for diagnosis of tb in pigs (specificity 100%; sen ... | 2015 | 25920761 |
| synthesis and anti-mycobacterial activity of 2-chloronicotinaldehydes based novel 1h-1,2,3-triazolylbenzohydrazides. | 1h-1,2,3-triazolylbenzohydrazides (6a-h and 11a-l) were synthesized from 2-chloronicotinaldehydes and evaluated for anti-mycobacterial activity against mycobacterium tuberculosis h37rv strain (atcc-27294). seven compounds 6b, 6e,f, 11d, 11h, 11j and 11l displayed potent anti-mycobacterial activity (mic 2.8-6.2 μm). potent anti-mycobacterial compounds were chosen for cytotoxicity studies by mtt protein assay against normal cell lines (pbmc and raw 264.7) and shown low cytotoxicity. this is the fi ... | 2015 | 25908515 |
| [application of melting curve assay in the quality assessment of drug susceptibility test on mycobacterium tuberculosis]. | to evaluate the feasibility of melting curve assay technologies in quality assessment of drug susceptibility test (dst) on mycobacterium tuberculosis. | 2015 | 25908419 |
| mycobacterium tuberculosis rpfe promotes simultaneous th1- and th17-type t-cell immunity via tlr4-dependent maturation of dendritic cells. | reciprocal induction of the th1 and th17 immune responses is essential for optimal protection against mycobacterium tuberculosis (mtb); however, only a few mtb antigens are known to fulfill this task. a functional role for resuscitation-promoting factor (rpf) e, a latency-associated member of the rpf family, in promoting naïve cd4(+) t-cell differentiation toward both th1 and th17 cell fates through interaction with dendritic cells (dcs) was identified in this study. rpfe induces dc maturation b ... | 2015 | 25907170 |
| mycobacterium diagnostics: from the primitive to the promising. | the field of clinical microbiology has been revolutionised by genomic and proteomic methods, which have facilitated more rapid diagnosis and characterisation of infection in many cases. in contrast, mycobacteriological evolution has tended to retain the traditional methods of smear microscopy for detection of acid-fast bacilli to indicate mycobacteria, along with culture, and in synergy with more modern molecular methods. thus, efforts have been focused on reducing the time to diagnosis of infec ... | 2015 | 25906489 |
| immunogenicity and protective efficacy of dmt liposome-adjuvanted tuberculosis subunit ctt3h vaccine. | different strategies have been proposed for the development of protein subunit vaccine candidates for tuberculosis (tb), which shows better safety than other types of candidates and the currently used bacillus calmette-guérin (bcg) vaccine. in order to develop more effective protein subunits depending on the mechanism of cell-mediated immunity against tb, a polyprotein ctt3h, based on 5 immunodominant antigens (cfp10, tb10.4, tb8.4, rv3615c, and hbha) with cd8(+) epitopes of mycobacterium tuberc ... | 2015 | 25905680 |
| diterpenes synthesized from the natural serrulatane leubethanol and their in vitro activities against mycobacterium tuberculosis. | seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the maba technique for their activity against the h37rv strain of mycobacterium tuberculosis. some compounds showed antimycobacterial selectivity indices higher than leubethanol. | 2015 | 25905603 |
| predictive power of etre polymorphism and katg463 mutation to inh-resistance of m.tuberculosis. | the miru-vntr polymorphism and katg463 mutation are used to genotype the mycobacterium tuberculosis, but the correlation between them and inh-resistance were unknown. this study was aimed to explore whether etre polymorphism and katg463 mutation could predict the inh-resistance, and the relationship between etre polymorphism and katg463 mutation. | 2015 | 25905061 |
| a humanized monoclonal antibody against heat shock protein 60 suppresses murine arthritis and colitis and skews the cytokine balance toward an anti-inflammatory response. | we have previously shown that naturally occurring as well as acquired abs against the mycobacterium tuberculosis heat shock protein (hsp)65 protect against the induction of murine autoimmune inflammatory arthritis. in the present work, we have studied the anti-inflammatory effect of prozumab, a humanized anti-hsp mab in murine inflammatory arthritis and colitis, and its effects on cytokine secretion. prozumab was shown to bind to hsp60, the highly conserved mammalian homolog of the bacterial pro ... | 2015 | 25904550 |
| mixed infections and rifampin heteroresistance among mycobacterium tuberculosis clinical isolates. | mixed infections and heteroresistance of mycobacterium tuberculosis contribute to the difficulty of diagnosis, treatment, and control of tuberculosis. however, there is still no proper solution for these issues. this study aimed to investigate the potential relationship between mixed infections and heteroresistance and to determine the high-risk groups related to these factors. a total of 499 resistant and susceptible isolates were subjected to spoligotyping and 24-locus variable-number tandem r ... | 2015 | 25903578 |
| whole genome sequence analysis of multidrug-resistant mycobacterium tuberculosis beijing isolates from an outbreak in thailand. | the mycobacterium tuberculosis beijing family is often associated with multidrug resistance and large outbreaks. conventional genotyping study of a community outbreak of multidrug-resistant tuberculosis (mdr-tb) that occurred in kanchanaburi province, thailand was carried out. the study revealed that the outbreak was clonal and the strain was identified as a member of beijing family. although, the outbreak isolates showed identical spoligotyping and mycobacterial interspersed repetitive units-va ... | 2015 | 25903079 |
| when a respiratory pathogen turns to the skin: cutaneous tuberculosis in a lung transplant patient. | a 62-year-old male, who received immune suppressive therapy due to a lung transplantation several years ago, developed multiple painful abscesses in the right forearm. first misdiagnosed as staphylococcal abscesses, mycobacterium tuberculosis was eventually cultured from the abscesses. in addition, the patient also suffered from pulmonary tuberculosis and respiratory specimens were also culture-positive for mycobacterium tuberculosis. cutaneous tuberculosis must be kept as a differential diagnos ... | 2015 | 25902867 |
| prevalence of smear positive pulmonary tuberculosis in gondar prisoners, north west ethiopia. | to assess the prevalence and risk factors of smear positive pulmonary tuberculosis among gondar town prisoners, north west ethiopia. | 2015 | 25902026 |
| characterization of mycobacterium isolates from pulmomary tuberculosis suspected cases visiting tuberculosis reference laboratory at ethiopian health and nutrition research institute, addis ababa ethiopia: a cross sectional study. | to characterize mycobacterium isolates from pulmomary tuberculosis suspected cases visiting national tuberculosis reference laboratory at ethiopian health and nutrition research institute, for diagnosis of pulmonary tuberculosis from january 4 to february 22, 2010 with total samples of 263. | 2015 | 25901922 |
| prevalence of tuberculosis in faridabad district, haryana state, india. | epidemiological information on tuberculosis (tb) has always been vital for planning control strategies. it has now gained further importance for monitoring the impact of interventions to control the disease. the present study was done to estimate the prevalence of bacillary tuberculosis in the district of faridabad in haryana state of india among persons aged older than 15 years. | 2015 | 25900959 |
| isoniazid induced acute pancreatitis in a young girl. | isoniazid (inh) is the mainstay of management against mycobacterium tuberculosis. inh-induced acute pancreatitis is an uncommon association and with dearth of literature on it. we are reporting a case of an 11 years old girl who developed acute pancreatitis after 2 weeks of antituberculous therapy. an inh free regimen was started. she was discharged and followed without complications. | 2015 | 25899200 |
| sensitivity pattern of second line anti-tuberculosis drugs against clinical isolates of multidrug resistant mycobacterium tuberculosis. | to determine the current sensitivity pattern of second line anti-tuberculosis drugs against clinical isolates of multidrug resistant mycobacterium tuberculosis (mdr-tb). | 2015 | 25899188 |
| the psp system of mycobacterium tuberculosis integrates envelope stress-sensing and envelope-preserving functions. | the bacterial envelope integrates essential stress-sensing and adaptive functions; thus, envelope-preserving functions are important for survival. in gram-negative bacteria, envelope integrity during stress is maintained by the multi-gene psp response. mycobacterium tuberculosis was thought to lack the psp system since it encodes only pspa and no other psp ortholog. intriguingly, pspa maps downstream from clgr, which encodes a transcription factor regulated by the mprab-σ(e) envelope-stress-sign ... | 2015 | 25899163 |
| [antituberculous in vitro activity of helichrýsum arenárium extract]. | bacteriostatic and bactericidal activity of aqueous solution (50 mg/ml) of alcoholic extract of helichrýsum arenárium (l.) dried flowers, prepared by a special technique so as to increase the yield of flavonoids, was studied in vitro with respect to mycobacterium tuberculosis (mbt) strains possessing varying degrees of drug resistance, as characterized by replacements ser r leu (modification of b-subunit rna-polymerase of mbt) and ser r thr (inactivation of mbt catalase-peroxidase enzyme). the m ... | 2015 | 25898545 |
| pro- and anti-inflammatory cytokines against rv2031 are elevated during latent tuberculosis: a study in cohorts of tuberculosis patients, household contacts and community controls in an endemic setting. | tuberculosis (tb) is among the leading causes of morbidity and mortality. the causative agent, mycobacterium tuberculosis (mtb), has evolved virulent factors for entry, survival, multiplication and immune evasion. rv2031 (also called alpha crystallin, hspx, 16-kda antigen), one of the most immunogenic latency antigens, is believed to play a key role in long-term viability of mtb. here, we report the dynamics of pro-inflammatory (ifn-γ, tnf-α) and anti-inflammatory (il-10) cytokines against rv203 ... | 2015 | 25897840 |
| covalent modification of the mycobacterium tuberculosis fas-ii dehydratase by isoxyl and thiacetazone. | isoxyl and thiacetazone are two antitubercular prodrugs formerly used in the clinical treatment of tuberculosis. although both prodrugs have recently been shown to kill mycobacterium tuberculosis through the inhibition of the dehydration step of the type ii fatty acid synthase pathway, their detailed mechanism of inhibition, the precise number of enzymes involved in their activation and the nature of their activated forms remained unknown. we here demonstrate that both isoxyl and thiacetazone sp ... | 2015 | 25897434 |
| autophagy regulation revealed by sapm-induced block of autophagosome-lysosome fusion via binding rab7. | the mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. our previous study shows lpqh, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. it is well known that sapm, another virulence factor, plays an important role in blocking phagosome-endosome fusion. however, the mechanism that sapm interferes with autophagy remains poorly defined. in this study, we report that sapm suppresses the autophagy flux by bl ... | 2015 | 25896765 |
| bioluminescence for assessing drug potency against nonreplicating mycobacterium tuberculosis. | targeting dormant mycobacterium tuberculosis represents a challenge to antituberculosis drug discovery programs. we previously reported and validated the use of the streptomycin (str)-dependent m. tuberculosis 18b strain as a tool for assessing drug potency against nonreplicating bacteria both in vitro and in vivo. in this study, we generated a luminescent 18b strain, named 18b-lux, by transforming the bacteria with a vector expressing the luxcdabe operon from photorhabdus luminescens. luciferas ... | 2015 | 25896710 |
| dysregulation of apoptosis is a risk factor for tuberculosis disease progression. | a major barrier to effective tuberculosis control is our limited understanding of risk factors for tuberculosis disease progression. this study examined the role of apoptosis in immunity to tuberculosis. | 2015 | 25895988 |
| [expression of mycobacterium tuberculosis small rnas in mice models of tuberculosis]. | identification of mechanisms that contribute to bacterial pathogens survival in the infected organism is a powerful approach to influence the pathogenic bacteria. recently it was established that bacteria use small rnas to regulate their metabolism. we studied the expression level of the three most highly expressed m. tuberculosis small rnas mts0997, mts 1338 and mts2823 at different stages of infection in. mice with different genetic resistance to tuberculosis. the maximum expression level of t ... | 2015 | 25895346 |
| correction: crystal structures of the kinase domain of the sulfate-activating complex in mycobacterium tuberculosis. | 2015 | 25894551 | |
| treatment-resistant recurrent membranoproliferative glomerulonephritis in renal allograft responding to rituximab: case report. | we report a case of idiopathic membranoproliferative glomerulonephritis (mpgn) recurring 2 years after a living-unrelated kidney transplantation. the disease was refractory to intravenous immunoglobulin and plasmapheresis. treatment with 2 doses of rituximab resulted in remission of the disease. the disease relapsed 18 months later after an episode of cytomegalovirus pneumonitis. after treatment of the pneumonitis, a lung biopsy was performed owing to persistent chest symptoms, which revealed br ... | 2015 | 25891740 |
| is the beijing strain of mycobacterium tuberculosis associated with cavitary lung disease? | we conducted a cross-sectional study to describe clinical characteristics of patients with pulmonary tuberculosis with and without evidence of pulmonary cavitation on chest radiography and assess whether cavitation is associated with infection with mycobacterium tuberculosis beijing strain. cases were selected from the tuberculosis registry (january 1, 2008-november 1, 2011) of the florida department of health (fdoh). molecular characterization was performed by spoligotyping and miru-vntr. we an ... | 2015 | 25891279 |
| crystal structure of the enoyl-acp reductase of mycobacterium tuberculosis (inha) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach. | inha is an enoyl-acp reductase of mycobacterium tuberculosis implicated in the biosynthesis of mycolic acids, essential constituents of the mycobacterial cell wall. to date, this enzyme is considered as a promising target for the discovery of novel antitubercular drugs. in this work, we describe the first crystal structure of the apo form of the wild-type inha at 1.80å resolution as well as the crystal structure of inha in complex with the synthetic metabolite of the antitubercular drug isoniazi ... | 2015 | 25891098 |
| diagnosis of tuberculous meningitis: challenges and promises. | tuberculosis (tb) which is caused by mycobacterium tuberculosis infects primarily the lungs but it also affects other parts of the body. tuberculous meningitis (tbm) is the most severe form of tb and has the highest mortality and morbidity rate compared to other forms of tb. it is common in young children and hiv-infected patients, but is also seen in adults. despite anti-tuberculosis treatment, tbm is still a major cause of death and neurological sequelae as treatment given to the patients is o ... | 2015 | 25890607 |
| ag 85, a major secretion protein of mycobacterium tuberculosis, can be identified in ancient bone. | for the confirmation of ag 85 in ancient and recent ecm of native macerated human bone, five cases were investigated. in three individuals, highly positive results for ag 85 were identified in western blot: 1) a male from arzhan, south siberia, dating from the 7th century bc, 2) a male from kirchberg in hesse, germany, dating from the 10th - 12th century ad and 3) a recent female with a proven diagnosis of tb. as a negative control, a recent male is presented who did not suffer from tb. in anoth ... | 2015 | 25890594 |
| a rare complication of pulmonary tuberculosis: a case report. | pulmonary tuberculosis remains an important public health problem globally and one of the most prevalent infectious diseases in sri lanka. it can cause a wide variety of complications but hematological manifestations are rare. according to our literature survey, this is the first reported case of the disease associated with deep vein thrombosis in sri lanka. | 2015 | 25888831 |
| caspase-3-independent apoptotic pathways contribute to interleukin-32γ-mediated control of mycobacterium tuberculosis infection in thp-1 cells. | macrophages are the primary effector cells responsible for killing mycobacterium tuberculosis (mtb) through various mechanisms, including apoptosis. however, mtb can evade host immunity to create a favorable environment for intracellular replication. mtb-infected human macrophages produce interleukin-32 (il-32). il-32 is a pro-inflammatory cytokine and has several isoforms. we previously found that il-32γ reduced the burden of mtb in human macrophages, in part, through the induction of caspase-3 ... | 2015 | 25887904 |
| wnt/β-catenin signaling reduces bacillus calmette-guerin-induced macrophage necrosis through a ros -mediated parp/aif-dependent pathway. | necrosis of alveolar macrophages following mycobacterium tuberculosis infection has been demonstrated to play a vital role in the pathogenesis of tuberculosis. our previous study demonstrated that wnt/β-catenin signaling was able to promote mycobacteria-infected cell apoptosis by a caspase-dependent pathway. however, the functionality of this signaling in the necrosis of macrophage following mycobacterial infection remains largely unknown. | 2015 | 25887795 |
| expression of inhibitory regulators of innate immunity in patients with active tuberculosis. | tuberculosis (tb) is an important cause of morbidity and mortality worldwide. toll-like-receptors (tlrs) are important for the recognition of the causative agent mycobacterium tuberculosis. negative regulation of tlrs is necessary to control deleterious inflammatory damage, but could provide a means of immune evasion by m. tuberculosis as well. | 2015 | 25887604 |
| prediction of host - pathogen protein interactions between mycobacterium tuberculosis and homo sapiens using sequence motifs. | emergence of multiple drug resistant strains of m. tuberculosis (mdr-tb) threatens to derail global efforts aimed at reigning in the pathogen. co-infections of m. tuberculosis with hiv are difficult to treat. to counter these new challenges, it is essential to study the interactions between m. tuberculosis and the host to learn how these bacteria cause disease. | 2015 | 25887594 |
| tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant mycobacterium tuberculosis clinical isolates. | tetrandrine is a natural chemical product purified from fourstamen stephania root which recently has been shown to act similarly as synthesized drug efflux pump inhibitor verapamil. the aim of the study is to examine whether tetrandrine could potentiate anti-tubercular drugs to which mycobacterium tuberculosis (mtb) has turned resistant via efflux mechanisms. | 2015 | 25887373 |
| laryngeal tuberculosis diagnosed by stool sample cultures: a case report. | laryngeal tuberculosis is a rare and often misdiagnosed disease. its diagnosis is based on the association of a laryngeal lesion and the microbiological detection of mycobacterium tuberculosis. stool cultures have recently been described as a useful tool in the diagnosis of atypical forms of tuberculosis. in this report, we describe the first case in the literature of laryngeal tuberculosis diagnosed by culture of stool samples. | 2015 | 25886183 |
| contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of mycobacterium tuberculosis infection in hiv-infected patients: comparison with the tuberculin skin test and the quantiferon-tb gold in-tube. | the screening and treatment of latent tuberculosis (tb) infection reduces the risk of progression to active disease and is currently recommended for hiv-infected patients. the aim of this study is to evaluate, in a low tb incidence setting, the potential contribution of an interferon-gamma release assay in response to the mycobacterial latency antigen heparin-binding haemagglutinin (hbha-igra), to the detection of mycobacterium tuberculosis infection in hiv-infected patients. | 2015 | 25886172 |
| mycobacterium tuberculosis antigen expression in cerebrospinal fluid monocytes. | 2015 | 25885160 | |
| mouse mincle: characterization as a model for human mincle and evolutionary implications. | mincle, the macrophage-inducible c-type lectin also known as clec-4e, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for mycobacterium tuberculosis and other pathogenic mycobacterial species. studies of the biological functions of human mincle often rely on mouse models, based on the assumption that the biological properties of the mouse receptor mimic those of the human protein. experimental support for this assumption has b ... | 2015 | 25884549 |
| implementing a large-scale systematic tuberculosis screening program in correctional facilities in south africa. | background. tuberculosis (tb) prevalence is high in correctional facilities in southern africa. with support from local south african nongovernmental organizations, the south african department of correctional services initiated a program of systematically screening newly admitted and current inmates for symptoms followed by genexpert mycobacterium tuberculosis (mtb)/rifampicin (rif) for microbiologic testing of symptomatic inmates. methods. we conducted a program evaluation during a 5-month w ... | 2015 | 25884008 |
| 2-substituted 6-(het)aryl-7-deazapurine ribonucleosides: synthesis, inhibition of adenosine kinases, and antimycobacterial activity. | a series of 6-(hetero)aryl- or 6-methyl-7-deazapurine ribonucleosides bearing a substituent at position 2 (cl, f, nh2, or ch3) were prepared by cross-coupling reactions at position 6 and functional group transformations at position 2. cytostatic, antiviral, and antimicrobial activity assays were performed. the title compounds were observed to be potent and selective inhibitors of mycobacterium tuberculosis adenosine kinase (adk), but not human adk; moreover, they were found to be non-cytotoxic. ... | 2015 | 25882678 |
| structure and function of rnase as: a novel virulence factor from mycobacterium tuberculosis. | the 3'-ends of both prokaryotic and eukaryotic rna can be polyadenylated and the effect of polyadenylation is known to increase the stability of transcripts in eukaryotes, whereas it promotes instability in prokaryotes. rnas are considered as key effectors of virulence mechanisms, since they are directly involved in regulatory pathways in pathogenic bacteria. deadenylation of rna is thus an important control point and rate-limiting step of its turnover. rnase as is a novel identified protein of ... | 2015 | 25882544 |
| icos and bcl6-dependent pathways maintain a cd4 t cell population with memory-like properties during tuberculosis. | immune control of persistent infection with mycobacterium tuberculosis (mtb) requires a sustained pathogen-specific cd4 t cell response; however, the molecular pathways governing the generation and maintenance of mtb protective cd4 t cells are poorly understood. using mhcii tetramers, we show that mtb-specific cd4 t cells are subject to ongoing antigenic stimulation. despite this chronic stimulation, a subset of pd-1(+) cells is maintained within the lung parenchyma during tuberculosis (tb). whe ... | 2015 | 25918344 |
| cd8 t cells and mycobacterium tuberculosis infection. | tuberculosis is primarily a respiratory disease that is caused by mycobacterium tuberculosis. m. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas. there is substantial evidence for the importance of cd4 t cells in control of tuberculosis, but the evidence for a requirement for cd8 t cells in this infection has not been proven in humans. however, animal model data support a non-redundant role for cd8 t cells in control of m. ... | 2015 | 25917388 |
| microrna-125a inhibits autophagy activation and antimicrobial responses during mycobacterial infection. | micrornas (mirnas) are small noncoding nucleotides that play critical roles in the regulation of diverse biological functions, including the response of host immune cells. autophagy plays a key role in activating the antimicrobial host defense against mycobacterium tuberculosis. although the pathways associated with autophagy must be tightly regulated at a posttranscriptional level, the contribution of mirnas and whether they specifically influence the activation of macrophage autophagy during m ... | 2015 | 25917095 |
| investigation and conformational analysis of fluorinated nucleoside antibiotics targeting siderophore biosynthesis. | antibiotic resistance represents one of the greatest threats to public health. the adenylation inhibitor 5'-o-[n-(salicyl)sulfamoyl]adenosine (sal-ams) is the archetype for a new class of nucleoside antibiotics that target iron acquisition in pathogenic microorganisms and is especially effective against mycobacterium tuberculosis, the causative agent of tuberculosis. strategic incorporation of fluorine at the 2' and 3' positions of the nucleoside was performed by direct fluorination to enhance a ... | 2015 | 25916415 |
| first crystal structures of mycobacterium tuberculosis 6-oxopurine phosphoribosyltransferase: complexes with gmp and pyrophosphate and with acyclic nucleoside phosphonates whose prodrugs have antituberculosis activity. | human tuberculosis is a chronic infectious disease affecting millions of lives. because of emerging resistance to current medications, new therapeutic drugs are needed. one potential new target is hypoxanthine-guanine phosphoribosyltransferase (mthgprt), a key enzyme of the purine salvage pathway. here, newly synthesized acyclic nucleoside phosphonates (anps) have been shown to be competitive inhibitors of mthgprt with ki values as low as 0.69 μm. prodrugs of these compounds arrest the growth of ... | 2015 | 25915781 |
| modified proofreading pcr for detection of point mutations, insertions and deletions using a ddntp-blocked primer. | the development of simple, accurate, rapid and cost-effective technologies for mutation detection is crucial to the early diagnosis and prevention of numerous genetic diseases, pharmacogenetics, and drug resistance. proofreading pcr (pr-pcr) was developed for mutation detection in 1998 but is rarely applied due to its low efficiency in allele discrimination. here we developed a modified pr-pcr method using a ddntp-blocked primer and a mixture of dna polymerases with and without the 3'-5' proofre ... | 2015 | 25915410 |
| regulation of l-type voltage gated calcium channel cacna1s in macrophages upon mycobacterium tuberculosis infection. | we demonstrated earlier the inhibitory role played by voltage gated calcium channels (vgccs) in regulating mycobacterium tuberculosis (m. tb) survival and pathogenesis. in this report, we investigated mechanisms and key players that regulate the surface expression of vgcc-cacna1s by rv2463 and m. tb infection in macrophages. our earlier work identified rv2463 to be expressed at early times post infection in macrophages that induced suppressor responses to dendritic cells and macrophages. our res ... | 2015 | 25915405 |