| enhanced cellular uptake of a new, in silico identified antitubercular candidate by peptide conjugation. | mycobacterium tuberculosis is a successful pathogen, and it can survive in infected macrophages in dormant phase for years and decades. the therapy of tuberculosis takes at least six months, and the slow-growing bacterium is resistant to many antibiotics. the development of novel antimicrobials to counter the emergence of bacteria resistant to current therapies is urgently needed. in silico docking methods and structure-based drug design are useful bioinformatics tools for identifying new agents ... | 2012 | 22515329 |
| the genotype® mtbdrplus assay for detection of drug resistance in mycobacterium tuberculosis in sweden. | the performance of the genotype(®) mtbdrplus assay was compared with conventional drug susceptibility testing (dst) in 604 patients with tuberculosis. the study comprised 477 mycobacterium tuberculosis complex isolates and 127 preparations of dna from clinical specimens which had been tested positive for m. tuberculosis by cobas(®)taqman(®) 48. by dst, isoniazid (inh) monoresistance was diagnosed in 56 (9.3%), rifampicin (rmp) monoresistance in 2 (0.3%) and multidrug resistance (mdr) in 21 (3.5% ... | 2012 | 22515295 |
| [recent advances in tuberculosis immunity]. | primary tuberculosis infection is acquired by the inhalation of droplets containing mycobacterium tuberculosis (mtb) bacilli. only 5-10% of those individuals infected by mtb develop clinical diseases, and disease presentation itself is heterogeneous, suggesting that host factors play a large role in disease susceptibility. protective immunity in the lung against mtb consist of the innate immunity in which alveolar macrophages play an central role, and the acquired immunity including various type ... | 2012 | 22514942 |
| [molecular epidemiology of rifampicin mono-resistant mycobacterium tuberculosis]. | we aimed to investigate the prevalence and possible transmission routes of rifampicin (rfp) mono-resistant mycobacterium tuberculosis strains. | 2012 | 22514938 |
| utility of interferon-γ release assay results to monitor anti-tubercular treatment in adults and children. | interferon-γ release assays (igras), including the commercially available t-spot.tb, quantiferon-tb gold (qft-g), and quantiferon-tb gold in-tube (qtf-g-it), enable detection of circulating t lymphocytes responsive to specific mycobacterium tuberculosis antigens. studies of the potential role of serial igras for assessment of response to anti-tubercular therapy are accumulating. | 2012 | 22512899 |
| prevalence, distribution and functional significance of the -237c to t polymorphism in the il-12rβ2 promoter in indian tuberculosis patients. | cytokine/cytokine receptor gene polymorphisms related to structure/expression could impact immune response. hence, the -237 polymorphic site in the 5' promoter region of the il-12rβ2 (snp id: rs11810249) gene associated with the ap-4 transcription motif gagctg, was examined. amplicons encompassing the polymorphism were generated from 46 pulmonary tuberculosis patients, 35 family contacts and 28 miscellaneous volunteers and sequenced. the c allele predominated among patients, (93.4%, 43/46), and ... | 2012 | 22509293 |
| diagnosing pulmonary tuberculosis with the xpert mtb/rif test. | tuberculosis (tb) due to mycobacterium tuberculosis (mtb) remains a major public health issue: the infection affects up to one third of the world population(1), and almost two million people are killed by tb each year. universal access to high-quality, patient-centered treatment for all tb patients is emphasized by who's stop tb strategy. the rapid detection of mtb in respiratory specimens and drug therapy based on reliable drug resistance testing results are a prerequisite for the successful im ... | 2012 | 22508485 |
| molecular strain typing of mycobacterium tuberculosis complex in bamako, mali. | to identify strains of mycobacterium tuberculosis complex (mtc) circulating in bamako and to examine the relationship between the strains and their drug susceptibility profiles. | 2012 | 22508197 |
| diagnostic sensitivity of culture and drug resistance patterns in korean patients with intestinal tuberculosis. | it is challenging to differentiate between intestinal tuberculosis (itb) and crohn's disease in areas where tb is still prevalent. the use of diagnostic tools and verifying the drug resistance patterns of itb can be helpful for its correct diagnosis. | 2012 | 22508109 |
| mycobacterium tuberculosis manlam inhibits t-cell-receptor signaling by interference with zap-70, lck and lat phosphorylation. | immune evasion is required for mycobacterium tuberculosis to survive in the face of robust cd4(+) t cell responses. we have shown previously that m. tuberculosis cell wall glycolipids, including mannose capped lipoarabinomannan (manlam), directly inhibit polyclonal murine cd4(+) t cell activation by blocking zap-70 phosphorylation. we extended these studies to antigen-specific murine cd4(+) t cells and primary human t cells and found that manlam inhibited them as well. lck and lat phosphorylatio ... | 2016 | 22507872 |
| trends in the epidemiology of childhood tuberculosis in greece. | a hospital referral center for childhood tuberculosis (tb). | 2012 | 22507870 |
| alternative sputum preparation to improve polymerase chain reaction assay for mycobacterium tuberculosis detection. | tuberculosis (tb), one of the major airborne infectious bacterial diseases, remains an important health problem worldwide. it is estimated that there are 1700 new cases per year in santa catarina state, brazil. | 2012 | 22507521 |
| breath analysis as a potential diagnostic tool for tuberculosis. | cape town, south africa. | 2012 | 22507235 |
| molecular analysis of isoniazid-resistant mycobacterium tuberculosis isolates in uruguay. | the incidence of tuberculosis (tb) is increasing in high-risk populations in uruguay, possibly owing to emerging resistance. mycobacterial interspersed repetitive units (miru) genotyping and katg sequence analysis of isoniazid (inh) resistance-associated mutations were performed in 45 inh-resistant mycobacterium tuberculosis isolates in uruguayan patients. the genotype distribution among inh-resistant isolates shares features of that of neighbouring countries, with a predominance of latin americ ... | 2012 | 22507192 |
| synthesis, structure-activity relationship and in vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives. | twenty-eight new 13-n-octylberberine derivatives were synthesized and evaluated for their activities against drug-susceptible mycobacterium tuberculosis (m. tuberculosis) strain h(37)rv. among these compounds, compound 16e was the most effective anti-tubercular agent with a mic value of 0.125 μg/ml. importantly, compound 16e exhibited more potent effect against rifampicin (rif)- and isoniazid (inh)-resistant m. tuberculosis strains than both rif and inh, suggesting a new mechanism of action. the ... | 2012 | 22503208 |
| comparative analysis of mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints. | mycobacterium tuberculosis complex (mtbc) genomes contain 2 large gene families termed pe and ppe. the function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. using comparative sequence analysis of 18 publicly available mtbc whole genome sequences, we have performed ... | 2012 | 22496726 |
| regulation of mycobacterium tuberculosis-dependent hiv-1 transcription reveals a new role for nfat5 in the toll-like receptor pathway. | tuberculosis (tb) disease in hiv co-infected patients contributes to increased mortality by activating innate and adaptive immune signaling cascades that stimulate hiv-1 replication, leading to an increase in viral load. here, we demonstrate that silencing of the expression of the transcription factor nuclear factor of activated t cells 5 (nfat5) by rna interference (rnai) inhibits mycobacterium tuberculosis (mtb)-stimulated hiv-1 replication in co-infected macrophages. we show that nfat5 gene a ... | 2012 | 22496647 |
| neutrophils promote mycobacterial trehalose dimycolate-induced lung inflammation via the mincle pathway. | trehalose 6,6'-dimycolate (tdm), a cord factor of mycobacterium tuberculosis (mtb), is an important regulator of immune responses during mtb infections. macrophages recognize tdm through the mincle receptor and initiate tdm-induced inflammatory responses, leading to lung granuloma formation. although various immune cells are recruited to lung granulomas, the roles of other immune cells, especially during the initial process of tdm-induced inflammation, are not clear. in this study, mincle signal ... | 2012 | 22496642 |
| consistency of mycobacterium tuberculosis-specific interferon-gamma responses in hiv-1-infected women during pregnancy and postpartum. | we determined the consistency of positive interferon-gamma (ifn-γ) release assays (igras) to detect latent tb infection (ltbi) over one-year postpartum in hiv-1-infected women. | 2012 | 22496602 |
| tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities. | tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued mycobacterium tuberculosis transmission within communities. currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be neces ... | 2012 | 22496353 |
| the risk of tuberculosis in transplant candidates and recipients: a tbnet consensus statement. | tuberculosis (tb) is a possible complication of solid organ and hematopoietic stem cell transplantation. the identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with mycobacterium tuberculosis from progressing to active disease. the best available proxy for diagnosing latent infection with m. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-γ base ... | 2012 | 22496318 |
| interaction between hiv and mycobacterium tuberculosis: hiv-1-induced cd4 t-cell depletion and the development of active tuberculosis. | hiv infection is the main driver of the hiv/tuberculosis (tb) syndemic in southern africa since the early 1990s, when hiv infection rates started to increase exponentially and tb incidence rates quadruplet simultaneously. here, we discuss pathogenic mechanisms of hiv-induced cd4 t-cell depletion and their potential impact on immune control of mycobacterium tuberculosis. | 2012 | 22495739 |
| performance of the roche lightcycler real-time pcr assay for diagnosing extrapulmonary tuberculosis. | the roche lightcycler mycobacterium detection molecular assay for mycobacterium tuberculosis, m. avium, and m. kansasii, was applied to tissue specimens. it performed well on lymph node and cerebrospinal fluid specimens and less well on lung, liver, and bone marrow core biopsy specimens, but used in conjunction with a clinical suspicion of tuberculosis, it could augment patient management. | 2012 | 22495565 |
| contribution of efflux to the emergence of isoniazid and multidrug resistance in mycobacterium tuberculosis. | multidrug resistant (mdr) tuberculosis is caused by mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a mdr phenotype. the study was based on the in vitro induction of an isoniazid resistant phenotype by prolonged serial exposure ... | 2012 | 22493700 |
| uptake and accumulation of oxidized low-density lipoprotein during mycobacterium tuberculosis infection in guinea pigs. | the typical host response to infection of humans and some animals by m. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. in previous studies we showed that infection of immunologically naïve guinea pigs with m. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondial ... | 2012 | 22493658 |
| innate and adaptive immune responses during acute m. tuberculosis infection in adult household contacts in kampala, uganda. | contacts of active pulmonary tuberculosis (tb) patients are at risk for mycobacterium tuberculosis (mtb) infection. because most infections are controlled, studies during mtb infection provide insight into protective immunity. we compared immune responses of adult household contacts that did and did not convert the tuberculin skin test (tst). innate and adaptive immune responses were measured by whole blood assay. responses of tst converters (tstc) were compared with persistently tst negative co ... | 2012 | 22492155 |
| training laboratory technicians from the ethiopian periphery in the mods technique enables rapid and low-cost diagnosis of mycobacterium tuberculosis infection. | tuberculosis (tb) is a leading cause of morbidity and mortality and is frequently complicated by emergence of drug-resistant strains. diagnosis of tb in developing countries is often based on the relatively insensitive acid-fast staining that does not enable susceptibility profiling. microscopic observation drug susceptibility assay (mods) is an inexpensive, simple method that enables rapid tb culture coupled with susceptibility testing. a 3-week mods training of three ethiopian laboratory techn ... | 2012 | 22492154 |
| current understanding of the immune response to tuberculosis in children. | even in the era of promising molecular diagnostics for tuberculosis, understanding of the immune response remains urgent and fundamental to combating paediatric tuberculosis, given its paucibacillary nature. | 2012 | 22491144 |
| [time course of interleukin-21 and related cytokines expression in rats with experimental autoimmune myocarditis]. | to observe the time course of interleukin (il)-21 and related cytokines expression in rats with experimental autoimmune myocarditis (eam). | 2012 | 22490633 |
| [meta analysis on the correlation between mycobacterium tuberculosis beijing family strains and drug resistance]. | to explore the correlation between beijing genotype (beijing family) strains of mycobacterium tuberculosis (mtb) and drug resistance. | 2012 | 22490200 |
| symptom screen for identification of highly infectious tuberculosis in people living with hiv in southeast asia. | tuberculosis (tb) is the leading cause of death among people living with hiv and frequently transmitted among this susceptible group. transmission can be reduced by infection control practices. simple evidence-based methods to identify patients who should be isolated are not well described in the literature. we sought to identify a simple, sensitive symptom or symptom combination that healthcare providers in resource-limited settings can use to identify and isolate persons living with hiv with h ... | 2012 | 22487587 |
| interferon-gamma release assays for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. | interferon -gamma release assays (igras) provide a new diagnostic method for mycobacterium tuberculosis (tb) infection. however, the diagnostic value of igras for extrapulmonary tb (eptb) has not been clarified. we searched several databases and selected papers with strict inclusion criteria, evaluated the evidence of commercially available igras (quantiferon(®) -tb gold qft-g or qft-git and t-spot(®) .tb) on blood and the tuberculin skin test (tst) using random effects models. twenty studies wi ... | 2012 | 22487051 |
| proteomic analysis of sputum in patients with active pulmonary tuberculosis. | the protein composition of sputum most faithfully reflects the state of the lungs. the aim of this study was to determine whether relative qualitative and quantitative differences in protein expression of sputum could be related to active pulmonary tuberculosis. sputum samples were collected from 65 patients with active pulmonary tuberculosis and 38 healthy controls. comprehensive proteomic approaches were used to profile the proteome changes of host sputum in response to mycobacterium tuberculo ... | 2012 | 22486982 |
| frosted branch angiitis in a woman with mycobacterium tuberculosis infection. | to describe a case of frosted branch angiitis in a patient with tuberculous meningitis. | 2012 | 22486266 |
| quantitative polymerase chain reaction for mycobacterium tuberculosis in so-called eales' disease. | to report mycobacterial load in the vitreous of patients labeled as having eales' disease. | 2012 | 22486260 |
| immunosurveillance for mycobacterium tuberculosis of health care personnel in a third level care hospital. | health care workers are at risk for mycobacterium tuberculosis (mtb) infection. | 2013 | 22486073 |
| annotation of the m. tuberculosis hypothetical orfeome: adding functional information to more than half of the uncharacterized proteins. | the genome of mycobacterium tuberculosis (h37rv) contains 4,019 protein coding genes, of which more than thousand have been categorized as 'hypothetical' implying that for these not even weak functional associations could be identified so far. we here predict reliable functional indications for half of this large hypothetical orfeome: 497 genes can be annotated based on orthology, and another 125 can be linked to interacting proteins via integrated genomic context analysis and literature mining. ... | 2012 | 22485162 |
| primary tuberculosis of the oral cavity. | there is a well-known phrase that states, "the more things change, the more they stay the same." this expression continues to apply to tuberculosis (tb), a widespread infectious disease traced back to the earliest of centuries. tb has claimed its victims throughout much of known human history. mycobacterium tuberculosis may have killed more persons than any other microbial pathogen and is one of the major causes of ill health and death worldwide. although the overall incidence of tb has decrease ... | 2012 | 22484880 |
| in silico identification of potential antigenic proteins and promiscuous ctl epitopes in mycobacterium tuberculosis. | cell-mediated immunity is critical for the control of mycobacterium tuberculosis infection. we hypothesized that those proteins of m. tuberculosis (mtb) that do not have homologs in humans as well as human gut flora, would mount a good antigenic response in man, and employed a bioinformatics approach to identify mtb antigens capable of inducing a robust cell-mediated immune response in humans. in the first step we identified 624 mtb proteins that had no homologs in humans. comparison of this set ... | 2012 | 22484107 |
| chemical synthesis and biological evaluation of triazole derivatives as inhibitors of inha and antituberculosis agents. | a series of triazoles have been prepared and evaluated as inhibitors of inha as well as inhibitors of mycobacterium tuberculosis h(37)r(v). several of these new compounds possess a good activity against inha, particularly compounds 17 and 18 for which molecular docking has been performed. concerning their activities against m. tuberculosis h(37)r(v) strain, two of them, 3 and 12, were found to be good inhibitors with mic values of 0.50 and 0.25 μg/ml, respectively. particularly, compound 12 pres ... | 2012 | 22483635 |
| iron sulfur cluster proteins and microbial regulation: implications for understanding tuberculosis. | all pathogenic and nonpathogenic microbes are continuously exposed to environmental or endogenous reactive oxygen and nitrogen species, which can critically effect survival and disease. iron-sulfur [fe-s] cluster containing prosthetic groups provide the microbial cell with a unique capacity to sense and transcriptionally respond to diatomic gases (e.g. no and o2) and redox-cycling agents. recent advances in our understanding of the mechanisms for how the fnr and soxr [fe-s] cluster proteins resp ... | 2012 | 22483328 |
| antioxidant, antitubercular and cytotoxic activities of piper imperiale. | phenolic compounds are widely distributed in nature and act as pharmacologically active constituents in many herbal medicines. they have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. in the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken. the total phenol content ranged from 1.98 to 6.94 mg gae/gdw among ... | 2012 | 22481537 |
| cd4 t cell depletion exacerbates acute mycobacterium tuberculosis while reactivation of latent infection is dependent on severity of tissue depletion in cynomolgus macaques. | cd4 t cells are believed to be important in protection against mycobacterium tuberculosis, but the relative contribution to control of initial or latent infection is not known. antibody-mediated depletion of cd4 t cells in m. tuberculosis-infected cynomolgus macaques was used to study the role of cd4 t cells during acute and latent infection. anti-cd4 antibody severely reduced levels of cd4 t cells in blood, airways, and lymph nodes. increased pathology and bacterial burden were observed in cd4- ... | 2012 | 22480184 |
| genetic diversity of mycobacterium tuberculosis isolates from tibetans in tibet, china. | tuberculosis (tb) is a serious health problem in tibet where tibetans are the major ethnic group. although genotyping of mycobacterium tuberculosis (m. tuberculosis) isolates is a valuable tool for tb control, our knowledge of population structure of m. tuberculosis circulating in tibet is limited. | 2012 | 22479472 |
| estimating fitness by competition assays between drug susceptible and resistant mycobacterium tuberculosis of predominant lineages in mumbai, india. | multi drug resistant tuberculosis (mdr tb) is a threat to global tuberculosis control. a significant fitness cost has been associated with dr strains from specific lineages. evaluation of the influence of the competing drug susceptible strains on fitness of drug resistant strains may have an important bearing on understanding the spread of mdr tb. the aim of this study was to evaluate the fitness of mdr tb strains, from a tb endemic region of western india: mumbai, belonging to 3 predominant lin ... | 2012 | 22479407 |
| evaluation of genetic mutations associated with mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review. | rapid molecular diagnostics for detecting multidrug-resistant and extensively drug-resistant tuberculosis (m/xdr-tb) primarily identify mutations in mycobacterium tuberculosis (mtb) genes associated with drug resistance. their accuracy, however, is dependent largely on the strength of the association between a specific mutation and the phenotypic resistance of the isolate with that mutation, which is not always 100%. while this relationship is well established and reliable for first-line anti-tb ... | 2012 | 22479378 |
| virulence regulator espr of mycobacterium tuberculosis is a nucleoid-associated protein. | the principal virulence determinant of mycobacterium tuberculosis (mtb), the esx-1 protein secretion system, is positively controlled at the transcriptional level by espr. depletion of espr reportedly affects a small number of genes, both positively or negatively, including a key esx-1 component, the espacd operon. espr is also thought to be an esx-1 substrate. using espr-specific antibodies in chip-seq experiments (chromatin immunoprecipitation followed by ultra-high throughput dna sequencing) ... | 2012 | 22479184 |
| combining cheminformatics methods and pathway analysis to identify molecules with whole-cell activity against mycobacterium tuberculosis. | new strategies for developing inhibitors of mycobacterium tuberculosis (mtb) are required in order to identify the next generation of tuberculosis (tb) drugs. our approach leverages the integration of intensive data mining and curation and computational approaches, including cheminformatics combined with bioinformatics, to suggest biological targets and their small molecule modulators. | 2012 | 22477069 |
| case of mycobacterium tuberculosis meningitis: gram staining as a useful initial diagnostic clue for tuberculous meningitis. | a 32-year-old man was admitted to our hospital because of fever, headache, and loss of consciousness. four days before admission, he had had difficulty speaking. on the day of admission, his colleague had found him to be unconscious and lying on his back. he was admitted to our hospital. the temperature at the eardrum was 35.2°c. neurologic evaluation was negative. computed tomography (ct) scan of the brain showed slight ventricular enlargement bilaterally. an x-ray film of the chest showed no a ... | 2012 | 22476652 |
| synthesis and characterization of pyruvate-isoniazid analogs and their copper complexes as potential icl inhibitors. | currently used anti-tubercular drugs target actively growing mycobacterium tuberculosis (mtb) but there are no current therapies targeting persistent mycobacteria. isocitrate lyase (icl) is an important enzyme of the glyoxylate shunt pathway used by mtb for sustaining intracellular infection in inflammatory macrophages under conditions of stress such as nutrient depletion and anaerobic metabolism. since the humans do not possess this enzyme it constitutes an attractive target for selective drug ... | 2012 | 22475559 |
| risk of tuberculosis reactivation with tofacitinib (cp-690550). | individuals with latent tuberculosis infection (ltbi) live with a risk of reactivation, and several treatments for chronic inflammatory conditions are highly associated with such reactivation. a new janus kinase inhibitor, tofacitinib (cp-690550), has shown promising results for treatment of inflammatory disorders, thus raising concerns of risk of active tuberculosis. our goal was to characterize the impact of tofacitinib on ltbi using a mouse model of contained tuberculosis. our data indicate t ... | 2012 | 22474037 |
| il-2 simultaneously expands foxp3+ t regulatory and t effector cells and confers resistance to severe tuberculosis (tb): implicative treg-t effector cooperation in immunity to tb. | the possibility that simultaneous expansion of t regulatory cells (treg) and t effector cells early postinfection can confer some immunological benefits has not been studied. in this study, we tested the hypothesis that early, simultaneous cytokine expansion of treg and t effector cells in a tissue infection site can allow these t cell populations to act in concert to control tissue inflammation/damage while containing infection. il-2 treatments early after mycobacterium tuberculosis infection o ... | 2012 | 22474020 |
| synthesis and in vitro anti-tubercular evaluation of 1,2,3-triazole tethered β-lactam-ferrocene and β-lactam-ferrocenylchalcone chimeric scaffolds. | twenty different triazoles were prepared to probe the anti-tubercular structure-activity relationships (sar) within the β-lactam-ferrocene-triazole conjugate family. the compounds have been synthesized by copper-catalyzed "click chemistry". in vitro anti-tubercular activity was determined for each compound but the synthesized hybrids failed to inhibit mycobacterium tuberculosis growth even at high doses. the manuscript assumes significance as this is the first report on the inclusion of ferrocen ... | 2012 | 22473422 |
| simultaneous occurrence of papulonecrotic tuberculid and erythema induratum in a patient with pulmonary tuberculosis. | although papulonecrotic tuberculid is an uncommon cutaneous manifestation of tuberculosis (tb) associated with mycobacterium tuberculosis infection, the simultaneous occurrence of papulonecrotic tuberculid and erythema induratum is even rarer. papulonecrotic tuberculid occurs predominantly in young adults and is characterized by eruptions of necrotizing papules that heal with varioliform scars. histopathologic findings include wedge-shaped necrosis of the dermis, poorly formed granulomatous infi ... | 2013 | 22472030 |
| synthesis, characterization and in-vitro antitubercular activity of isoniazid-gelatin conjugate. | a novel and simple method to synthesize antitubercular-protein conjugate by solid phase synthesis was developed employing a carboxypolystyrene resin. the aim was to covalently bind a drug with antitubercular activity, isoniazid, to a biomacromolecule, gelatin, widely used in the pharmaceutical, cosmetic and food industry. | 2012 | 22471367 |
| [accidental discoveries, different mechanisms of action. active agents against mycobacterium tuberculosis in clinical application]. | | 2012 | 22470917 |
| fusion of the mycobacterium tuberculosis antigen 85a to an oligomerization domain enhances its immunogenicity in both mice and non-human primates. | to prevent important infectious diseases such as tuberculosis, malaria and hiv, vaccines inducing greater t cell responses are required. in this study, we investigated whether fusion of the m. tuberculosis antigen 85a to recently described adjuvant imx313, a hybrid avian c4bp oligomerization domain, could increase t cell responses in pre-clinical vaccine model species. in mice, the fused antigen 85a showed consistent increases in cd4(+) and cd8(+) t cell responses after dna and mva vaccination. ... | 2012 | 22470455 |
| a genome-wide identification analysis of small regulatory rnas in mycobacterium tuberculosis by rna-seq and conservation analysis. | we propose a new method for smallrnas (srnas) identification. first we build an effective target genome (etg) by means of a strand-specific procedure. then we propose a new bioinformatic pipeline based mainly on the combination of two types of information: the first provides an expression map based on rna-seq data (reads map) and the second applies principles of comparative genomics leading to a conservation map. by superimposing these two maps, a robust method for the search of srnas is obtaine ... | 2012 | 22470422 |
| effect of mutation and genetic background on drug resistance in mycobacterium tuberculosis. | bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (tb). only a few studies have reported on the interactions between different bacterial factors. we studied drug-resistant mycobacterium tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in switzerland. we determined quantitative drug resistance levels of first-line drugs by using bactec mgit-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant ... | 2012 | 22470121 |
| effect of coadministration of moxifloxacin and rifampin on mycobacterium tuberculosis in a murine aerosol infection model. | coadministration of moxifloxacin and rifampin was evaluated in a murine model of mycobacterium tuberculosis pulmonary infection to determine whether the finding of antagonism documented in a hollow-fiber infection model could be recapitulated in vivo. colony counts were followed in a no-treatment control group, groups administered moxifloxacin or rifampin monotherapy, and a group administered a combination of the two agents. following 18 days of once-daily oral administration to mice infected wi ... | 2012 | 22470118 |
| influence of antituberculosis drug resistance and mycobacterium tuberculosis lineage on outcome in hiv-associated tuberculous meningitis. | hiv-associated tuberculous meningitis (tbm) has high mortality. aside from the devastating impact of multidrug resistance (mdr) on survival, little is understood about the influence of other bacterial factors on outcome. this study examined the influence of mycobacterium tuberculosis drug resistance, bacterial lineage, and host vaccination status on outcome in patients with hiv-associated tbm. mycobacterium tuberculosis isolates from the cerebrospinal fluid of 186 patients enrolled in two studie ... | 2012 | 22470117 |
| sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis. | novel oral regimens composed of new drugs with potent activity against mycobacterium tuberculosis and no cross-resistance with existing agents are needed to shorten and simplify treatment for both drug-susceptible and drug-resistant tuberculosis. as part of a continuing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. in the first experiment, several 3- and 4-drug combinations containing new ag ... | 2012 | 22470112 |
| substituted aminopyrimidine protein kinase b (pknb) inhibitors show activity against mycobacterium tuberculosis. | a high-throughput screen against pknb, an essential serine-threonine protein kinase present in mycobacterium tuberculosis (m. tuberculosis), allowed the identification of an aminoquinazoline inhibitor which was used as a starting point for sar investigations. although a significant improvement in enzyme affinity was achieved, the aminoquinazolines showed little or no cellular activity against m. tuberculosis. however, switching to an aminopyrimidine core scaffold and the introduction of a basic ... | 2012 | 22469702 |
| drug susceptibility of mycobacterium tuberculosis beijing genotype and association with mdr tb. | to determine differences in the ability of mycobacterium tuberculosis strains to withstand antituberculosis drug treatment, we compared the activity of antituberculosis drugs against susceptible beijing and east-african/indian genotype m. tuberculosis strains. beijing genotype strains showed high rates of mutation within a wide range of drug concentrations, possibly explaining this genotype's association with multidrug-resistant tuberculosis. | 2012 | 22469099 |
| characterization of mycobacterium orygis as m. tuberculosis complex subspecies. | the oryx bacilli are mycobacterium tuberculosis complex organisms for which phylogenetic position and host range are unsettled. we characterized 22 isolates by molecular methods and propose elevation to subspecies status as m. orygis. m. orygis is a causative agent of tuberculosis in animals and humans from africa and south asia. | 2012 | 22469053 |
| screening for latent infection with mycobacterium tuberculosis: a plea for targeted testing in low endemic regions. | the higher specificity proposed for ifn-γ-release assays (igras) compared with tuberculin skin testing (tst) may indicate superiority in identifying patients at risk for progression towards active tuberculosis. unfortunately, available assays may frequently show discordant results. to aid in interpreting discordant results, the article under evaluation has comparatively analyzed results of the tst and two commercially available igras in a low-risk population for tuberculosis. tst-positive/igra-n ... | 2012 | 22468813 |
| design, synthesis and in vivo/in vitro screening of novel chlorokojic acid derivatives. | a series of novel mannich bases of chlorokojic acid (2-chloromethyl-5-hydroxy-4h-pyran-4-one) were synthesized and their biological activities were investigated. anticonvulsant activity results according to phase-i tests of antiepileptic drug development (add) program revealed that compound 13 was the most effective one at 4 h against subcutaneous pentylenetetrazole (scptz)-induced seizure test. antimicrobial activities were evaluated in vitro against bacteria and fungi by using broth microdilut ... | 2013 | 22468745 |
| important role for mycobacterium tuberculosis uvrd1 in pathogenesis and persistence apart from its function in nucleotide excision repair. | mycobacterium tuberculosis survives and replicates in macrophages, where it is exposed to reactive oxygen and nitrogen species that damage dna. in this study, we investigated the roles of uvra and uvrd1, thought to be parts of the nucleotide excision repair pathway of m. tuberculosis. strains in which uvrd1 was inactivated either alone or in conjunction with uvra were constructed. inactivation of uvrd1 resulted in a small colony phenotype, although growth in liquid culture was not significantly ... | 2012 | 22467787 |
| discordant drug susceptibility for mycobacterium tuberculosis within families. | children with presumed tuberculosis who are in contact with a multidrug-resistant source case should be treated according to the drug susceptibility of the source case's isolate. however, it is important to obtain a microbiologic diagnosis as it is possible for the child to have a different susceptibility profile to the source case. we present 2 such cases. | 2012 | 22466320 |
| mycobacterium tuberculosis whib1 represses transcription of the essential chaperonin groel2. | a central feature of tb pathogenesis is the formation of mycobacterium tuberculosis latent infections that can persist for decades. nitric oxide produced by infected lung macrophages promotes expression of genes associated with dormancy, and impaired nitric oxide production can lead to reactivation of latent disease. recently, whib1 was identified as a nitric oxide-responsive transcription factor. here it is shown that apo-whib1 binds to groel2 (rv0440) promoter dna. apo-whib1 inhibited transcri ... | 2012 | 22464736 |
| surgical treatment of thoracic pott disease in a 3-year-old child, with vertebral column resection and posterior-only circumferential reconstruction of the spinal column: case report. | tuberculosis (tb) is a common disease worldwide that is caused by mycobacterium tuberculosis. tuberculosis of the spine, also called pott disease, is the most common site of bony dissemination. although children are disproportionately affected, spinal tb is nonetheless rare in very young children. cases involving infants requiring surgical intervention have been previously reported, and they are often associated with greater management challenges given the technical difficulty with instrumentati ... | 2012 | 22462713 |
| mycobacteria and the intraphagosomal environment: take it with a pinch of salt(s)! | ancient protozoan phagocytes and modern professional phagocytes of metazoans, such as macrophages, employ evolutionarily conserved mechanisms to kill microbes. these mechanisms rely on microbial ingestion, followed by maturation of the phagocytic vacuole, or so-called phagosome. phagosome maturation includes a series of fusion and fission events with the host cell endosomes and lysosomes, leading to a rapid increase of the degradative properties of the vacuole and to the destruction of the inges ... | 2012 | 22462580 |
| the effect of antituberculosis treatment on interferon-gamma release assay results. | monitoring the efficacy of antituberculosis therapy is crucial. the aim of this work is to investigate the effect of tuberculosis treatment on interferon-gamma response using quanti-feron-tb gold in tube (qft-git). | 2011 | 22462309 |
| detection of first- and second-line drug resistance in mycobacterium tuberculosis clinical isolates by pyrosequencing. | conventional phenotypic drug susceptibility testing (dst) methods for mycobacterium tuberculosis are laborious and very time-consuming. early detection of drug-resistant tuberculosis (tb) is essential for prevention and control of tb transmission. we have developed a pyrosequencing method for simultaneous detection of mutations associated with resistance to rifampin, isoniazid, ethambutol, amikacin, kanamycin, capreomycin, and ofloxacin. seven pyrosequencing assays were optimized for following l ... | 2012 | 22461677 |
| a novel tuberculosis dna vaccine in an hiv-1 p24 protein backbone confers protection against mycobacterium tuberculosis and simultaneously elicits robust humoral and cellular responses to hiv-1. | tuberculosis (tb) caused by mycobacterium tuberculosis remains a major infectious disease worldwide. moreover, latent m. tuberculosis infection is more likely to progress to active tb and eventually leads to death when hiv infection is involved. thus, it is urgent to develop a novel tb vaccine with immunogenicity to both m. tuberculosis and hiv. in this study, four uncharacterized t cell epitopes from mpt64, ag85a, ag85b, and tb10.4 antigens of m. tuberculosis were predicted, and hiv-1-derived p ... | 2012 | 22461526 |
| elucidation of mycobacterium tuberculosis type ii dehydroquinase inhibitors using a fragment elaboration strategy. | a library of novel mycobacterium tuberculosis type ii dehydroquinase (dhqase) inhibitors were discovered through the use of a fragment elaboration approach. putative active site binding fragments were initially assessed in silico which led to the selection of two small aromatic fragments for further investigation. synthetic elaboration of the fragments provided a library of 34 inhibitors that exhibited low-micromolar inhibition of type ii dhqase. a number of these inhibitors also showed antibact ... | 2012 | 22461418 |
| interaction of wild type, g68r and l125m isoforms of the arylamine-n-acetyltransferase from mycobacterium tuberculosis with isoniazid: a computational study on a new possible mechanism of resistance. | isoniazid (inh) is a front-line drug used in the treatment of tuberculosis (tb), a disease that remains a major cause of death worldwide. isoniazid is a prodrug, requiring activation in the mycobacterial cell by the catalase-peroxidase (cp) enzyme. recent studies have suggested that acetylation of inh by the arylamine-n-acetyltransferase from mycobacterium tuberculosis (tbnat) may be a possible cause of inactivation of the drug thus resulting in resistant strains. in this study, computational te ... | 2012 | 22460521 |
| sequencing-based detection of drug-resistant mycobacterium tuberculosis in patients with spinal tuberculosis. | traditionally, bacterial cultures serve as the gold standard for the detection of drug resistance and can provide evidence for directing the treatment of tuberculosis. however, this method has a low positive rate and is time consuming, which significantly limits its wide application. thus, in the present study, the genes associated with drug resistance were amplified and sequenced to determine the presence of drug-resistant mutations in mycobacterium tuberculosis. in addition, to find a more sen ... | 2012 | 22460350 |
| a novel asymmetric-loop molecular beacon-based two-phase hybridization assay for accurate and high-throughput detection of multiple drug resistance-conferring point mutations in mycobacterium tuberculosis. | the accurate and high-throughput detection of drug resistance-related multiple point mutations remains a challenge. although the combination of molecular beacons with bio-immobilization technology, such as microarray, is promising, its application is difficult due to the ineffective immobilization of molecular beacons on the chip surface. here, we propose a novel asymmetric-loop molecular beacon in which the loop consists of 2 parts. one is complementary to a target, while the other is complemen ... | 2012 | 22460100 |
| predict mycobacterial proteins subcellular locations by incorporating pseudo-average chemical shift into the general form of chou's pseudo amino acid composition. | mycobacterium tuberculosis (mtb) is a pathogenic bacterial species in the genus mycobacterium and the causative agent of most cases of tuberculosis (berman et al., 2000). knowledge of the localization of mycobacterial protein may help unravel the normal function of this protein. automated prediction of mycobacterial protein subcellular localization is an important tool for genome annotation and drug discovery. in this work, a benchmark data set with 638 non-redundant mycobacterial proteins is co ... | 2012 | 22459701 |
| molecular dynamics simulations of the coenzyme induced conformational changes of mycobacterium tuberculosis l-alanine dehydrogenase. | mycobacterium tuberculosis l-alanine dehydrogenase (l-mtaladh) catalyzes the nadh-dependent reversible oxidative deamination of l-alanine to pyruvate and ammonia. l-mtaladh has been proposed to be a potential target in the treatment of tuberculosis. based on the crystal structures of this enzyme, molecular dynamics simulations were performed to investigate the conformational changes of l-mtaladh induced by coenzyme nadh. the results show that the presence of nadh in the binding domain restricts ... | 2012 | 22459692 |
| fluorosugar chain termination agents as probes of the sequence specificity of a carbohydrate polymerase. | naturally occurring carbohydrate polymers are ubiquitous. they are assembled by polymerizing glycosyltransferases, which can generate polysaccharide products with repeating sequence patterns. the fidelity of enzymes of this class is unknown. we report a method for testing the fidelity of carbohydrate polymerase pattern deposition: we synthesized fluorosugar donors and used them as chain termination agents. the requisite nucleotide fluorosugars could be produced from a single intermediate using t ... | 2012 | 22458542 |
| translating basic science insight into public health action for multidrug- and extensively drug-resistant tuberculosis. | multidrug (mdr)- and extensively drug-resistant (xdr) tuberculosis (tb) impose a heavy toll of human suffering and social costs. controlling drug-resistant tb is a complex global public health challenge. basic science advances including elucidation of the genetic basis of resistance have enabled development of new assays that are transforming the diagnosis of mdr-tb. molecular epidemiological approaches have provided new insights into the natural history of tb with important implications for dru ... | 2012 | 22458269 |
| adjunct immunotherapies for tuberculosis. | the continued spread of multidrug-resistant (mdr) tuberculosis and extensively drug-resistant tuberculosis poses a major threat to global tuberculosis control. treatment is complex and requires longer use of more-expensive, less effective, and toxic anti-tuberculosis drugs, which results in high morbidity and mortality. the poor treatment outcomes and the slow progress in the development and evaluation of new tuberculosis drugs have given rise to the development of adjunct immunotherapy. the hos ... | 2012 | 22457298 |
| specific t cells restore the autophagic flux inhibited by mycobacterium tuberculosis in human primary macrophages. | autophagy inhibits survival of intracellular mycobacterium tuberculosis when induced by rapamycin or interferon γ (ifn-γ), but it remains unclear whether m. tuberculosis itself can induce autophagy and whether t cells play a role in m. tuberculosis-mediated autophagy. the aim of this study was to evaluate the impact of m. tuberculosis on autophagy in human primary macrophages and the role of specific t cells in this process. | 2012 | 22457295 |
| a functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis. | genetic variation influences susceptibility or resistance to tuberculosis. interleukin 6 (il-6) contributes to protection against tuberculosis in mice. however, its role in regulating susceptibility or resistance to tuberculosis in humans is unclear. | 2012 | 22457277 |
| tuberculous spondylitis presenting as severe chest pain. | this case report describes a 32-year-old male who presented to an emergency department with severe chest pain and a history of cough, fever, night sweats, loss of appetite and weight. chest radiography revealed a left upper lobe consolidation and multiple compression deformities in the thoracic spine. magnetic resonance imaging demonstrated significant kyphosis and vertebral plana at two thoracic levels. anterior compression of the spinal cord and adjacent soft tissue masses were also noted. | 2012 | 24765441 |
| antiprotozoal and antimycobacterial activities of pure compounds from aristolochia elegans rhizomes. | we analyzed the antimycobacterial activity of the hexane extract of rhizomes from aristolochia elegans. some compounds of this extract were purified and tested against a group of drug-resistant mycobacterium tuberculosis strains. we also evaluated their antiprotozoal activities. the hexane extract was active against m. tuberculosis h37rv at a mic = 100 μg ml(-1); the pure compounds eupomatenoid-1, fargesin, and (8r,8'r,9r)-cubebin were active against m. tuberculosis h37rv (mic = 50 μg ml(-1)), w ... | 2012 | 22454670 |
| mechanisms of delayed anti-tuberculosis protection in the lung of parenteral bcg-vaccinated hosts: a critical role of airway luminal t cells. | the immune mechanisms underlying unsatisfactory pulmonary mucosal protection by parenteral bacillus calmette-guérin (bcg) immunization remain poorly understood. we found that parenteral bcg immunization failed to elicit airway luminal t cells (alt) whereas it induced significant t cells in the lung interstitium. after mycobacterium tuberculosis (m.tb) challenge, alt remained missing for 10 days. the lack of alt correlated with lack of lung protection for 14 days post-m.tb challenge. to further i ... | 2012 | 22453678 |
| electrochemical monitoring of the metabolic activity of mycobacteria in culture. | mycobacterial metabolic activity is typically measured using time-consuming manual methods based on nutrient consumption, nucleic acid synthesis or reduction of tetrazolium salts. in this study, we propose much simpler electrochemical methods for continuous monitoring of the metabolic activity of mycobacteria in culture. chronoamperometry and chronopotentiometry were used to detect metabolic activity of both slow-growing and fast-growing mycobacteria using a potentiostat with 2d-electrochemical ... | 2012 | 22453520 |
| structure-based design of novel benzoxazinorifamycins with potent binding affinity to wild-type and rifampin-resistant mutant mycobacterium tuberculosis rna polymerases. | by utilization of three-dimensional structure information of rifamycins bound to rna polymerase (rnap) and the human pregnane x receptor (hpxr), representative examples (2b-d) of a novel subclass of benzoxazinorifamycins have been synthesized. relative to rifalazil (2a), these analogues generally display superior affinity toward wild-type and rif-resistant mutants of the mycobacterium tuberculosis rnap but lowered antitubercular activity in cell culture under both aerobic and anaerobic condition ... | 2012 | 22452568 |
| in silico discovery and virtual screening of multi-target inhibitors for proteins in mycobacterium tuberculosis. | mycobacterium tuberculosis (mtb) is the principal pathogen which causes tuberculosis (tb), a disease that remains as one of the most alarming health problems worldwide. an active area for the search of new anti-tb therapies is concerned with the use of computational approaches based on chemoinformatics and/or bioinformatics toward the discovery of new and potent anti-tb agents. these approaches consider only small series of structurally related compounds and the studies are generally realized fo ... | 2012 | 22452349 |
| nonprocessive [2 + 2]e- off-loading reductase domains from mycobacterial nonribosomal peptide synthetases. | in mycobacteria, polyketide synthases and nonribosomal peptide synthetases (nrpss) produce complex lipidic metabolites by using a thio-template mechanism of catalysis. in this study, we demonstrate that off-loading reductase (r) domain of mycobacterial nrpss performs two consecutive [2 + 2]e(-) reductions to release thioester-bound lipopeptides as corresponding alcohols, using a nonprocessive mechanism of catalysis. the first crystal structure of an r domain from mycobacterium tuberculosis nrps ... | 2012 | 22451903 |
| molecular characterization of multidrug-resistant mycobacterium tuberculosis isolated in nepal. | despite the fact that nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (mdr-tb) case management, the number of mdr-tb cases is continuing to rise in nepal. rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. to develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance in mycobacterium tuberculosis is ... | 2012 | 22450970 |
| meropenem-clavulanic acid shows activity against mycobacterium tuberculosis in vivo. | the carbapenems imipenem and meropenem in combination with clavulanic acid reduced the bacterial burden in mycobacterium tuberculosis-infected macrophages by 2 logs over 6 days. despite poor stability in solution and a short half-life in rodents, treatment of chronically infected mice revealed significant reductions of bacterial burden in the lungs and spleens. our results show that meropenem has activity in two in vivo systems, but stability and pharmacokinetics of long-term administration will ... | 2012 | 22450968 |
| discovery of selective menaquinone biosynthesis inhibitors against mycobacterium tuberculosis. | aurachin re (1) is a strong antibiotic that was recently found to possess 1,4-dihydroxy-2-naphthoate prenyltransferase (mena) and bacterial electron transport inhibitory activities. aurachin re is the only molecule in a series of aurachin natural products that has the chiral center in the alkyl side chain at c9'-position. to identify selective mena inhibitors against mycobacterium tuberculosis , a series of chiral molecules were designed based on the structures of previously identified mena inhi ... | 2012 | 22449052 |
| design, synthesis, and structure-activity correlations of novel dibenzo[b,d]furan, dibenzo[b,d]thiophene, and n-methylcarbazole clubbed 1,2,3-triazoles as potent inhibitors of mycobacterium tuberculosis. | a molecular hybridization approach is an emerging structural modification tool to design new molecules with improved pharmacophoric properties. in this study, 1,2,3-triazole-based mycobacterium tuberculosis inhibitors and synthetic and natural product-based tricyclic (carbazole, dibenzo[b,d]furan, and dibenzo[b,d]thiophene) antimycobacterial agents were integrated in one molecular platform to prepare various novel clubbed 1,2,3-triazole hybrids using click chemistry. structure-activity correlati ... | 2012 | 22449006 |
| understanding communication signals during mycobacterial latency through predicted genome-wide protein interactions and boolean modeling. | about 90% of the people infected with mycobacterium tuberculosis carry latent bacteria that are believed to get activated upon immune suppression. one of the fundamental challenges in the control of tuberculosis is therefore to understand molecular mechanisms involved in the onset of latency and/or reactivation. we have attempted to address this problem at the systems level by a combination of predicted functional protein:protein interactions, integration of functional interactions with large sc ... | 2012 | 22448278 |
| evaluation of tuberculosis diagnostics in children: 1. proposed clinical case definitions for classification of intrathoracic tuberculosis disease. consensus from an expert panel. | there is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. there is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of mycobacterium tuberculosis. a p ... | 2012 | 22448023 |
| the immunological footprint of mycobacterium tuberculosis t-cell epitope recognition. | aerosols containing mycobacterium tuberculosis (mtb) generated from the cough of patients with active pulmonary tuberculosis are the source of mtb infection. about 70% of individuals exposed to infected aerosols do not get infected, depending on the intensity and duration of mtb exposure. only 40% of the rest of the individuals (about 10% of those originally exposed) develop primary tuberculosis, whereas the remaining 60% contain the infection with generation of a robust immune response leading ... | 2012 | 22448020 |