Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| current advances in antitubercular drug discovery: potent prototypes and new targets. | tuberculosis (tb) is an infectious disease caused by bacterium of the mycobacterium genus, mainly by mycobacterium tuberculosis (mtb). the world health organization aims to substantially reduce the number of cases in the coming years; however, the increased number of multidrug-resistant (mdr) and extremely drug-resistant (xdr) forms of the bacterium and the lack of treatment for latent tuberculosis are challenges to be overcome. in this review, we have identified the most potent compounds descri ... | 2015 | 26282941 |
| interleukin 27r regulates cd4+ t cell phenotype and impacts protective immunity during mycobacterium tuberculosis infection. | cd4+ t cells mediate protection against mycobacterium tuberculosis (mtb); however, the phenotype of protective t cells is undefined, thereby confounding vaccination efforts. il-27 is highly expressed during human tuberculosis (tb), and absence of il-27r (il27ra) specifically on t cells results in increased protection. il-27r deficiency during chronic mtb infection does not impact antigen-specific cd4+ t cell number but maintains programmed death-1 (pd-1), cd69, and cd127 expression while reducin ... | 2015 | 26282876 |
| linked pyridinyl-thiadiazoles: design and synthesis as potential candidate for treatment of xdr and mdr tuberculosis. | multi-drug resistant (mdr) and extremely drug resistant (xdr) mycobacterium tuberculosis strains have turned tuberculosis (tb) as "on the verge of eradication" to "most life threatening" disease. furthermore, synergy with hiv and other immunosuppressive disease have strengthened its prevalence. this research reports small molecule anti-infectives which are specifically potent against several strains and isolates of tb. the hit compound 7f has also proved to be active against almost 25 clinical i ... | 2015 | 26280920 |
| the structure and interactions of periplasmic domains of crucial mmpl membrane proteins from mycobacterium tuberculosis. | mycobacterium tuberculosis mycobacterial membrane protein large (mmpl) proteins are important in substrate transport across the inner membrane. here, we show that mmpl proteins are classified into two phylogenetic clusters, where mmpl cluster ii contains three soluble domains (d1, d2, and d3) and has two full-length members, mmpl3 and mmpl11. significantly, mmpl3 is currently the most druggable m. tuberculosis target. we have solved the 2.4-å mmpl11-d2 crystal structure, revealing structural hom ... | 2015 | 26278184 |
| a side-by-side comparison of t cell reactivity to fifty-nine mycobacterium tuberculosis antigens in diverse populations from five continents. | we compared t cell recognition of 59 prevalently recognized mycobacterium tuberculosis (mtb) antigens in individuals latently infected with mtb (ltbi), and uninfected individuals with previous bcg vaccination, from nine locations and populations with different hla distribution, mtb exposure rates, and standards of tb care. this comparison revealed similar response magnitudes in diverse ltbi and bcg-vaccinated cohorts and significant correlation between responses in ltbis from the usa and other l ... | 2015 | 26277695 |
| clinical value of whole-genome sequencing of mycobacterium tuberculosis. | whole-genome sequencing (wgs) is now common as a result of new technologies that can rapidly sequence a complete bacterial genome for us$500 or less. many studies have addressed questions about tuberculosis with wgs, and knowing the sequence of the entire genome, rather than only a few fragments, has greatly increased the precision of molecular epidemiology and contact tracing. additionally, topics such as the mutation rate, drug resistance, the target of new drugs, and the phylogeny and evoluti ... | 2015 | 26277037 |
| rapid microbiological screening for tuberculosis in hiv-positive patients on the first day of acute hospital admission by systematic testing of urine samples using xpert mtb/rif: a prospective cohort in south africa. | autopsy studies of hiv/aids-related hospital deaths in sub-saharan africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (tb), which is found in 34-64 % of adult cadavers. we determined the overall prevalence and predictors of tb among consecutive unselected hiv-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with xpert mtb/rif (xpert). | 2015 | 26275908 |
| antifolate activity of plant polyphenols against mycobacterium tuberculosis. | with the view of exploring phytochemicals as mycobacterium tuberculosis (mtb) dihydrofolate reductase inhibitors, known plant polyphenols from various classes were subjected to detailed docking studies. from this in-silico screening, seven polyphenols were selected and tested against mtb h37 rv in whole cell assays. the phytochemicals exhibited potential activity ranging from 3 to 183 µm. these molecules were then tested against the pathogenic and human enzymes in a high-throughput microtitre as ... | 2015 | 26275674 |
| a case of manila type mycobacterium tuberculosis infection in japan. | a 76-year-old japanese woman contracted a mycobacterium tuberculosis (tb, manila type) infection in japan, despite never having traveled. however, her son was treated for tb in the philippines 3 years before he stayed at her house. spoligotyping allows us to identify the tb genotype and identify the route of infection. | 2015 | 26273455 |
| design of novel dispirooxindolopyrrolidine and dispirooxindolopyrrolothiazole derivatives as potential antitubercular agents. | with the aim to develop new potent antitubercular agents, a series of novel dispirooxindolopyrrolidines and dispirooxindolopyrrolothiazoles have been synthesized via a three-component 1,3-dipolar cycloaddition of (z)-3-arylidenebenzofuran-2-ones, substituted isatin derivatives and α-aminoacids. the stereochemistry of the spiroadducts has been confirmed by an x-ray diffraction analysis. all the target heterocycles were evaluated for in vitro antitubercular activity against mycobacterium tuberculo ... | 2015 | 26271585 |
| diversity of mycobacterium tuberculosis lineages in french polynesia. | french polynesia is an overseas territory located in the south pacific. the incidence of tuberculosis in french polynesia has been stable since 2000 with an average of 20 cases/y/100,000 inhabitants. molecular epidemiology of mycobacterium tuberculosis in french polynesia is unknown because m. tuberculosis isolates have not been routinely genotyped. | 2015 | 26271142 |
| diacyltransferase activity and chain length specificity of mycobacterium tuberculosis papa5 in the synthesis of alkyl β-diol lipids. | although they are classified as gram-positive bacteria, corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related gram-negative bacteria. like lipopolysaccharide in gram-negative bacteria, lipids in the outer membrane of corynebacterineae have been associated with the virulence of pathogenic species such as mycobacterium tuberculosis (mtb). for example, mtb strains that lack long, branched-chain alkyl esters know ... | 2015 | 26271001 |
| modulation of the activity of mycobacterium tuberculosis lipy by its pe domain. | mycobacterium tuberculosis harbors over 160 genes encoding pe/ppe proteins, several of which have roles in the pathogen's virulence. a number of pe/ppe proteins are secreted via type vii secretion systems known as the esx secretion systems. one pe protein, lipy, has a triglyceride lipase domain in addition to its pe domain. lipy can regulate intracellular triglyceride levels and is also exported to the cell wall by one of the esx family members, esx-5. upon export, lipy's pe domain is removed by ... | 2015 | 26270534 |
| in-vivo gene signatures of mycobacterium tuberculosis in c3heb/fej mice. | despite considerable progress in understanding the pathogenesis of mycobacterium tuberculosis (mtb), development of new therapeutics and vaccines against it has proven difficult. this is at least in part due to the use of less than optimal models of in-vivo mtb infection, which has precluded a study of the physiology of the pathogen in niches where it actually persists. c3heb/fej (kramnik) mice develop human-like lesions when experimentally infected with mtb and thus make available, a faithful a ... | 2015 | 26270051 |
| persistent infection by a mycobacterium tuberculosis strain that was theorized to have advantageous properties, as it was responsible for a massive outbreak. | the strains involved in tuberculosis outbreaks are considered highly virulent and transmissible. we analyzed the case of a patient in madrid, spain, who was persistently infected over an 8-year period by the same beijing mycobacterium tuberculosis strain. the strain was responsible for a severe outbreak on gran canaria island. the case provides us with a unique opportunity to challenge our assumptions about m. tuberculosis beijing strains. no clinical/radiological findings consistent with a viru ... | 2015 | 26269618 |
| the mycobacterial iron-dependent regulator ider induces ferritin (bfrb) by alleviating lsr2 repression. | emerging evidence indicates that precise regulation of iron (fe) metabolism and maintenance of fe homeostasis in mycobacterium tuberculosis (mtb) are essential for its survival and proliferation in the host. ider is a central transcriptional regulator of mtb genes involved in fe metabolism. while it is well understood how ider functions as a repressor, how it induces transcription of a subset of its targets is still unclear. we investigated the molecular mechanism of ider-mediated positive regul ... | 2015 | 26268801 |
| heme oxygenase-1 regulation of matrix metalloproteinase-1 expression underlies distinct disease profiles in tuberculosis. | pulmonary tuberculosis (tb) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (mmps). the interplay between these distinct pathological processes and the implications for tb diagnosis and disease staging are poorly understood. heme oxygenase-1 (ho-1) levels were previously shown to distinguish active from latent tb, as well as successfully treated mycobacterium tuberculosis infection. mmp-1 expression is also associated with active tb. in this study, w ... | 2015 | 26268658 |
| role of b cells in mucosal vaccine-induced protective cd8+ t cell immunity against pulmonary tuberculosis. | emerging evidence suggests a role of b cells in host defense against primary pulmonary tuberculosis (tb). however, the role of b cells in tb vaccine-induced protective t cell immunity still remains unknown. using a viral-vectored model tb vaccine and a number of experimental approaches, we have investigated the role of b cells in respiratory mucosal vaccine-induced t cell responses and protection against pulmonary tb. we found that respiratory mucosal vaccination activated ag-specific b cell res ... | 2015 | 26268652 |
| expanding the ubiquitin code through post-translational modification. | ubiquitylation is among the most prevalent post-translational modifications (ptms) and regulates numerous cellular functions. interestingly, ubiquitin (ub) can be itself modified by other ptms, including acetylation and phosphorylation. acetylation of ub on k6 and k48 represses the formation and elongation of ub chains. phosphorylation of ub happens on multiple sites, s57 and s65 being the most frequently modified in yeast and mammalian cells, respectively. in mammals, the pink1 kinase activates ... | 2015 | 26268526 |
| [the effect of mtb antigens on the nfat5 expression in monocytes from human peripheral blood]. | to study the effect of mycobacterium tuberculosis antigens early secretory antigen target 6/culture filtrate protein 10 (esat-6/cfp-10) on nuclear factor of activated t-cells 5 (nfat5) mrna in monocytes from human peripheral blood. | 2015 | 26268236 |
| oncocytic renal cell carcinoma with tubulopapillary growth having a fat component. | we report a rare case of oncocytic renal cell carcinoma (rcc) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. histology of the renal mass consisted of oncocytic cells forming solid, thin tubules and rare papillae. the tumor had abundant eosinophilic oncocytic cells containing occasional cytoplasmic mallory body-like hyaline globules and a tiny focus of clear cells with intervening mature fat. both the oncocytic cells and clear cells were immunoreactive for ... | 2015 | 26265689 |
| mycobacterium tuberculosis low molecular weight phosphatases (mptpa and mptpb): from biological insight to inhibitors. | mycobacterium tuberculosis (mtb), the main aetiological agent of tuberculosis (tb) in humans, is estimated to cause nearly two million deaths every year. despite their huge therapeutic value, existing antitubercular drugs have several shortcomings, such as for instance the insurgence of drug resistance, which is mostly triggered by lack of compliance during the lengthy treatment. novel and more effective drugs against mtb acting on new molecular targets are therefore in demand in order to reduce ... | 2015 | 26264920 |
| airway management of ruptured pulmonary artery "rasmussen" aneurysm and massive hemoptysis. | pulmonary tuberculosis is caused by mycobacterium tuberculosis and its manifestations may include parenchymal, airway, vascular, pleural, mediastinal and chest wall lesions. hemoptysis is a common complication of the disease. massive hemoptysis occurs in about 8% of cases; with associated mortality ranging from 5 to 25% massive hemoptysis secondary to pulmonary artery aneurysm rupture is a rare phenomenon presenting unique challenges in airway management and stabilization of oxygenation, ventila ... | 2015 | 26264527 |
| conserved hypothetical protein rv1977 in mycobacterium tuberculosis strains contains sequence polymorphisms and might be involved in ongoing immune evasion. | host immune pressure and associated parasite immune evasion are key features of host-pathogen co-evolution. a previous study showed that human t cell epitopes of mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that m. tuberculosis lacks antigenic variation and immune evasion. here, we selected 151 clinical mycobacterium tuberculosis isolates from china, amplified gene encoding rv1977 and compared the sequences. the results showed that rv1977, a conserved hypo ... | 2015 | 26261576 |
| two cases of erythema induratum of bazin--a rare cutaneous manifestation of tuberculosis. | tuberculosis remains a global disease burden, counting more than 9 million new cases per year. tuberculosis is caused by infection with mycobacterium tuberculosis-complex. though most commonly affecting the lungs, any organ can become a site of tuberculous infection. cutaneous tuberculosis is rare, representing 1-2% of all cases of tuberculosis. there are numerous different cutaneous manifestations of tuberculosis. we describe two cases of erythema induratum of bazin, a so-called tuberculid mani ... | 2015 | 26261059 |
| tuberculosis (hiv-negative people): improving adherence. | about one third of the world's population has immunological evidence of previous exposure to mycobacterium tuberculosis. in 2013, an estimated 9.0 million people developed tuberculosis (tb) and 1.5 million died from the disease. | 2015 | 26260866 |
| conventional and real-time pcr targeting 16s ribosomal rna for the detection of mycobacterium tuberculosis complex. | conventional diagnostic methods for tuberculosis (tb) have limited sensitivity and specificity or are time-consuming. | 2015 | 26260833 |
| contribution of xpert® mtb/rif to the diagnosis of pulmonary tuberculosis among tb-exposed children in the gambia. | greater banjul area, the gambia. | 2015 | 26260831 |
| false-negative bd mgit™ tbc identification test results in routine tuberculosis diagnosis: a new zealand perspective. | >we previously reported on a comparison of the accuprobe(®) gen-probe(®) mtbc assay (accuprobe) (biomérieux, marcy l'etoile, france) with the becton dickinson (bd) mgit™ tbc identification (tbc) test (bd, franklin lakes, nj, usa) in our laboratory. in the period following the shift from the accuprobe assay to the tbc test, we obtained six false-negative results. on sequencing the mpt64 gene, we found that these false-negative cases had mutations in the mpt64 gene due to deletion, insertion or su ... | 2015 | 26260827 |
| two distinct conformational states of mycobacterium tuberculosis virulent factor early secreted antigenic target 6 kda are behind the discrepancy around its biological functions. | early secreted antigenic target 6 kda (esat-6) and culture filtrate protein 10 kda (cfp-10) are complex proteins secreted by mycobacterium tuberculosis that play a major role in the pathogenesis of tuberculosis. however, studies focusing on the biological functions of esat-6 led to discordant results and the role of esat-6 remains controversial. in the present study, we aim to address a potential explanation for this discrepancy and to highlight the physiological impact of two conformational sta ... | 2015 | 26260636 |
| [determination of critical concentration of chemotherapy drugs for mycobacterium tuberculosis sensitivity evaluation using sensititre mycotb test system]. | determination of critical concentration for chemotherapy drugs, widely used for tuberculosis treatment, for use in mycobacterium tuberculosis drug sensitivity results evaluation by sensititre mycotb test-system. | 2015 | 26259272 |
| two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in mycobacterium tuberculosis. | the human pathogen mycobacterium tuberculosis (mtb) likely utilizes host fatty acids as a carbon source during infection. gluconeogenesis is essential for the conversion of fatty acids into biomass. a rate-limiting step in gluconeogenesis is the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate by a fructose bisphosphatase (fbpase). the mtb genome contains only one annotated fbpase gene, glpx. here we show that, unexpectedly, an mtb mutant lacking glpx grows on gluconeogenic carbon ... | 2015 | 26258286 |
| innate immune defenses in human tuberculosis: an overview of the interactions between mycobacterium tuberculosis and innate immune cells. | tuberculosis (tb) remains a serious global public health problem that results in up to 2 million deaths each year. tb is caused by the human pathogen, mycobacterium tuberculosis (mtb), which infects primarily innate immune cells patrolling the lung. innate immune cells serve as barometers of the immune response against mtb infection by determining the inflammatory milieu in the lungs and promoting the generation of adaptive immune responses. however, innate immune cells are also potential niches ... | 2015 | 26258152 |
| transcriptional profiling of mycobacterium tuberculosis replicating in the human type ii alveolar epithelial cell line, a549. | alveolar epithelial cells outnumber alveolar macrophages by ~500 fold and increasing evidence suggests mycobacterium tuberculosis may replicate dramatically in these cells during the initial weeks of infecting the lung [1,2]. here, we report in experimental detail the transcriptional profiling of mycobacterium tuberculosis replicating at 72 hr post-infection in the human type ii alveolar epithelial cell line, a549, as compared to mycobacterium tuberculosis growing logarithmically in laboratory b ... | 2015 | 26258047 |
| evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights. | the metabolic instability of an antitubercular small molecule cd117 was addressed through iterative alteration of a key sulfide substituent and interrogation of the effect on growth inhibition of cultured mycobacterium tuberculosis. this process was informed by studies of the intramycobacterial metabolism of cd117 and its inactive carboxylic acid derivative. isoxazole 4e and thiazole 4m demonstrated significant gains in mouse liver microsomal stability with slight losses in whole-cell activity. ... | 2015 | 26257441 |
| cavities create a potential back door in epoxide hydrolase rv1938 from mycobacterium tuberculosis-a molecular dynamics simulation study. | mycobacterium tuberculosis (mtb) is the causative organism of tuberculosis. extensively drug resistant strains and latency have posed formidable challenges in the treatment of tuberculosis. the current study addresses an alpha/beta hydrolase fold bearing enzyme, epoxide hydrolase rv1938 from mtb. epoxide hydrolases are involved in detoxification processes, catabolism and regulation of signaling molecules. using gromacs, a 100ns molecular dynamics (md) simulation was performed for rv1938. cavitie ... | 2015 | 26256802 |
| pyrosequencing for rapid detection of mycobacterium tuberculosis second-line drugs and ethambutol resistance. | the aim of this work was to study the diagnostic accuracy of pyrosequencing to detect resistance to fluoroquinolones, kanamycin, amikacin, capreomycin, and ethambutol (emb) in mycobacterium tuberculosis clinical strains. one hundred four clinical isolates previously characterized by bactec 460tb/mgit 960 were included. specific mutations were targeted in gyra, rrs, eis promoter, and embb. when there was a discordant result between bactec and pyrosequencing, genotype mtbdrsl (hain lifescience, ne ... | 2015 | 26256417 |
| assessment of cd27 expression as a tool for active and latent tuberculosis diagnosis. | there are still no reliable tests to distinguish active tuberculosis (tb) from latent tb infection (ltbi). assessment of cd27 modulation on cd4⁺ t-cells has been suggested as a tool to diagnose different tb stages. | 2015 | 26253021 |
| risk of disease after isoniazid preventive therapy for mycobacterium tuberculosis exposure in young hiv-uninfected children. | the risk of developing tuberculosis (tb) disease in hiv-uninfected children after isoniazid preventive therapy (ipt) for a positive quantiferon-tb gold in-tube test (qft-git) is unknown. the aim of this study was to evaluate risk of tb disease after ipt in young hiv-uninfected children with a positive qft-git result, or household tb contact. | 2015 | 26252568 |
| novel katg mutations causing isoniazid resistance in clinical m. tuberculosis isolates. | we report the discovery and confirmation of 23 novel mutations with previously undocumented role in isoniazid (inh) drug resistance, in catalase-peroxidase (katg) gene of mycobacterium tuberculosis (mtb) isolates. with these mutations, a synonymous mutation in fabg1 (g609a), and two canonical mutations, we were able to explain 98% of the phenotypic resistance observed in 366 clinical mtb isolates collected from four high tuberculosis (tb)-burden countries: india, moldova, philippines, and south ... | 2015 | 26251830 |
| one nanoprobe, two pathogens: gold nanoprobes multiplexing for point-of-care. | gold nanoparticles have been widely employed for biosensing purposes with remarkable efficacy for dna detection. amongst the proposed systems, colorimetric strategies based on the remarkable optical properties have provided for simple yet effective sequence discrimination with potential for molecular diagnostics at point of need. these systems may also been used for parallel detection of several targets to provide additional information on diagnostics of pathogens. | 2015 | 26250828 |
| biomarkers for risk of developing active tuberculosis in contacts of tb patients: a prospective cohort study. | identifying those mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (tb) using routine clinical and laboratory tests remains a huge challenge in tb control efforts. we conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active tb in contacts with latent m. tuberculosis infection.hiv-negative household contacts (n=296) of pulmonary tb patients underwent monitoring of clinical featu ... | 2015 | 26250497 |
| crystallographic studies of the extracytoplasmic function σ factor σ(j) from mycobacterium tuberculosis. | mycobacterium tuberculosis has multiple σ factors which enable the bacterium to reprogram its transcriptional machinery under diverse environmental conditions. σ(j), an extracytoplasmic function σ factor, is upregulated in late stationary phase cultures and during human macrophage infection. σ(j) governs the cellular response to hydrogen peroxide-mediated oxidative stress. σ(j) differs from other canonical σ factors owing to the presence of a snoal_2 domain at the c-terminus. σ(j) crystals belon ... | 2015 | 26249679 |
| the epidemiological characteristics of beijing lineage mycobacterium tuberculosis from a national referral center in china. | our study was to investigate the epidemiological characteristics of m.tuberculosis from a national tuberculosis referral center in china. all strains isolated from tb patients, were genotyped by the rd105 deletion, 8 and 51 snp loci and vntr. the high differentiation snps of modern beijing strains were analyzed for protein function and structure. 413 m. tuberculosis were included. of 379 beijing lineage m. tuberculosis, 'modern' and 'ancient' strains respectively represented 85.5% (324/379) and ... | 2015 | 26248739 |
| optimization and evaluation of 5-styryl-oxathiazol-2-one mycobacterium tuberculosis proteasome inhibitors as potential antitubercular agents. | this is the first report of 5-styryl-oxathiazol-2-ones as inhibitors of the mycobacterium tuberculosis (mtb) proteasome. as part of the study, the structure-activity relationship of oxathiazolones as mtb proteasome inhibitors has been investigated. furthermore, the prepared compounds displayed a good selectivity profile for mtb compared to the human proteasome. the 5-styryl-oxathiazol-2-one inhibitors identified showed little activity against replicating mtb, but were rapidly bactericidal agains ... | 2015 | 26246997 |
| lab-on-chip-based platform for fast molecular diagnosis of multidrug-resistant tuberculosis. | we evaluated the performance of the molecular lab-on-chip-based vereplex biosystem for detection of multidrug-resistant tuberculosis (mdr-tb), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and mtbdrplus assay for mycobacterium tuberculosis complex and rifampin and isoniazid resistance detection on clinical isolates and smear-positive specimens. the speed, user-friendly interface, and versatility make it suitable for routine laboratory use. | 2015 | 26246486 |
| ubiquitination as a mechanism to transport soluble mycobacterial and eukaryotic proteins to exosomes. | exosomes are extracellular vesicles of endocytic origin that function in intercellular communication. our previous studies indicate that exosomes released from mycobacterium tuberculosis-infected macrophages contain soluble mycobacterial proteins. however, it was unclear how these secreted proteins were targeted to exosomes. in this study, we determined that exosome production by the murine macrophage cell line raw264.7 requires the endosomal sorting complexes required for transport and that tra ... | 2015 | 26246139 |
| novel t-cell assays for the discrimination of active and latent tuberculosis infection: the diagnostic value of ppe family. | the diagnosis of active and latent tuberculosis remains a challenge. although a new approach based on detecting mycobacterium tuberculosis-specific t-cells has been introduced, it cannot distinguish between latent infection and active disease. the aim of this study was to evaluate the diagnostic potential of interleukin-2 (il-2) as biomarker after specific antigen stimulation with pe35 and ppe68 for the discrimination of active and latent tuberculosis infection (ltbi). | 2015 | 26245995 |
| crystal structures of mycobacterium tuberculosis glge and complexes with non-covalent inhibitors. | glge is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. in mycobacterium tuberculosis (m. tb), inactivation of glge (mtb glge) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (m1p), suggesting that glge is an intriguing target for inhibitor design. in this study, the crystal structures of the mtb glge in a binary complex with maltose and a ternary complex with maltose and a maltosyl ... | 2015 | 26245983 |
| andrographolide: a potent antituberculosis compound that targets aminoglycoside 2'-n-acetyltransferase in mycobacterium tuberculosis. | tuberculosis (tb) still remains a major challenging infectious disease. the increased rate of emergence of multi-drug resistant and extensively-drug resistant strains of the organism has further complicated the situation, resulting in an urgent need for new anti-tb drugs. antimycobacterial activity of andrographis paniculata was evaluated using a rapid lrp assay and the probable targets were identified by docking analysis. the methanolic extract of a. paniculata showed maximum antimycobacterial ... | 2015 | 26245695 |
| cell division inhibitors with efficacy equivalent to isoniazid in the acute murine mycobacterium tuberculosis infection model. | the increasing number of clinical strains resistant to one or more of the front-line tb drugs complicates the management of this disease. to develop next-generation benzimidazole-based ftsz inhibitors with improved efficacy, we employed iterative optimization strategies based on whole bacteria potency, bactericidal activity, plasma and metabolic stability and in vivo efficacy studies. | 2015 | 26245639 |
| molecular typing and drug sensitivity testing of mycobacterium tuberculosis isolated by a community-based survey in ethiopia. | the identification of circulating tb strains in the community and drug sensitivity patterns is essential for the tuberculosis control program. this study was undertaken to identify m. tuberculosis strains circulating in selected communities in ethiopia as well as to evaluate the drug sensitivity pattern of these strains. | 2015 | 26245282 |
| differential proteomics approach to identify putative protective antigens of mycobacterium tuberculosis presented during early stages of macrophage infection and their evaluation as dna vaccines. | unsatisfactory performance of the existing bcg vaccines, especially against the adult pulmonary disease, has urged the need for an effective vaccine against tuberculosis (tb). in this study, we employed differential proteomics to obtain a list of antigens as potential vaccine candidates. bacterial epitopes being presented at early stages on mhc class i and class ii molecules of macrophages infected with mycobacterium tuberculosis (m. tb) were identified using itraq labelling and reverse phase lc ... | 2015 | 26245027 |
| 3d-qsar selectivity analysis of 1-adamantyl-3-heteroaryl urea analogs as potent inhibitors of mycobacterium tuberculosis. | a 3d-qsar selectivity analysis of 53 adamantyl heteroaryl urea derivatives active against m. tuberculosis is reported. these analogs inhibit mycobacterial membrane protein large 3 (mmpl3), a proposed transporter for cell wall mycolic acids. however, these analogs also exhibit affinity towards human soluble epoxide hydrolase (seh) enzyme, making them pharmacologically undesirable. thus, comfa and comsia selective studies viz ligand and receptor-based alignment has been described to evaluate key p ... | 2015 | 26234390 |
| discovery of new [formula: see text] proteasome inhibitors using a knowledge-based computational screening approach. | mycobacterium tuberculosis bacteria cause deadly infections in patients [corrected]. the rise of multidrug resistance associated with tuberculosis further makes the situation worse in treating the disease. m. tuberculosis proteasome is necessary for the pathogenesis of the bacterium validated as an anti-tubercular target, thus making it an attractive enzyme for designing mtb inhibitors. in this study, a computational screening approach was applied to identify new proteasome inhibitor candidates ... | 2015 | 26232029 |
| the serine/threonine kinase pknb of mycobacterium tuberculosis phosphorylates pbpa, a penicillin-binding protein required for cell division. | the authors would like to retract the article as the published versions of figs. 3b, 6a, b, d, 7a, b(lower panel) were modified prior to publication. the authors would like to apologise to thereaders, reviewers and editors of microbiology for this error. | 2015 | 26231854 |
| genetic diversity and molecular epidemiology of multidrug-resistant mycobacterium tuberculosis in minas gerais state, brazil. | we aimed to characterize the genetic diversity of drug-resistant mycobacterium tuberculosis (mtb) clinical isolates and investigate the molecular epidemiology of multidrug-resistant (mdr) tuberculosis from minas gerais state, brazil. | 2015 | 26231661 |
| fast and efficient detection of tuberculosis antigens using liposome encapsulated secretory proteins of mycobacterium tuberculosis. | a rapid and efficient diagnostic test was developed for the detection of mycobacterium tuberculosis antigens in serum samples of active tuberculosis (tb) and extrapulmonary tb patients via a liposomal agglutination-based method. | 2015 | 26231299 |
| potion: an end-to-end pipeline for positive darwinian selection detection in genome-scale data through phylogenetic comparison of protein-coding genes. | detection of genes evolving under positive darwinian evolution in genome-scale data is nowadays a prevailing strategy in comparative genomics studies to identify genes potentially involved in adaptation processes. despite the large number of studies aiming to detect and contextualize such gene sets, there is virtually no software available to perform this task in a general, automatic, large-scale and reliable manner. this certainly occurs due to the computational challenges involved in this task ... | 2015 | 26231214 |
| design, development, drug-likeness, and molecular docking studies of novel piperidin-4-imine derivatives as antitubercular agents. | tuberculosis remains one of the major grievous diseases worldwide. the emergence of resistance to antituberculosis drugs emphasize the necessity to discover new therapeutic agents for preferential tuberculosis therapy. in this study, various novel 1-(1h-benzimidazol-2-ylmethyl) piperidin-4-imine derivatives were developed and checked for favorable pharmacokinetic parameters based on drug-likeness explained by lipinski's rule of five. all 20 of the novel chemical entities were found to possess a ... | 2015 | 26229439 |
| regulation of ergothioneine biosynthesis and its effect on mycobacterium tuberculosis growth and infectivity. | ergothioneine (egt) is synthesized in mycobacteria, but limited knowledge exists regarding its synthesis, physiological role, and regulation. we have identified rv3701c from mycobacterium tuberculosis to encode for egtd, a required histidine methyltransferase that catalyzes first biosynthesis step in egt biosynthesis. egtd was found to be phosphorylated by the serine/threonine protein kinase pknd. pknd phosphorylates egtd both in vitro and in a cell-based system on thr(213). the phosphomimetic ( ... | 2015 | 26229105 |
| rd-1 encoded espj protein gets phosphorylated prior to affect the growth and intracellular survival of mycobacteria. | mycobacterium tuberculosis (mtb) synchronizes a number of processes and controls a series of events to subvert host defense mechanisms for the sake of residing inside macrophages. besides these, mtb also possesses a wide range of signal enzyme systems, including eleven serine threonine protein kinases (stpks). the present study describes stpk modulated modification in one of the hypothetical proteins of the rd1 region; espj (esx-1 secretion associated protein), which is predicted to be involved ... | 2015 | 26228622 |
| the role of clinical symptoms in the diagnosis of intrathoracic tuberculosis in young children. | childhood tuberculosis (tb) is usually mycobacterium tuberculosis (mtb) culture negative. furthermore, clinical presentation may be altered by active case finding, isoniazid prophylaxis and early treatment. we aimed to establish the value of presenting symptoms for intrathoracic tb case diagnosis among young children. | 2015 | 26226446 |
| ubiquilin 1 promotes ifn-γ-induced xenophagy of mycobacterium tuberculosis. | the success of mycobacterium tuberculosis (mtb) as a pathogen rests upon its ability to grow intracellularly in macrophages. interferon-gamma (ifn-γ) is critical in host defense against mtb and stimulates macrophage clearance of mtb through an autophagy pathway. here we show that the host protein ubiquilin 1 (ubqln1) promotes ifn-γ-mediated autophagic clearance of mtb. ubiquilin family members have previously been shown to recognize proteins that aggregate in neurodegenerative disorders. we find ... | 2015 | 26225865 |
| systematic analysis of hollow fiber model of tuberculosis experiments. | the in vitro hollow fiber system model of tuberculosis (hfs-tb), in tandem with monte carlo experiments, was introduced more than a decade ago. since then, it has been used to perform a large number of tuberculosis pharmacokinetics/pharmacodynamics (pk/pd) studies that have not been subjected to systematic analysis. | 2015 | 26224767 |
| predictors for mtb culture-positivity among hiv-infected smear-negative presumptive tuberculosis patients in uganda: application of new tuberculosis diagnostic technology. | the existing world health organization diagnostic algorithms for smear-negative tb perform poorly in hiv-infected individuals. new tb diagnostics such as urine tb lipoarabinomannan (lam) could improve the accuracy and reduce delays in tb diagnosis in hiv-infected smear-negative presumptive tb. we sought to determine predictors for mtb culture-positivity among these patients. | 2015 | 26222142 |
| evaluation of four colourimetric susceptibility tests for the rapid detection of multidrug-resistant mycobacterium tuberculosis isolates. | the purpose of this study is to evaluate four rapid colourimetric methods, including the resazurin microtitre assay (rema), malachite green decolourisation assay (mgda), microplate nitrate reductase assay (mnra) and crystal violet decolourisation assay (cvda), for the rapid detection of multidrug-resistant (mdr) tuberculosis. fifty mycobacterium tuberculosis isolates were used in this study. eighteen isolates were mdr, two isolates were only resistant to isoniazid (inh) and the remaining isolate ... | 2015 | 26222021 |
| systemic lupus erythematosus accompanying with renal tuberculosis: a case report. | a 26-year-old woman, with a six-year history of well-controlled systemic lupus erythematosus (sle), complained of urinary frequency and urgency. after failure of commonly-used antibiotic therapy, mycobacterium tuberculosis was cultured from her urine and renal tuberculosis (tb) was diagnosed. however, she underwent right nephrectomy after the combination therapies of prednisone for sle and anti-tuberculosis treatment for renal tb failed. to our knowledge, sle accompanying renal tb is rare, and s ... | 2015 | 26221395 |
| mannose-capped lipoarabinomannan from mycobacterium tuberculosis induces il-37 production via upregulating erk1/2 and p38 in human type ii alveolar epithelial cells. | the major surface lipoglycan of mycobacterium tuberculosis (m. tb), mannose-capped lipoarabinomannan (manlam), is an immunosuppressive epitope of m. tb. interleukin (il)-37, is a newly identified anti-inflammatory cytokine, which reduces systemic and local inflammation. however, the correlation between manlam and il-37 remains unknown. therefore, in this study, we investigate the possible role and relative molecular mechanism of manlam in il-37 production of human type ii alveolar epithelial cel ... | 2015 | 26221267 |
| phylogenetic assignment of mycobacterium tuberculosis beijing clinical isolates in japan by maximum a posteriori estimation. | intra-species phylogeny of mycobacterium tuberculosis has been regarded as a clue to estimate its potential risk to develop drug-resistance and various epidemiological tendencies. genotypic characterization of variable number of tandem repeats (vntr), a standard tool to ascertain transmission routes, has been improving as a public health effort, but determining phylogenetic information from those efforts alone is difficult. we present a platform based on maximum a posteriori (map) estimation to ... | 2015 | 26220897 |
| newer diagnostic tests for pulmonary tuberculosis in children. | it has been well recognized that the diagnosis of pulmonary tuberculosis in children is often compromised by non-specific symptoms, paucibacillary nature of the disease, and the difficulty in collecting the specimen. consequently, most tuberculosis cases in children are not confirmed, due to which the estimation of the global burden of tuberculosis in children may be inaccurate. there has also been a common misperception that diagnosis of tuberculosis and collecting respiratory specimen in child ... | 2015 | 26220244 |
| host-directed therapies for tackling multi-drug resistant tuberculosis: learning from the pasteur-bechamp debates. | tuberculosis remains a global emergency causing an estimated 1.5 million deaths annually. for several decades the major focus of tuberculosis treatment has been on antibiotic development targeting mycobacterium tuberculosis. the lengthy tuberculosis treatment duration and poor treatment outcomes associated with multi-drug resistant tuberculosis (mdr-tb) are of major concern. the sparse new tuberculosis drug pipeline and widespread emergence of mdr-tb signal an urgent need for more innovative int ... | 2015 | 26219693 |
| differential levels of alpha-2-macroglobulin, haptoglobin and sero-transferrin as adjunct markers for tb diagnosis and disease progression in the malnourished tribal population of melghat, india. | lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (tb). point-of-care diagnostic tests for tb in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. the aim of the study was to identify potential biomarkers specific for tb infection and progression to overt disease in the malnourished population of melghat. a prospective cohort study was conducted in the year 2 ... | 2015 | 26241963 |
| disseminated tuberculosis in an hiv-infected child: rifampicin resistance detected by genexpert in a lymph node aspirate but not in cerebrospinal fluid. | a 9-year-old hiv-infected child previously treated with inadequate doses of antitubercular drugs based on weight was admitted 5 months after initial tuberculosis (tb) diagnosis with acute hemiplegia and inguinal lymphadenopathies in a rural hospital in tanzania. he was diagnosed with tb meningitis and lymphadenitis using xpert mycobacterium tuberculosis/rifampicin (mtb/rif) assay. rifampicin resistance was detected in the lymph node aspirate but not in the cerebrospinal fluid. his tb therapy was ... | 2015 | 26240094 |
| incubation time of mycobacterium tuberculosis complex sputum cultures in bactec mgit 960: 4weeks of negative culture is enough for physicians to consider alternative diagnoses. | we retrospectively analyzed time to detection of 3747 positive mgit sputum cultures at a laboratory in a country with heavy burden of tuberculosis. ninety-nine percent of diagnostic cultures turned positive within 28days, suggesting that physicians may consider alternative diagnoses if sputum cultures remain negative after 4weeks of incubation. | 2015 | 26239846 |
| [intestinal tuberculosis--a rare differential diagnosis of crohn's disease in an ethnic danish woman]. | we report a case of intestinal tuberculosis in a 42-year-old danish woman with stomach pain, weight loss and diarrhoea for months suspective of crohn's disease. she underwent hysterectomy where white, small nodules were found on the small intestine. biopsies showed non-necrotizing granulomatous inflammation. gastroscopy and colonoscopy were normal. capsule endoscopy revealed small intestine ulcers and a stenosis. a ct scan of the abdomen confirmed stenosis and inflammation of terminal ileum. qua ... | 2015 | 26239740 |
| proteomic analysis of ofloxacin-mono resistant mycobacterium tuberculosis isolates. | drug resistance particularly, multi drug resistance tuberculosis (mdr-tb) has emerged as a major problem in the chemotherapy of tuberculosis. ofloxacin (ofx) has been used as second-line drug against mdr-tb. the principal target of the ofx is dna gyrase encoded by gyra and gyrb genes. many explanations have been proposed for drug resistance to ofx but still some mechanisms are unknown. as proteins manifest most of the biological processes, these are attractive targets for developing drugs and di ... | 2015 | 26238929 |
| host and microbial predictors of childhood extrathoracic tuberculosis and tuberculosis meningitis. | childhood tuberculosis (tb) is a major infectious disease causing morbidity and mortality in children and yet has been largely ignored until recently. this study is the first study to characterize childhood tb in china incorporating both mycobacterium tuberculosis genetic characteristics and patient data. | 2015 | 26237743 |
| the tuberculosis necrotizing toxin kills macrophages by hydrolyzing nad. | mycobacterium tuberculosis (mtb) induces necrosis of infected cells to evade immune responses. recently, we found that mtb uses the protein cpnt to kill human macrophages by secreting its c-terminal domain, named tuberculosis necrotizing toxin (tnt), which induces necrosis by an unknown mechanism. here we show that tnt gains access to the cytosol of mtb-infected macrophages, where it hydrolyzes the essential coenzyme nad(+). expression or injection of a noncatalytic tnt mutant showed no cytotoxi ... | 2015 | 26237511 |
| co-infection of long-standing extensively drug-resistant mycobacterium tuberculosis (xdr-tb) and non-tuberculosis mycobacteria: a case report. | we report a 69-years-old iranian hiv negative male patient, with long-standing pulmonary tuberculosis (eleven years) co-infected with non-tuberculosis mycobacteria. despite of initiation of first line anti-tuberculosis therapy after diagnosis the patient poorly respond because of low compliance with anti-tb treatment. after several incomplete treatments the smear was still positive and thus drug susceptibility tests were performed on isolated organism which revealed that the organisms was resist ... | 2015 | 26236585 |
| flux balance analysis with objective function defined by proteomics data-metabolism of mycobacterium tuberculosis exposed to mefloquine. | we present a study of the metabolism of the mycobacterium tuberculosis after exposure to antibiotics using proteomics data and flux balance analysis (fba). the use of fba to study prokaryotic organisms is well-established and allows insights into the metabolic pathways chosen by the organisms under different environmental conditions. to apply fba a specific objective function must be selected that represents the metabolic goal of the organism. fba estimates the metabolism of the cell by linear p ... | 2015 | 26218987 |
| phenylbutyrate induces ll-37-dependent autophagy and intracellular killing of mycobacterium tuberculosis in human macrophages. | ll-37 is a human antimicrobial peptide (amp) of the cathelicidin family with multiple activities including a mediator of vitamin d-induced autophagy in human macrophages, resulting in intracellular killing of mycobacterium tuberculosis (mtb). in a previous trial in healthy volunteers, we have shown that ll-37 expression and subsequent mtb-killing can be further enhanced by 4-phenylbutyrate (pba), also an inducer of ll-37 expression. here, we explore a potential mechanism(s) behind pba and ll-37- ... | 2015 | 26218841 |
| the atpase activity of the mycobacterial plasma membrane is inhibited by the ll37-analogous peptide llap. | the emergence of multidrug-resistant mycobacterium tuberculosis strains has led to the development of new antituberculous agents. in this context, antimicrobial targeting proteins to the cell membrane are interesting due to the avoidance of the plasma membrane permeation. through this study, the antimicrobial activity, cellular toxicity, as well as the effect on the mycobacterial cell membrane atpase activity of a cathelicidin-analogous peptide were assessed. by using bioinformatics analyses, a ... | 2015 | 26218806 |
| coexistence of spinal intramedullary tuberculoma and multiple intracranial tuberculomas. | spinal intramedullary tuberculoma remains a very rare entity of central nervous system tuberculosis. this is the same with the coexistence of spinal intramedullary and intracranial tuberculomas that remains extremely rare with less than 20 cases reported at present. authors describe this uncommon case by analyzing a 65-year-old female patient who had past history of kidney transplantation due to stage 5 chronic kidney disease and pulmonary tuberculosis on medication. the patient experiences prog ... | 2015 | 26217392 |
| grisel's syndrome induced by mycobacterium tuberculosis. | grisel's syndrome is a non-traumatic subluxation of the atlantoaxial joints, which is caused by an inflammatory process in the upper neck. it is rare to find literary reports of grisel's syndrome with an evident pathogen in a lesion. for the first time in korea, we report a 36-year-old female with grisel's syndrome having an atlantoaxial subluxation, which was caused by a retropharyngeal abscess secondary to pulmonary mycobacterium tuberculosis. the patient was treated with an anti-tuberculosis ... | 2015 | 26217388 |
| acetate dissimilation and assimilation in mycobacterium tuberculosis depend on carbon availability. | mycobacterium tuberculosis persists inside granulomas in the human lung. analysis of the metabolic composition of granulomas from guinea pigs revealed that one of the organic acids accumulating in the course of infection is acetate (b. s. somashekar, a. g. amin, c. d. rithner, j. troudt, r. basaraba, a. izzo, d. c. crick, and d. chatterjee, j proteome res 10:4186-4195, 2011, doi:http://dx.doi.org/10.1021/pr2003352), which might result either from metabolism of the pathogen or might be provided b ... | 2015 | 26216844 |
| functional evaluation of residues in the herbicide-binding site of mycobacterium tuberculosis acetohydroxyacid synthase by site-directed mutagenesis. | mycobacterium tuberculosis acetohydroxyacid synthase (m. tuberculosis ahas) has been proposed to bean essential target for novel herbicide- and chemical-based antibacterial agents. therefore, here we investigated the roles of multiple conserved herbicide-binding site residues (r318, a146, q148, m512, and v513) in m. tuberculosis ahas through site-directed mutagenesis by characterizing the kinetic parameters and herbicide sensitivities of various point mutants. interestingly, all mutant enzymes s ... | 2015 | 26215340 |
| analysis of is6110 insertion sites provide a glimpse into genome evolution of mycobacterium tuberculosis. | insertion sequence (is) 6110 is found at multiple sites in the mycobacterium tuberculosis genome and displays a high degree of polymorphism with respect to copy number and insertion sites. therefore, is6110 is considered to be a useful molecular marker for diagnosis and strain typing of m. tuberculosis. generally is6110 elements are identified using experimental methods, useful for analysis of a limited number of isolates. since short read genome sequences generated using next-generation sequenc ... | 2015 | 26215170 |
| virtual screening for udp-galactopyranose mutase ligands identifies a new class of antimycobacterial agents. | galactofuranose (galf) is present in glycans critical for the virulence and viability of several pathogenic microbes, including mycobacterium tuberculosis, yet the monosaccharide is absent from mammalian glycans. uridine 5'-diphosphate-galactopyranose mutase (ugm) catalyzes the formation of udp-galf, which is required to produce galf-containing glycoconjugates. inhibitors of ugm have therefore been sought, both as antimicrobial leads and as tools to delineate the roles of galf in cells. obtainin ... | 2015 | 26214585 |
| comparative proteomics of activated thp-1 cells infected with mycobacterium tuberculosis identifies putative clearance biomarkers for tuberculosis treatment. | biomarkers for determining clearance of mycobacterium tuberculosis (mtb) infection during anti-tuberculosis therapy or following exposure could facilitate enhanced monitoring and treatment. we screened for biomarkers indicating clearance of mtb infection in vitro. a comparative proteomic analysis was performed using gelc msi/ms. intracellular and secreted proteomes from activated thp-1 cells infected with the mtb h37rv strain (moi = 1) and treated with isoniazid and rifampicin for 1 day (infecti ... | 2015 | 26214306 |
| n-cinnamoyltetraketide derivatives from the leaves of toussaintia orientalis. | seven n-cinnamoyltetraketides (1-7), including the new z-toussaintine e (2), toussaintine f (6), and toussaintine g (7), were isolated from the methanol extract of the leaves of toussaintia orientalis using column chromatography and hplc. the configurations of e-toussaintine e (1) and toussaintines a (3) and d (5) are revised based on single-crystal x-ray diffraction data from racemic crystals. both the crude methanol extract and the isolated constituents exhibit antimycobacterial activities (mi ... | 2015 | 26214247 |
| novel antitumor strategy utilizing a plasmid expressing a mycobacterium tuberculosis antigen as a "danger signal" to block immune escape of tumor cells. | immune escape of tumor cells is one of the main obstacles hindering the effectiveness of cancer immunotherapy. we developed a novel strategy to block immune escape by transfecting tumor cells in vivo with genes of pathogenic antigens from mycobacterium tuberculosis (tb). this induces presentation of the tb antigen on tumor cell surfaces, which can be recognized by antigen presenting cells (apcs) as a "danger signal" to stimulate antitumor immune response. this strategy is also expected to amplif ... | 2015 | 26213962 |
| callyaerins from the marine sponge callyspongia aerizusa: cyclic peptides with antitubercular activity. | chemical investigation of the indonesian sponge callyspongia aerizusa afforded five new cyclic peptides, callyaerins i-m (1-5), along with the known callyaerins a-g (6-12). the structures of the new compounds were unambiguously elucidated on the basis of one- and two-dimensional nmr spectroscopy and mass spectrometry. in addition, the structures of callyaerins d (9), f (11), and g (12), previously available in only small amounts, have been reinvestigated and revised. all compounds were tested in ... | 2015 | 26213786 |
| factors of suppression of immune response in patients with pulmonary tuberculosis and eosinophilia. | we studied possible mechanisms of immunosuppression mediated by regulatory t cells that promotes suppression of antigen-specific immune response to mycobacterium tuberculosis in patients with pulmonary tuberculosis and eosinophilia. it was shown that the number of cd4(+)cd25(+)foxp3(+) regulatory t cells with immunosuppressive activity (treg) increased in the peripheral blood of patients with disseminated destructive forms of pulmonary tuberculosis with multiple resistance of the causative agent ... | 2015 | 26212806 |
| contribution of mincle-syk signaling to activation of primary human apcs by mycobacterial cord factor and the novel adjuvant tdb. | trehalose-6,6-dimycolate (tdm), the mycobacterial cord factor, is an abundant cell wall glycolipid and major virulence factor of mycobacterium tuberculosis. its synthetic analog trehalose-6,6-dibehenate (tdb) is a new adjuvant currently in phase i clinical trials. in rodents, the c-type lectin receptors mincle and mcl bind tdb/tdm and activate macrophages and dendritic cells (dc) through the syk-card9 pathway. however, it is unknown whether these glycolipids activate human innate immune cells th ... | 2015 | 26202982 |
| proteomic analysis of extracellular vesicles derived from mycobacterium tuberculosis. | the release of extracellular vesicles, also known as outer membrane vesicles, membrane vesicles, exosomes, and microvesicles, is an evolutionarily conserved phenomenon from bacteria to eukaryotes. it has been reported that mycobacterium tuberculosis releases extracellular vesicles harboring immunologically active molecules, and these extracellular vesicles have been suggested to be applicable in vaccine development and biomarker discovery. however, the comprehensive proteomic analysis has not be ... | 2015 | 26201501 |
| the role of high mobility group box 1 protein (hmgb1) in the immunopathology of experimental pulmonary tuberculosis. | the high mobility group box 1 (hmgb1) is the prototype of alarmin protein released by stressed or dying cells. the redox state of this protein confers different functions in the regulation of inflammation and immune response. | 2015 | 26201072 |
| conformational dynamics of response regulator regx3 from mycobacterium tuberculosis. | two-component signal transduction systems (tcs) are vital for adaptive responses to various environmental stresses in bacteria, fungi and even plants. a tcs typically comprises of a sensor histidine kinase (sk) with its cognate response regulator (rr), which often has two domains-n terminal receiver domain (rd) and c terminal effector domain (ed). the histidine kinase phosphorylates the rd to activate the ed by promoting dimerization. however, despite significant progress on structural studies, ... | 2015 | 26201027 |
| lipoarabinomannan-specific tnf-α and ifn-γ as markers of protective immunity against tuberculosis: a cohort study in an endemic setting. | lipoarabinomannan (lam) is a virulent factor used for entry and survival of mycobacterium tuberculosis (mtb) in macrophages. although the role of lam for the diagnosis of tuberculosis (tb) has been extensively investigated, its cytokine response during natural mtb infection in humans is largely unknown. in this study, lam-specific ifn-γ, tnf-α, and il-10 levels following whole blood assay were measured in untreated pulmonary tb patients, their contacts and community controls at baseline. in trea ... | 2015 | 26200933 |
| synthesis and anti-tubercular activity of 2-nitroimidazooxazines with modification at the c-7 position as pa-824 analogs. | tuberculosis (tb) is a major global health problem, and new drug targets and scaffolds need to be identified to combat the emergence of drug resistant tb. the nitroimidazooxazine pa-824 represents a new class of bio-reductive drug to treat tb. in this study we report a 2-nitroimidazooxazine derivative with modification at the c-7 position that exhibited better activity than pa-824 against mycobacterium tuberculosis (mtb) h37rv strain in vitro. from 7a as a key intermediate, we functionalized wit ... | 2015 | 26199118 |