Publications

the use of zymosan a and bacteria anchored to tumor cells for effective cancer immunotherapy: b16-f10 murine melanoma model.	the idea of using killed microorganisms or their parts for a stimulation of immunity in the cancer immunotherapy is very old, but the question of interactions and binding of these preparations to tumor cells has not been addressed so far. the attachment of zymosan a and both gram-positive and gram-negative bacteria to tumor cells was tested in in vivo experiments. this binding was accomplished by charge interactions, anchoring based on hydrophobic chains and covalent bonds and proved to be cruci ...	2016	27505858
intracranial tuberculoma presenting as atypical eclampsia: a case report.	occurrence of eclampsia before 20 weeks of pregnancy and after 48 hours of delivery in the absence of typical signs of hypertension and or proteinuria is termed as atypical eclampsia. atypical or non-classic eclampsia will have some symptoms of eclampsia but without the usual proteinuria or hypertension. all patients with atypical onset should undergo neurological evaluation to rule out neurologic causes of seizures. cerebral tuberculosis is a rare and serious form of disease secondary to haemat ...	2016	27504359
discovery of novel oral protein synthesis inhibitors of mycobacterium tuberculosis that target leucyl-trna synthetase.	the recent development and spread of extensively drug-resistant and totally drug-resistant resistant (tdr) strains of mycobacterium tuberculosis highlight the need for new antitubercular drugs. protein synthesis inhibitors have played an important role in the treatment of tuberculosis (tb) starting with the inclusion of streptomycin in the first combination therapies. although parenteral aminoglycosides are a key component of therapy for multidrug-resistant tb, the oxazolidinone linezolid is the ...	2016	27503647
helminth-tuberculosis co-infection: an immunologic perspective.	over 2 billion people worldwide are infected with helminths (worms). similarly, infection with mycobacterium tuberculosis (mtb) occurs in over a third of the world's population, often with a great degree of geographical overlap with helminth infection. interestingly, the responses induced by the extracellular helminths and those induced by the intracellular mtb are often mutually antagonistic and, as a consequence, can result in impaired (or cross-regulated) host responses to either of the infec ...	2016	27501916
understanding the pathophysiology of the human tb lung granuloma using in vitro granuloma models.	tuberculosis remains a major human health threat that infects one in three individuals worldwide. infection with mycobacterium tuberculosis is a standoff between host and bacteria in the formation of a granuloma. this review will introduce a variety of bacterial and host factors that impact individual granuloma fates. the authors describe advances in the development of in vitro granuloma models, current evidence surrounding infection and granuloma development, and the applicability of existing i ...	2016	27501829
inhibition of mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues.	the mycobacterium tuberculosis dihydrodipicolinate synthase (mtb-dapa) is an essential gene. mtb-dapa catalyzes the aldol condensation between pyruvate and l-aspartate-beta-semialdehyde (asa) to yield dihydrodipicolinate. in this work we tested the inhibitory effects of structural analogues of pyruvate on recombinant mtb-dapa (mtb-rdapa) using a coupled assay with recombinant dihydrodipicolinate reductase (mtb-rdapb). alpha-ketopimelic acid (α-kpa) showed maximum inhibition of 88% and ic50 of 21 ...	2016	27501775
the mechanism for type i interferon induction by mycobacterium tuberculosis is bacterial strain-dependent.	type i interferons (including ifnαβ) are innate cytokines that may contribute to pathogenesis during mycobacterium tuberculosis (mtb) infection. to induce ifnβ, mtb must gain access to the host cytosol and trigger stimulator of interferon genes (sting) signaling. a recently proposed model suggests that mtb triggers sting signaling through bacterial dna binding cyclic gmp-amp synthase (cgas) in the cytosol. the aim of this study was to test the generalizability of this model using phylogeneticall ...	2016	27500737
tuberculous pleural effusion.	although it is curable, tuberculosis remains one of the most frequent causes of pleural effusions on a global scale, especially in developing countries. tuberculous pleural effusion (tpe) is one of the most common forms of extrapulmonary tuberculosis. tpe usually presents as an acute illness with fever, cough and pleuritic chest pain. the pleural fluid is an exudate that usually has predominantly lymphocytes. the gold standard for the diagnosis of tpe remains the detection of mycobacterium tuber ...	2016	27499981
designing and construction of a dna vaccine encoding tb10.4 gene of mycobacterium tuberculosis.	tuberculosis (tb) remains as a major cause of death. construction of a new vaccine against tuberculosis is an effective way to control it. several vaccines against this disease have been developed. the aim of the present study was to cloning of tb10.4 gene in pcdna3.1(+) plasmid and evaluation of its expression in eukaryotic cells.	2016	27499771
identification of mycobacterium tuberculosis in the cerebrospinal fluid of patients with meningitis using nested pcr.	tuberculous meningitis (tbm) is the most severe form of tuberculosis. it is caused by mycobacterium tuberculosis (m. tuberculosis; mt) and it is very difficult to diagnose. the symptoms are similar to other infectious neurological diseases, such as neurocysticercosis, neuroborreliosis, or herpes viral infection. the aim of this study was to identify tuberculosis (tb) in cases of meningitis with clinical and laboratory evidence suggestive of tbm, and to confirm our findings with molecular tests f ...	2016	27499078
mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.	although pulmonary epithelial cells are integral to innate and adaptive immune responses during mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. changes in gene expression induced in pulmonary epithelial cells infected with m. tuberculosis f15/lam4/kzn, f11, f28, beijing and unique genotypes were investigated by rna sequencing (rna-seq). the illumina hiseq 2000 platform generated 50 bp reads that were mapped to the human genome (hg19) usi ...	2016	27497873
comparative analysis of new peptide conjugates of antitubercular drug candidates-model membrane and in vitro studies.	novel peptide conjugates of two antitubercular drug candidates were synthesised and characterised using new tuftsin peptide derivative (ot14) as carrier moiety. as antitubercular drug candidates two pyridopyrimidine derivatives, tb803 (2-allylamino-4-oxopyrido[1,2-a]pyrimidine-3-carbaldehyde) and tb820 (4-oxo-2-(pyrrolidin-1-yl)-pyrido[1,2-a]pyrimidin-3-carbaldehyde) inhibiting vital enzyme of mycobacterium tuberculosis were applied. membrane affinity of the compounds tb803 and tb820 and their p ...	2016	27497074
infection-induced vascular permeability aids mycobacterial growth.	pathogenic mycobacteria trigger formation of organized granulomas. as granulomas mature, they induce angiogenesis and vascular permeability. here, in a striking parallel to tumor pro-angiogenic signaling, we identify angiopoietin-2 (ang-2) induction as an important component of vascular dysfunction during mycobacterial infection. mycobacterial infection in humans and zebrafish results in robust induction of ang-2 expression from macrophages and stromal cells. using a small-molecule inhibitor clo ...	2016	27496976
prevalence of mycobacterium tuberculosis beijing genotype and its association with drug resistance in north india.	the global presence and rapid dissemination of beijing genotype of mycobacterium tuberculosis, makes it an important issue of public health. its presence and association with multi-drug resistance has been shown in many settings. in present study we tried to find its prevalence and association with drug resistance in north india. one hundred and twenty four m. tuberculosis isolates were analyzed with spoligotyping, further drug susceptibility testing was done by 1% proportional method. out of th ...	2016	27496592
clinical significance of smear positivity for acid-fast bacilli after ≥5 months of treatment in patients with drug-susceptible pulmonary tuberculosis.	patients with pulmonary tuberculosis (tb) with acid-fast bacilli (afb)-positive sputum smear at 5 months or later during treatment are considered to be cases of treatment failure according to world health organization guidelines. this study evaluated the proportion, clinical characteristics, and significance of positive sputum smears after ≥5 months of standard treatment in patients with drug-susceptible pulmonary tb.this was a retrospective cohort study of 1611 patients with culture-confirmed d ...	2016	27495111
associations between systemic inflammation, mycobacterial loads in sputum and radiological improvement after treatment initiation in pulmonary tb patients from brazil: a prospective cohort study.	mycobacterium tuberculosis infection is known to cause inflammation and lung tissue damage in high-risk populations. nevertheless, direct associations between mycobacterial loads, systemic inflammation and pulmonary lesions upon treatment initiation have not been fully characterized. in the present exploratory study, we prospectively depict the immune profile, microbial clearance and evolution of radiographic lesions in a pulmonary tuberculosis (ptb) patient cohort before and 60 days after anti- ...	2016	27494953
down-regulation of mir-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting jnk2 in human macrophages.	induction of cell apoptosis is one of the major host defense mechanisms through which macrophages control mycobacterium tuberculosis (mtb) infection. however, the mechanisms underlying macrophage apoptosis triggered by mtb infection are still largely unknown. in this study, a microarray profiling survey revealed 14 mirnas were down-regulated in cd14+ monocytes from active pulmonary tuberculosis patients, and only the reduction of mir-20a-5p could be reversed after successful anti-tuberculosis tr ...	2016	27494776
dual targeting of intracellular pathogenic bacteria with a cleavable conjugate of kanamycin and an antibacterial cell-penetrating peptide.	bacterial infection caused by intracellular pathogens, such as mycobacterium, salmonella, and brucella, is a burgeoning global health epidemic that necessitates urgent action. however, the therapeutic value of a number of antibiotics, including aminoglycosides, against intracellular pathogenic bacteria is compromised due to their inability to traverse eukaryotic membranes. for this significant problem to be addressed, a cleavable conjugate of the antibiotic kanamycin and a nonmembrane lytic, bro ...	2016	27494027
heteroresistance of mycobacterium tuberculosis strains may be associated more strongly with poor treatment outcomes than within-host heterogeneity of m. tuberculosis infection.		2016	27493236
pyrrolidinone and pyrrolidine derivatives: evaluation as inhibitors of inha and mycobacterium tuberculosis.	a series of geq analogues bearing pyrrolidinone or pyrrolidine cores were synthesized and evaluated against inha, essential target for mycobacterium tuberculosis (m.tb) survival. the compounds were also evaluated against m.tb h37rv growth. interestingly, some of the compounds, not efficient as inha inhibitors, are active against m.tb with mics up to 1.4 μm. in particular, compound 4b was screened with different m.tb mutated strains in order to identify the cellular target, but without success, s ...	2016	27490025
multifunctional t cell response to dosr and rpf antigens is associated with protection in long-term mycobacterium tuberculosis-infected individuals in colombia.	multifunctional t cells have been shown to be protective in chronic viral infections. in mycobacterial infections, however, evidence for a protective role of multifunctional t cells remains inconclusive. short-term cultures of peripheral blood mononuclear cells stimulated with the mycobacterium tuberculosis rd1 antigens 6-kda early secretory antigenic target (esat6) and 10-kda culture filtrate antigen (cfp10), which are induced in the early infection phase, have been mainly used to assess t cell ...	2016	27489136
evaluation of semiautomated is6110-based restriction fragment length polymorphism typing for mycobacterium tuberculosis in a high-burden setting.	the manual is6110-based restriction fragment length polymorphism (rflp) typing method is highly discriminatory; however, it is laborious and technically demanding, and data exchange remains a challenge. in an effort to improve is6110-based rflp to make it a faster format, dupont molecular diagnostics recently introduced the is6110-pvuii kit for semiautomated typing of mycobacterium tuberculosis using the riboprinter microbial characterization system. this study aimed to evaluate the semiautomate ...	2016	27487956
crystal structure of rv3899c(184-410), a hypothetical protein from mycobacterium tuberculosis.	rv3899c is a hypothetical protein from mycobacterium tuberculosis which is conserved across mycobacteria. it is predicted to be secreted and has been found in culture filtrates. it has been proposed as a potential vaccine candidate; however, its biological function is unknown. here, the global structure of rv3899c(184-410), a fragment of rv3899c, is reported. the structure resembles the shell of a sea snail, and its n- and c-termini form two relatively independent compact domains: an α/β/α sandw ...	2016	27487929
the use of digital pcr to improve the application of quantitative molecular diagnostic methods for tuberculosis.	real-time pcr (qpcr) based methods, such as the xpert mtb/rif, are increasingly being used to diagnose tuberculosis (tb). while qualitative methods are adequate for diagnosis, the therapeutic monitoring of tb patients requires quantitative methods currently performed using smear microscopy. the potential use of quantitative molecular measurements for therapeutic monitoring has been investigated but findings have been variable and inconclusive. the lack of an adequate reference method and referen ...	2016	27487852
a silicon nitride isfet based immunosensor for ag85b detection of tuberculosis.	a silicon nitride ion sensitive field effect transistor (isfet) based immunosensor was developed as a low-cost and label-free electrical detection for the detection of antigen 85 complex b (ag85b). the sensing membrane of the isfet was modified with 3-aminopropyltriethoxysilane (aptes) followed by glutaraldehyde (ga), yielding an aldehyde-terminated surface. this group is available for immobilization of a monoclonal antibody against a recombinant ag85b protein (anti-ag85b antibody). the optimal ...	2016	27486595
synthesis, characterization, and efficacy of antituberculosis isoniazid zinc aluminum-layered double hydroxide based nanocomposites.	the chemotherapy for tuberculosis (tb) is complicated by its long-term treatment, its frequent drug dosing, and the adverse effects of anti-tb drugs. in this study, we have developed two nanocomposites (a and b) by intercalating the anti-tb drug isoniazid (inh) into zn/al-layered double hydroxides. the average size of the nanocomposites was found to bê164 nm. the efficacy of the zn/al-layered double hydroxides intercalated inh against mycobacterium tuberculosis was increased by approximately thr ...	2016	27486322
rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents.	a series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against mycobacterium tuberculosis h37rv. the binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of m. tuberculosis has been explored. among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 µg/ml) comparable to triclosan. all the synthesized compounds exhibited low levels ...	2016	27486307
lcp1 is a phosphotransferase responsible for ligating arabinogalactan to peptidoglycan in mycobacterium tuberculosis.	mycobacterium tuberculosis, the etiological agent of tuberculosis (tb), has a unique cell envelope which accounts for its unusual low permeability and contributes to resistance against common antibiotics. the main structural elements of the cell wall consist of a cross-linked network of peptidoglycan (pg) in which some of the muramic acid residues are covalently attached to a complex polysaccharide, arabinogalactan (ag), via a unique α-l-rhamnopyranose-(1→3)-α-d-glcnac-(1→p) linker unit. while t ...	2016	27486192
human ulk1 variation and susceptibility to mycobacterium tuberculosis infection.	unlike tuberculosis, few studies have evaluated a host genetic basis for variability in susceptibility to latent mycobacterium tuberculosis infection (ltbi). we performed a candidate gene association study of autophagy-related genes and ltbi.	2016	27485354
research progress in the field of immunotherapeutic vaccination in human tb and the way ahead.		2016	27485072
exosomes derived from tumor cells genetically modified to express mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy.	to examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens.	2016	27484689
mycobacterium tuberculosis h37 rv1222: structural insight in transcription inhibition.		2016	27484221
granulomatous interstitial nephritis associated with influenza a: h1n1 infection--a case report.	the causes of acute tubulointerstitial nephritis can be grouped into four broad categories: medications, infections, immunologic diseases, or idiopathic processes. here we report a 17-year-old female who developed acute kidney injury (aki) due to granulomatous interstitial nephritis (gin) associated with influenza a: h1n1 infection.	2016	27483570
mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9.	cavitation is a key pathological feature of human tuberculosis (tb), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. although cavitation does not occur in conventional mouse strains after inf ...	2016	27482816
identification of mycobacterium tuberculosis adherence-mediating components: a review of key methods to confirm adhesin function.	anti-adhesion therapy represents a potentially promising avenue for the treatment and prevention of tuberculosis in a post-antibiotic era. adhesins are surface-exposed microbial structures or molecules that enable pathogenic organisms to adhere to host surfaces, a fundamental step towards host infection. although several mycobacterium tuberculosis adhesins have been identified, it is predicted that numerous additional adherence-mediating components contribute to the virulence and success of this ...	2016	27482337
transduction of functionally contrasting signals by two mycobacterial ppe proteins downstream of tlr2 receptors.	as pathogen-associated molecular pattern sensors, the tlrs can detect diverse ligands to elicit either proinflammatory or anti-inflammatory responses, but the mechanism that dictates such contrasting immune responses is not well understood. in this work, we demonstrate that proline-proline-glutamic acid (ppe)17 protein of mycobacterium tuberculosis induces tlr1/2 heterodimerization to elicit proinflammatory-type response, whereas ppe18-induced homodimerization of tlr2 triggers anti-inflammatory ...	2016	27481848
neonatal fc receptor regulation of lung immunoglobulin and cd103+ dendritic cells confers transient susceptibility to tuberculosis.	the neonatal fc receptor (fcrn) extends the systemic half-life of igg antibodies by chaperoning bound fc away from lysosomal degradation inside stromal and hematopoietic cells. fcrn also transports igg across mucosal barriers into the lumen, and yet little is known about how fcrn modulates immunity in the lung during homeostasis or infection. we infected wild-type (wt) and fcrn-deficient (fcgrt(-/-)) mice with pseudomonas aeruginosa or mycobacterium tuberculosis to investigate whether recycling ...	2016	27481246
glutamate racemase is the primary target of β-chloro-d-alanine in mycobacterium tuberculosis.	the increasing global prevalence of drug resistance among many leading human pathogens necessitates both the development of antibiotics with novel mechanisms of action and a better understanding of the physiological activities of preexisting clinically effective drugs. inhibition of peptidoglycan (pg) biosynthesis and cross-linking has traditionally enjoyed immense success as an antibiotic target in multiple bacterial pathogens, except in mycobacterium tuberculosis, where it has so far been unde ...	2016	27480853
mycobacterium tuberculosis gene expression at different stages of hypoxia-induced dormancy and upon resuscitation.	the physiology of dormant mycobacterium tuberculosis was studied in detail by examining the gene expression of 51 genes using quantitative reverse-transcription polymerase chain reaction. a forty-day period of dormancy in the wayne culture model depicted four major transcription patterns. some sigma factors and many metabolic genes were constant, whereas genes belonging to the dormancy regulon were activated on day 9. in particular, alpha-crystallin mrna showed more than a 1,000-fold increase co ...	2016	27480637
the α/β hydrolase fold proteins of mycobacterium tuberculosis, with reference to their contribution to virulence.	the α/β hydrolase fold superfamily is an ancient and widely diversified group of primarily hydrolytic enzymes. in this review, the adaptations of these proteins to the pathogenic lifestyle of mycobacterium tuberculosis (mtb), the causative agent of tuberculosis, are examined. of the 105 α/β hydrolases identified in mtb, many are associated with lipid metabolism, particularly in the biosynthesis and maintenance of the mtb's unique cell envelope, as well in the large number of extracellular lipase ...	2016	27480283
bioautography with tlc-ms/nmr for rapid discovery of anti-tuberculosis lead compounds from natural sources.	while natural products constitute an established source of lead compounds, the classical iterative bioassay-guided isolation process is both time- and labor-intensive and prone to failing to identify active minor constituents. (hp)tlc-bioautography-ms/nmr, which combines cutting-edge microbiological, chromatographic, and spectrometric technologies, was developed to accelerate anti-tuberculosis (tb) drug discovery from natural sources by acquiring structural information at a very early stage of t ...	2016	27478868
mycobacterial protein tyrosine phosphatases a and b inhibitors augment the bactericidal activity of the standard anti-tuberculosis regimen.	novel drugs are required to shorten the duration of treatment for tuberculosis (tb) and to combat the emergence of drug resistance. one approach has been to identify and target mycobacterium tuberculosis (mtb) virulence factors, which promote the establishment of tb infection and pathogenesis. mtb produces a number of virulence factors, including two protein tyrosine phosphatases (ptps), mptpa and mptpb, to evade the antimicrobial functions of host macrophages. to assess the therapeutic potentia ...	2016	27478867
interferon-gamma improves macrophages function against m. tuberculosis in multidrug-resistant tuberculosis patients.	background. mycobacterium tuberculosis (m. tuberculosis) that causes tuberculosis (tb) kills millions of infected people annually especially multidrug-resistant tuberculosis (mdr-tb). on infection, macrophages recognize the mycobacteria by toll-like receptor (tlr) followed by phagocytosis and control of mycobacteria. in addition, macrophages also secrete il-12 to induce ifn-γ production by t, which, in turn, increases the phagocytosis and oxidative burst. individuals with defects in innate or ad ...	2016	27478636
phenotypic analysis of peripheral b cell populations during mycobacterium tuberculosis infection and disease.	mycobacterium tuberculosis (mtb) remains an unresolved threat resulting in great annual loss of life. the role of b cells during the protective immunity to mtb is still unclear. b cells have been described as effector cells in addition to their role as antibody producing cells during disease. here we aim to identify and characterize the frequency of peripheral b-cell subpopulations during active tuberculosis and over treatment response. analysis were done for both class switched (cs) and non-cla ...	2016	27478412
mycobacterium tuberculosis and prosthetic joint infection.		2016	27477982
mycobacterium tuberculosis and prosthetic joint infection.		2016	27477980
design and development of new class of mycobacterium tuberculosisl-alanine dehydrogenase inhibitors.	mycobacterium tuberculosisl-alanine dehydrogenase (mtb l-aladh) is one of the important drug targets for treating latent/persistent tuberculosis. in this study we used crystal structure of the mtb l-aladh bound with cofactor nad(+) as a structural framework for virtual screening of our in-house database to identified new classes of l-aladh inhibitor. we identified azetidine-2,4-dicarboxamide derivative as one of the potent inhibitor with ic50 of 9.22±0.72μm. further lead optimization by synthesi ...	2016	27477207
evolution of mycobacterium tuberculosis and implications for vaccine development.	tuberculosis (tb) is a growing public health threat, particularly in the face of the global epidemics of multidrug resistance. given the limited efficacy of the current tb vaccine and the recent clinical failure of the most advanced new tb vaccine candidate, novel concepts for vaccine design should be explored. most t cell antigens in the human-adapted mycobacterium tuberculosis complex (mtbc) are evolutionarily conserved and under strong purifying selection, indicating that host immune response ...	2016	27476231
a convenient synthesis and screening of benzosuberone bearing 1,2,3-triazoles against mycobacterium tuberculosis.	a series of benzosuberone bearing 1,2,3-triazoles were rationally designed and alkyl/aryl groups appended on 1,2,3-triazole derivatives 5a-o were synthesized using click chemistry and evaluated for their in vitro antimycobacterial activity against mycobacterium tuberculosis h37rv (atcc27294). compounds 5h (mic: 3.125μg/ml) and 5l, 5m, 5o (mic: 6.25μg/ml) exhibited promising hits. this is the first letter on the synthesis and in vitro antimycobacterial activity against mycobacterium tuberculosis ...	2016	27476139
repurposing of a drug scaffold: identification of novel sila analogues of rimonabant as potent antitubercular agents.	the structural similarity between an mmpl3 inhibitor bm212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against mycobacterium tuberculosis (h37rv). the sila analogue 18a was found to be the most potent antimycobacterial compound (mic, 3 ...	2016	27476117
the active site architecture in peroxiredoxins: a case study on mycobacterium tuberculosis ahpe.	peroxiredoxins catalyze the reduction of peroxides, a process of vital importance to survive oxidative stress. a nucleophilic cysteine, also known as the peroxidatic cysteine, is responsible for this catalytic process. we used the mycobacterium tuberculosis alkyl hydroperoxide reductase e (mtahpe) as a model to investigate the effect of the chemical environment on the specificity of the reaction. using an integrative structural (r116a - pdb ; f37h - pdb ), kinetic and computational approach, we ...	2016	27471753
surgical aspects of pulmonary tuberculosis: an update.	tuberculosis remains a major global medical challenge and concern. in the world's population of over 7.4 billion people, 8.6 million are estimated to be infected with mycobacterium tuberculosis; another 2.2 billion have latent tuberculosis. there is an annual incidence of 16,000 new cases in the usa and 7-8 million new cases worldwide, of which 440,000 are multidrug-resistant or extensively multidrug-resistant, mainly in developing countries or emerging economies. according to the world health o ...	2016	27471312
evaluation of quantiferon-tb gold plus for detection of mycobacterium tuberculosis infection in japan.	performance of interferon-γ (ifn-γ) release assays still needs to be improved. the data on the performance of quantiferon-tb gold plus (qft-plus), a new-generation of qft assay are limited. this study evaluated the diagnostic performance of qft-plus, and compared to that of quantiferon-tb gold in-tube (qft-git). blood samples were collected from 162 bacteriologically confirmed tuberculosis (tb) patients and 212 mycobacterium tuberculosis-uninfected volunteers; these samples were then tested with ...	2016	27470684
draft genome sequence of the mycobacterium tuberculosis complex pathogen m. mungi, identified in a banded mongoose (mungos mungo) in northern botswana.	mycobacterium mungi, a mycobacterium tuberculosis complex pathogen, has emerged in banded mongoose in northern botswana and northwest zimbabwe. the pathogen is transmitted through infected secretions used in olfactory communication behavior (k. a. alexander, c. e. sanderson, m. h. larsen, s. robbe-austerman, m. c. williams, and m. v. palmer, mbio 7(3):e00281-16, 2016, http://dx.doi.org/10.1128/mbio.00281-16). we announce here the draft genome sequence of this emerging pathogen.	2016	27469947
loperamide restricts intracellular growth of mycobacterium tuberculosis in lung macrophages.	new approaches for improving tuberculosis (tb) control using adjunct host-directed cellular and repurposed drug therapies are needed. autophagy plays a crucial role in the response to tb, and a variety of autophagy-inducing drugs that are currently available for various medical conditions may serve as an adjunct treatment in pulmonary tb. here, we evaluated the potential of loperamide, carbamazepine, valproic acid, verapamil, and rapamycin to enhance the antimicrobial immune response to mycobact ...	2016	27468130
cd4+ t cells recognizing pe/ppe antigens directly or via cross reactivity are protective against pulmonary mycobacterium tuberculosis infection.	mycobacterium tuberculosis (mtb), possesses at least three type vii secretion systems, esx-1, -3 and -5 that are actively involved in pathogenesis and host-pathogen interaction. we recently showed that an attenuated mtb vaccine candidate (mtb δppe25-pe19), which lacks the characteristic esx-5-associated pe/ppe genes, but harbors all other components of the esx-5 system, induces cd4+ t-cell immune responses against non-esx-5-associated pe/ppe protein homologs. these t cells strongly cross-recogni ...	2016	27467705
detection of mycobacterium tuberculosis complex in paraffin-embedded tissues by the new automated abbott realtime mtb assay.	the abbott realtime mtb assay, launched in june 2014, has been shown to have a competitive performance in the detection of the mycobacterium tuberculosis (mtb) complex in respiratory specimens. the present study was conducted to investigate the usefulness of the abbott mtb realtime assay in the detection of mtb in formalin-fixed paraffin-embedded (ffpe) tissues.	2016	27466302
mycobacterium tuberculosis lineages and anti-tuberculosis drug resistance in reference hospitals across viet nam.	mycobacterium tuberculosis, the tuberculosis (tb) pathogen, despite a low level of genetic diversity, has revealed a high variety of biological and epidemiological characteristics linked to their lineages, such as transmissibility, fitness and propensity to acquire drug resistance. this has important implications for the epidemiology of tb. we conducted this first countrywide cross-sectional study to identify the prevalent m. tuberculosis lineages and to assess their epidemiological associations ...	2016	27464737
granulomatous responses in hiv and mycobacterium tuberculosis coinfection.		2016	27462091
inflammasome activation and function during infection with mycobacterium tuberculosis.	tuberculosis (tb) is caused by infection with mycobacterium tuberculosis (mtb) and represents one of the most relevant bacterial diseases worldwide. recent advances have yielded new insights into the molecular basis of the immune response required for restriction of the pathogen and also highlighted determinants of immunopathology in tb. several innate immune mediators including soluble proteins as well as lipid molecules participate in both processes, and their mechanisms of action during tb ha ...	2016	27460810
genotypic characterization of drug resistant mycobacterium tuberculosis in quebec, 2002-2012.	the increasing emergence of drug-resistant tuberculosis presents a threat to the effective control of tuberculosis (tb). rapid detection of drug-resistance is more important than ever to address this scourge. the purpose of this study was to genotypically characterize the first-line antitubercular drug-resistant isolates collected over 11 years in quebec.	2016	27459848
correction for molina-moya et al., evaluation of genoflow dr-mtb array test for detection of rifampin and isoniazid resistance in mycobacterium tuberculosis.		2016	27458275
amikacin optimal exposure targets in the hollow-fiber system model of tuberculosis.	aminoglycosides such as amikacin are currently used for the treatment of multidrug-resistant tuberculosis (mdr-tb). however, formal pharmacokinetic/pharmacodynamic (pk/pd) studies to identify amikacin exposures and dosing schedules that optimize mycobacterium tuberculosis killing have not been performed. it is believed that aminoglycosides do not work well under acidic conditions, which, if true, would mean poor sterilizing activity against semidormant bacilli at low ph. we performed time-kill s ...	2016	27458215
comparison of maldi-tof ms, nucleic acid hybridization and the mpt64 immunochromatographic test for the identification of m. tuberculosis and non-tuberculosis mycobacterium species.	mycobacteria are an important cause of morbidity in humans. rapid and accurate mycobacterial identification is important for improving patient outcomes. however, identification of mycobacterium species is not easy, due to the slow and fastidious growth of mycobacteria. recently, biochemical, sequencing, and probing methods have come to be used for identification. this study compared the performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) for ...	2016	27551724
hypoxia and classical activation limits mycobacterium tuberculosis survival by akt-dependent glycolytic shift in macrophages.	cellular reactive oxygen species (ros) is a major antibacterial defense mechanism used by macrophages upon activation. exposure of mycobacterium tuberculosis (mtb)-infected macrophages to hypoxia is known to compromise the survival of the pathogen. here we report that the hypoxia-induced control of intracellular mtb load in raw 264.7 macrophages was mediated by regulating the cellular ros levels. we show that similar to classical activation, hypoxia incubation of macrophages resulted in decrease ...	2016	27551515
early bactericidal activity of azd5847 in patients with pulmonary tuberculosis.	azd5847 is an oxazolidinone antibiotic with in vitro activity against mycobacterium tuberculosis the objective of this study was to evaluate the antimycobacterial activity, safety, and pharmacokinetics of azd5847 in patients with pulmonary tuberculosis. groups of 15 treatment-naive, sputum smear-positive adults with pulmonary tuberculosis were randomly assigned to receive azd5847 at one of four doses (500 mg once daily, 500 mg twice daily, 1,200 mg once daily, and 800 mg twice daily) or daily st ...	2016	27550361
hiv-1 tat protein vaccination in mice infected with mycobacterium tuberculosis is safe, immunogenic and reduces bacterial lung pathology.	the therapeutic hiv-1 tat protein vaccine is in advanced clinical development. tuberculosis, the main aids co-infection, is highly endemic in areas where aids prevention through vaccination is needed. however, safety and immunogenicity of tat vaccination in the course of mycobacterium tuberculosis (mtb) infection is still unknown and it prevents the possibility to administer the vaccine to mtb-infected individuals. we addressed the interplay and effects of tat vaccination on mtb infection in imm ...	2016	27549342
direct matrix-assisted laser desorption ionisation time-of-flight mass spectrometry identification of mycobacteria from colonies.	matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (maldi-tof-ms) identification of mycobacteria requires a standard acetonitrile/formic acid pre-maldi-tof-ms. we prospectively compared this standard protocol with direct deposit with matrix for the identification of mycobacteria cultured on solid media. we first verified that mycobacterium tuberculosis was killed after it was mixed with matrix. then, 111 mycobacterium isolates previously identified by partial rpob gene ...	2016	27549109
plastic-chip-based magnetophoretic immunoassay for point-of-care diagnosis of tuberculosis.	tuberculosis (tb) remains a relevant infectious disease in the 21st century, and its extermination is still far from being attained. due to the extreme infectivity of incipient tb patients, a rapid sensing system for proficient point-of-care (poc) diagnostics is required. in our study, a plastic-chip-based magnetophoretic immunoassay (pcmpi) is introduced using magnetic and gold nanoparticles (nps) modified with mycobacterium tuberculosis (mtb) antibodies. this pcmpi offers an ultrasensitive lim ...	2016	27548010
structure of the essential mtb fadd32 enzyme: a promising drug target for treating tuberculosis.	mycolic acids are indispensible lipids of mycobacterium tuberculosis (mtb), the causative agent of tuberculosis (tb), and contribute to the distinctive architecture and impermeability of the mycobacterial cell envelope. fadd32 plays a pivotal role in mycolic acid biosynthesis by functionally linking fatty acid synthase (fas) and polyketide synthase (pks) biosynthetic pathways. fadd32, a fatty acyl-amp ligase (faal), represents one of the best genetically and chemically validated new tb drug targ ...	2016	27547819
new strain multidrug resistant tuberculosis g24767 in puerto rico: old disease a continuous threat.	multidrug resistant tuberculosis (mdr-tb) is defined as a mycobacterium tuberculosis strain resistant to two or more first-line anti-tuberculous drugs. tuberculosis (tb) is a global threat to society despite improvement in therapy as it continues to be an economic burden especially in underdeveloped countries. the downfall of global economics and growing travel destinations in developing countries has escalade the exposure of organism not previously encountered in industrialized nations. most ca ...	2016	27547724
do not feed the wildlife: associations between garbage use, aggression, and disease in banded mongooses (mungos mungo).	urbanization and other human modifications of the landscape may indirectly affect disease dynamics by altering host behavior in ways that influence pathogen transmission. few opportunities arise to investigate behaviorally mediated effects of human habitat modification in natural host-pathogen systems, but we provide a potential example of this phenomenon in banded mongooses (mungos mungo), a social mammal. our banded mongoose study population in botswana is endemically infected with a novel myc ...	2016	27547366
the bcgδbcg1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo.	mycobacterium tuberculosis (mtb) has been a threat to humans since ancient times, and it is the main causative agent of tuberculosis (tb). until today, the only licensed vaccine against mtb is the live attenuated m. bovis bacillus calmette-guérin (bcg), which has variable levels of protection against the pulmonary form of infection. the quest for a new vaccine is a priority given the rise of multidrug-resistant mtb around the world, as well as the tremendous burden imposed by latent tb. the obje ...	2016	27546876
new tests for detection of mycobacterium tuberculosis infection: sufficient to meet the who 2035 targets?		2016	27545599
rifapentine for the treatment of latent tuberculosis.	the goal of this article is to review the use of rifapentine in the treatment of latent tuberculosis infection (ltbi). controlling ltbi is an important part of the global strategy to end the spread of tuberculosis. rifapentine's potent sterilizing effect against mycobacterium tuberculosis combined with its long half-life make it an attractive ltbi treatment option.	2016	27545595
proteomic and morphological changes produced by subinhibitory concentration of isoniazid in mycobacterium tuberculosis.	to study the proteomic and morphological changes in mycobacterium tuberculosis h37rv exposed to subinhibitory concentration of isoniazid (inh).	2016	27545345
strain differentiation of mycobacterium tuberculosis for epidemiology in northwest of iran.	tuberculosis is a major health problem throughout the world and there are still a great number of people with the disease. planning for controlling tuberculosis is required to identify the sources of infection and screening for the disease. the aim of this study is the differentiation of mycobacterium tuberculosis strains for better understands the spread of the disease in north west iran. in this study, 194 positive cultures of m. tuberculosis in north west iran were evaluated by the miru-vntr ...	2016	27545209
binding sites for acylated trehalose analogs of glycolipid ligands on an extended carbohydrate recognition domain of the macrophage receptor mincle.	the macrophage receptor mincle binds to trehalose dimycolate on the surface of mycobacterium tuberculosis signaling initiated by this interaction leads to cytokine production, which underlies the ability of mycobacteria to evade the immune system and also to function as adjuvants. in previous work the mechanism for binding of the sugar headgroup of trehalose dimycolate to mincle has been elucidated, but the basis for enhanced binding to glycolipid ligands, in which hydrophobic substituents are a ...	2016	27542410
genotypic detection of rpob and katg gene mutations associated with rifampicin and isoniazid resistance in mycobacterium tuberculosis isolates: a local scenario (kelantan).	drug resistant tuberculosis (dr-tb) remains a public health issue that is of major concern on a global scale. the characterisation of clinical isolates may provide key information regarding the underlying mechanisms of drug resistance, and helps to augment therapeutic options. this study aims to evaluate the frequency of gene mutations associated with rifampicin (rif) and isoniazid (inh) resistance among nine clinical isolates.	2016	27540322
corrigendum to "katg ser315 and rpob 81-bp hotspot region substitutions: reliability for detection of drug-resistant strains of mycobacterium tuberculosis" [j. global antimicrob. resist. 5 (2016) 92-93].		2016	27553705
safety and immunogenicity of the m72/as01e candidate tuberculosis vaccine in adults with tuberculosis: a phase ii randomised study.	previous studies have shown that the m72/as01e candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and mycobacterium tuberculosis-infected adults. this phase ii, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of m72/as01e in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13) ...	2016	27553419
loop-mediated isothermal amplification (lamp) assay for speedy diagnosis of tubercular lymphadenitis: the multi-targeted 60-minute approach.	tuberculous lymphadenitis (tbla), the most common presentation of tuberculosis, poses a significant diagnostic challenge in the developing countries. timely, accurate and cost-effective diagnosis can decrease the high morbidity associated with tbla especially in resource-poor high-endemic regions. the loop-mediated isothermal amplification assay (lamp), using two targets, was evaluated for the diagnosis of tbla.	2016	27553418
dissecting host factors that regulate the early stages of tuberculosis infection.	incomplete understanding of mechanisms involved in the host-pathogen interactions constrains our efforts to eliminate tuberculosis. in many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. to identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. here, human pbmcs were infected with live mycobacterium tuberculosis in culture, and the appearance of granuloma- ...	2016	27553417
micrococcin p1 - a bactericidal thiopeptide active against mycobacterium tuberculosis.	the lack of proper treatment for serious infectious diseases due to the emergence of multidrug resistance reinforces the need for the discovery of novel antibiotics. this is particularly true for tuberculosis (tb) for which 3.7% of new cases and 20% of previously treated cases are estimated to be caused by multi-drug resistant strains. in addition, in the case of tb, which claimed 1.5 million lives in 2014, the treatment of the least complicated, drug sensitive cases is lengthy and disagreeable. ...	2016	27553416
sputum is a surrogate for bronchoalveolar lavage for monitoring mycobacterium tuberculosis transcriptional profiles in tb patients.	pathogen-targeted transcriptional profiling in human sputum may elucidate the physiologic state of mycobacterium tuberculosis (m. tuberculosis) during infection and treatment. however, whether m. tuberculosis transcription in sputum recapitulates transcription in the lung is uncertain. we therefore compared m. tuberculosis transcription in human sputum and bronchoalveolar lavage (bal) samples from 11 hiv-negative south african patients with pulmonary tuberculosis. we additionally compared these ...	2016	27553415
immunoglobulin g response to mammalian cell entry 1a (mce1a) protein as biomarker of active tuberculosis.	cell wall components are major determinants of virulence of mycobacterium tuberculosis and they contribute to the induction of both humoral and cell-mediated immune response. the mammalian cell entry protein 1a (mce1a), in the cell wall of m. tuberculosis, mediates entry of the pathogen into mammalian cells. here, we examined serum immunoglobulin levels (iga, igm and total igg) against mce1a as a potential biomarker for diagnosis and monitoring tuberculosis (tb) treatment response. serum samples ...	2016	27553414
a snapshot of the predominant single nucleotide polymorphism cluster groups of mycobacterium tuberculosis clinical isolates in delhi, india.	several attempts have been made to associate phylogenetic differences among mycobacterium tuberculosis strains to variations in the clinical outcome of the disease and to drug resistance. we genotyped 139 clinical isolates of m. tuberculosis obtained from patients of pulmonary tuberculosis in north delhi region. the isolates were analyzed using nine single nucleotide polymorphism (snp) markers, spoligotyping and miru-vntrs; and the results were correlated with their drug susceptibility profile. ...	2016	27553413
mmpl transporter-mediated export of cell-wall associated lipids and siderophores in mycobacteria.	mycobacteria produce a large variety of surface-exposed lipids with unusual structures. some of these compounds are ubiquitously present in mycobacteria and play an important role in the structural organization of the cell envelope, while others are species-specific. the biosynthesis of most of these lipids requires modular polyketide synthases (pks) or non-ribosomal peptide synthetases (nrps) that are intracellular, suggesting that the assembly of these compounds takes place in the cytosolic co ...	2016	27553408
comparative study of enzymatic activities of new katg mutants from low- and high-level isoniazid-resistant clinical isolates of mycobacterium tuberculosis.	resistance to isoniazid (inh-r) in mycobacterium tuberculosis is mainly due to mutations at position 315 (s315t) of the catalase-peroxidase katg. we identified 16 mutations (including 13 biochemically uncharacterized mutations) in katg from inh-r clinical isolates of m. tuberculosis showing mutations other than s315t. the katg enzymatic activities (catalase, peroxidase, free radical production and isonicotinoyl-nad formation) of wild-type katg and the 16 mutants were determined and correlated to ...	2016	27553406
evaluation of multiplex pcr using mpb64 and is6110 primers for rapid diagnosis of tuberculous meningitis.	tuberculous meningitis (tbm) is one of those most serious manifestations of extra-pulmonary tuberculosis and prompt diagnosis and treatment is required for better clinical outcome. it is difficult to diagnose due to lack of rapid, sensitive, and specific tests. newer methods, which are easy and reliable, are required to diagnose tbm at an early stage. thus our aim was to evaluate the multiplex polymerase chain reaction (pcr) technique, using primers directed against the insertion sequence is6110 ...	2016	27553404
tuberculosis and its management: an overview.	tuberculosis (tb) is a primordial infectious disease that mainly affects the lungs. mycobacterium tuberculosis (m. tuberculosis) is the etiological agent of tb and currently more than one-third of the world population is suffering from tb. for the treatment of tb, administration of multiple antibiotics such as isoniazid, rifampicin, pyrazinamide and ethambutol is required for long time period to kill the bacteria. therefore antibiotic resistance is the emerging problem in multiple drug-resistant ...	2016	27553018
the role of prostate apoptosis response-4 (par-4) in mycobacterium tuberculosis infected macrophages.	prostate apoptosis response-4 (par-4) is a tumor suppressor protein that forms a complex with glucose-regulated protein 78 (grp78) to induce apoptosis. previously, we reported that er stress-induced apoptosis is a critical host defense mechanism against mycobacterium tuberculosis (mtb). we sought to understand the role of par-4 during er stress-induced apoptosis in response to mycobacterial infection. par-4 and grp78 protein levels increased in response mtb (strain: h37ra) infection. furthermore ...	2016	27552917
tuberculosis screening: an update for nps.	one-third of the world's population is infected with mycobacterium tuberculosis. if nps are to effectively participate in eliminating and preventing tuberculosis (tb), they must be cognizant of the current cdc-approved tb screening methods and guidelines.	2016	27552684
isolation of alpha-linolenic acid from sutherlandia frutescens and its inhibition of mycobacterium tuberculosis' shikimate kinase enzyme.	sutherlandia frutescens (l) r.br. is one of traditional herbal medicines that formed the basis of primary health care systems since the earliest days and is still widely used. sutherlandia is prescribed for people with tuberculosis (tb), but is still not known which compound(s) acts against m. tuberculosis and its mode of action. the aim of this study was to identify and isolate antimycobacterial compounds from s. frutescens extracts against shikimate kinase, a drug target for m. tuberculosis.	2016	27639973
integration of ligand and structure based approaches for identification of novel mbti inhibitors in mycobacterium tuberculosis and molecular dynamics simulation studies.	mycobacterium tuberculosis is an obligate pathogen of mammals and is responsible for more than two million deaths annually. the ability to acquire iron from the extracellular environment is a key determinant of pathogenicity in mycobacteria. m. tuberculosis acquires iron exclusively through the siderophores. several lines of evidence suggest that siderophores have a critical role in bacterial growth and virulence. hence, in the present study, we have used a combined ligand and structure-based dr ...	2016	27639087
[thoracic manifestation of tuberculosis].	tuberculosis (tb) is a granulomatous disease caused by mycobacterium tuberculosis and transmission is via an airborne route by droplet infection. in the majority of cases patients have thoracic tb, which most frequently presents with hilar lymphadenopathy and pulmonary manifestation. due to the rise in incidence of tb in central europe to be expected over the coming years, it is essential to be acquainted with the radiological manifestations of pulmonary tb, particularly to be able to discrimina ...	2016	27638823
molecular characterization of multidrug-resistant mycobacterium tuberculosis isolates from high prevalence tuberculosis states in mexico.	mexico is one of the most important contributors of multidrug resistance tuberculosis (mdr-tb) in latin-america, however little is known about the molecular characteristics of these strains. for this reason, the objective of this work was to determine the genotype and characterize polymorphisms in genes associated with resistance to rifampicin, isoniazid, and second-line drugs in isolates from two regions of mexico with high prevalence of drug resistant tuberculosis. clinical isolates from indiv ...	2016	27637930
lack of response to hbha in hiv-infected patients with latent tuberculosis infection.	heparin-binding haemagglutinin (hbha) has been proposed as an immunological biomarker for discriminating active tuberculosis (tb) from latent tb infection (ltbi) and to identify those at higher risk of progressing to active disease. few data are available in immune-compromised patients, which are those with increased risk of tb reactivation. the aim of this stusy was to evaluate the immune response to hbha in hiv-infected subjects with ltbi (hiv-ltbi) or active tb (hiv-tb) in comparison with the ...	2016	27636597
n-alkoxyphenylhydroxynaphthalenecarboxamides and their antimycobacterial activity.	a series of nineteen n-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers n-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. primary in vitro screening of all the synthesized compounds was performed against mycobacterium tuberculosis h37ra, m. kansasii and m. smegmatis. screening of the cytotoxicity of the compounds was performed using human monocytic leukemia thp-1 cells. some of the tested compounds showed ant ...	2016	27537867
polishing surgical metal pieces, granulomatosis and mineralogical analysis.	this report describes the case of a 44-year-old man with pulmonary nodules whose histological analysis initially suggested tuberculosis. the mycobacterium tuberculosis (mt) culture was negative and a questionnaire revealed a professional activity of brushing and polishing surgical instruments without any protection for 7 years. a mineralogical analysis by optical and electron microscopy was performed on both a healthy lung tissue biopsy and a lung nodule in a paraffin block. electron microscopy ...	2016	27537720