Publications

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crystal structures of the co and nobound doss gaf-a domain and implications for doss signaling in mycobacterium tuberculosis.doss is a sensor in mycobacterium tuberculosis that differentially responds to o2, no, and co, as well as to changes in the redox state of the prosthetic heme iron atom. the ferrous protein and its fe(ii)no and fe(ii)co complexes undergo autophosphorylation and subsequently transfer the phosphate group to dosr, a nuclear factor, to activate it. in contrast, autophosphorylation is negligible with the ferric protein and the fe(ii)o2 complex. to clarify the basis for this differential response to g ...201627729224
correlation of clinical, laboratory and drug susceptibility profiles in 176 patients with culture positive tbm in a tertiary neurocare centre.drug resistance has increased the difficulties in control of tuberculosis infection. the present study evaluated the clinical and laboratory features among tuberculous meningitis (tbm) patients and the drug susceptibility of mycobacterium tuberculosis (m.tb) isolated from csf. out of 698 csf samples, 176 (25.21%) were m.tb culture positive. among the clinical signs and symptoms, fever, headache and altered sensorium were found to be statistically significant (p<0.05). elisa was a better predicto ...201627717649
performance of the genotype mtbdrplus assay (v2.0) and a new extended genotype mtbdrsl assay (v2.0) for the molecular detection of multi- and extensively drug-resistant mycobacterium tuberculosis on isolates primarily from lithuania.the emergence of extensively drug-resistant tuberculosis (xdr-tb) hampers infection control. to assess the performance of an extended rapid novel molecular analysis for the detection of resistance conferring mutations to fluoroquinolones (gyra, gyrb genes) and aminoglycosides/cyclic peptides (16s rrna rrs gene, eis promotor region) compared to phenotypic susceptibility and sequencing, 43 multidrug-resistant (mdr) and 10 susceptible clinical isolates were analyzed. results were compared to a prev ...201627641092
rewiring cellular metabolism via the akt/mtor pathway contributes to host defence against mycobacterium tuberculosis in human and murine cells.cells in homeostasis metabolize glucose mainly through the tricarboxylic acid cycle and oxidative phosphorylation, while activated cells switch their basal metabolism to aerobic glycolysis. in this study, we examined whether metabolic reprogramming toward aerobic glycolysis is important for the host response to mycobacterium tuberculosis (mtb). through transcriptional and metabolite analysis we show that mtb induces a switch in host cellular metabolism toward aerobic glycolysis in human peripher ...201627624090
interactions of linezolid and second-line anti-tuberculosis agents against multidrug-resistant mycobacterium tuberculosis in vitro and in vivo.the objectives of this study were to evaluate the interactions between linezolid (lzd) and second-line anti-tuberculosis (tb) agents in susceptible and multidrug-resistant (mdr) tb in vitro, and to validate the in vitro results in a murine tb model.201627613365
effective antigen presentation to helper t cells by human eosinophils.although eosinophils are inflammatory cells, there is increasing attention on their immunomodulatory roles. for example, murine eosinophils can present antigen to cd4(+) t helper (th) cells, but it remains unclear whether human eosinophils also have this ability. this study determined whether human eosinophils present a range of antigens, including allergens, to activate th cells, and characterized their expression of mhc class ii and co-stimulatory molecules required for effective presentation. ...201627502559
purification and structural characterization of mce4a from mycobacterium tuberculosis.the mce4a gene of mycobacterium tuberculosis encodes a 400 amino acid residues protein of 43kda, which is a mammalian cell entry protein (mce4a) and plays important role in host cell invasion. mce4a helps in long-term survival of m. tuberculosis by cholesterol utilization. host cholesterol utilization mechanism by mce4a is not clearly understood. in order to investigate the role of mce4a in m. tuberculosis pathogenesis, we purified the recombinant protein by affinity chromatography, analyzed by ...201627355757
diverse drug-resistant subpopulations of mycobacterium tuberculosis are sustained in continuous culture.drug resistance to tuberculosis (tb) has become more widespread over the past decade. as such, understanding the emergence and fitness of antibiotic-resistant subpopulations is crucial for the development of new interventions. here we use a simple mathematical model to explain the differences in the response to isoniazid (inh) of mycobacterium tuberculosis cells cultured under two growth rates in a chemostat. we obtain posterior distributions of model parameters consistent with data using a mark ...201627807274
miliary tuberculosis in an immunocompetent male with a fatal outcome.a man aged 33 years, born in nepal, but resident in the uk for 7 years presented to the emergency department with a 4-day history of general malaise, fever (temperature 38.6°c) and a non-productive cough. his medical history was unremarkable and no high-risk behaviour was identified. clinical examination confirmed decreased air entry bilaterally with bibasal crackles. he was tachycardic, with a heart rate of 120 bpm. further investigation with a 12-lead ecg confirmed supraventricular tachycardia ...201627807020
progress in resistance mechanisms and diagnosis of non-first line anti-tb drugs.tuberculosis (tb) is one of the three major infectious diseases in china and all over the world. in 2014, for the first time, tb killed more people than hiv did. non-first line anti-tb drugs are used as main drugs in the treatment of mdr-tb. however, mdr-tb can gradually develop as extensively drug-resistant tb (xdr-tb) because of poor diagnosis, the unreasonable treatment, poor medical conditions and so on. the death rate of xdr-tb is close to lung cancer. research on the mechanism of drug resi ...201627806934
mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis.tuberculosis, caused by the pathogen mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. it is still a global-health threat, particularly because of the drug-resistant forms. fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. however, their widespread use has led to bacterial resistance. the molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as dna gyrase mutations, ...201627806933
progress on mechanism of ethambutol resistance in mycobacterium tuberculosis.the occurance and prevalence of multidrug-resistant tuberculosis poses a serious threat to the global tuberculosis control. ethambutol (emb) is one of the first-line anti-tuberculosis drugs, which is usually used in combination with isoniazid and rifampicin for treating pan-sensitive tuberculosis, and it can also be used in drug-resistant tuberculosis. however, the situation of emb resistance is alarmingly high, especially in multi-drug resistant tuberculosis. in china, emb resistance rate in th ...201627806932
in silico region of difference (rd) analysis of mycobacterium tuberculosis complex from sequence reads using rd-analyzer.whole-genome sequencing is increasingly used in clinical diagnosis of tuberculosis and study of mycobacterium tuberculosis complex (mtc). mtc consists of several genetically homogenous mycobacteria species which can cause tuberculosis in humans and animals. regions of difference (rds) are commonly regarded as gold standard genetic markers for mtc classification.201627806686
human isotype-dependent inhibitory antibody responses against mycobacterium tuberculosis.accumulating evidence from experimental animal models suggests that antibodies play a protective role against tuberculosis (tb). however, little is known about the antibodies generated upon mycobacterium tuberculosis (mtb) exposure in humans. here, we performed a molecular and functional characterization of the human b-cell response to mtb by generating recombinant monoclonal antibodies from single isolated b cells of untreated adult patients with acute pulmonary tb and from mtb-exposed healthca ...201627729388
c-type lectin receptors in tuberculosis: what we know.mycobacterium tuberculosis (mtb), the etiologic agent of tuberculosis (tb), is recognized by a number of pathogen recognition receptors (prrs), either soluble or predominantly expressed on the surface of various cells of innate and adaptive immunity. c-type lectin receptors (ctlrs) are a class of prrs which can recognize a variety of endogenous and exogenous ligands, thereby playing a crucial role in immunity, as well as in maintaining homeostasis. mtb surface ligands, including mannose-capped l ...201627469378
adenovirally-induced polyfunctional t cells do not necessarily recognize the infected target: lessons from a phase i trial of the aeras-402 vaccine.the development of a vaccine for mycobacterium tuberculosis (mtb) has been impeded by the absence of correlates of protective immunity. one correlate would be the ability of cells induced by vaccination to recognize the mtb-infected cell. aeras-402 is a replication-deficient serotype 35 adenovirus containing dna expressing a fusion protein of mtb antigens 85a, 85b and tb10.4. we undertook a phase i double-blind, randomized placebo controlled trial of vaccination with aeras-402 following bcg. ana ...201627805026
fragment-based approaches to tb drugs.tuberculosis is an infectious disease associated with significant mortality and morbidity worldwide, particularly in developing countries. the rise of antibiotic resistance in mycobacterium tuberculosis (mtb) urgently demands the development of new drug leads to tackle resistant strains. fragment-based methods have recently emerged at the forefront of pharmaceutical development as a means to generate more effective lead structures, via the identification of fragment molecules that form weak but ...201627804891
microrna-20a inhibits autophagic process by targeting atg7 and atg16l1 and favors mycobacterial survival in macrophage cells.autophagy plays important roles in the host immune response against mycobacterial infection. mycobacterium tuberculosis (m. tuberculosis) can live in macrophages owing to its ability to evade attacks by regulating autophagic response. micrornas (mirnas) are small noncoding, endogenously encoded rna which plays critical roles in precise regulation of macrophage functions. whether mirnas specifically influence the activation of macrophage autophagy during m. tuberculosis infection are largely unkn ...201627803889
genetic-and-epigenetic interspecies networks for cross-talk mechanisms in human macrophages and dendritic cells during mtb infection.tuberculosis is caused by mycobacterium tuberculosis (mtb) infection. mtb is one of the oldest human pathogens, and evolves mechanisms implied in human evolution. the lungs are the first organ exposed to aerosol-transmitted mtb during gaseous exchange. therefore, the guards of the immune system in the lungs, such as macrophages (mϕs) and dendritic cells (dcs), are the most important defense against mtb infection. there have been several studies discussing the functions of mϕs and dcs during mtb ...201627803888
tuberculosis and transplantation.mycobacterium tuberculosis is a major opportunistic pathogen in transplant recipients. compared to that in the general population, the frequency of tuberculosis (tb) is 10 to 40 times higher in hematopoietic stem cell transplant (hsct) recipients and 20 to 74 times higher in solid-organ transplant (sot) recipients. transplant recipients with tb are also more likely to develop disseminated disease, have longer time to definitive diagnosis, require more invasive diagnostic procedures, and experien ...201627809952
detection of latent tuberculosis infection among migrant farmworkers along the us-mexico border.migrant farmworkers are among the highest-risk populations for latent tb infection (ltbi) in the united states with numerous barriers to healthcare access and increased vulnerability to infectious diseases. ltbi is usually diagnosed on the border using the tuberculin skin test (tst). quantiferon-tb gold in-tube (qft-git) also measures immune response against specific mycobacterium tuberculosis antigens. the objective of this study is to assess the comparability of tst and qft-git to detect ltbi ...201627809805
immunogenicity and therapeutic effects of pvax1- rv1419 dna from mycobacterium tuberculosis.background the situation of tuberculosis (tb) is very severe in china. new therapeutic agents and regimens to treat tb are urgently needed. objective in this study, a dna vaccine expressing mycobacterium tuberculosis (mtb) rv1419 antigen was constructed and its immunogenicity and therapeutic effects were evaluated. method normal mice and tb model mice were immunized intramuscularly three times at two-week intervals with saline, plasmid vector pvax1, m. vaccae vaccine, pvax1- ag85a (rv3804c) dna ...201627809753
chemical mechanism of the branched-chain aminotransferase ilve from mycobacterium tuberculosis.the biosynthetic pathway of the branched-chain amino acids is essential for mycobacterium tuberculosis growth and survival. we report here the kinetic and chemical mechanism of the pyridoxal 5'-phosphate (plp)-dependent branched-chain aminotransferase, ilve, from m. tuberculosis (mtilve). this enzyme is responsible for the final step of the synthesis of the branched-chain amino acids isoleucine, leucine, and valine. as seen in other aminotransferases, mtilve displays a ping-pong kinetic mechanis ...201627780341
recent advances and structural features of enoyl-acp reductase inhibitors of mycobacterium tuberculosis.mycobacterium tuberculosis enoyl-acp reductase (inha) has been validated as a promising target for antitubercular agents. isoniazid (inh), the most prescribed drug to treat tuberculosis (tb), inhibits a nadh-dependent inha that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. it is a pro-drug that needs activation to form the inhibitory inh-nad adduct by katg coding for catalase-peroxidase. the inh resistance of m. tuberculosis is caused by mutations in ...201627775177
comparative study of kanamycin sulphate microparticles and nanoparticles for intramuscular administration: preparation in vitro release and preliminary in vivo evaluation.kanamycin sulphate (ks) is a mycobacterium tuberculosis protein synthesis inhibitor. ks is polycationic, a property responsible for ks poor oral absorption half-life (2.5 h) and rapid renal clearance, which results in serious nephrotoxicity/ototoxicity. the current study aimed to develop ks-loaded plga vitamin-e-tpgs microparticles (mps) and nanoparticles (nps) to reduce the dosing frequency and dose-related adverse effect. in vitro release was sustained up to 10 days for ks plga-tpgs mps and 13 ...201627733086
anti-tubercular peptides: a quest of future therapeutic weapon to combat tuberculosis.tuberculosis (tb) is a symbolic menace to mankind, infecting almost one third of the world's populace and causing over a million mortalities annually. mycobacterium tuberculosis (mtb) is the key pathogen of tb that invades and replicates inside the host's macrophage. with the emerging dilemma of multi-drug resistant tuberculosis (mdr-tb) and extensively-drug resistant tuberculosis (xdr-tb), the exigency for developing new tb drugs is an obligation now for worldwide researchers. among the propiti ...201627890360
in-silico characterization of a hypothetical protein, rv1288 of mycobacterium tuberculosis containing an esterase signature and an uncommon lyte domain.death toll due to tuberculosis is still rising day by day. whole genome sequence of mycobacterium tuberculosis has provided a platform to conduct research in order to identify the probable drug target.201627890013
tuberculosis caused by mycobacterium orygis in dairy cattle and captured monkeys in bangladesh: a new scenario of tuberculosis in south asia.mycobacterium orygis, commonly known as the oryx bacillus and a newly proposed mycobacterium tuberculosis complex subspecies, was isolated from 18 cattle in a dairy farm and two captured rhesus monkeys in a zoo in bangladesh. all the infected animals had tuberculosis lesions in their lungs, suggesting transmission and infection with m. orygis by an airborne route. the 20 isolates were analysed using a range of conventional and molecular typing methods, and rd-deletion typing and sequencing of se ...201627888587
additional synthesis on thiophene-containing trisubstituted methanes (trsms) as inhibitors of m. tuberculosis and 3d-qsar studies.we earlier reported thiophene-containing trisubstituted methanes (trsms) as novel cores carrying anti-tubercular activity, and identified s006-830 as the phenotypic lead with potent bactericidal activity against single- and multi-drug resistant clinical isolates of mycobacterium tuberculosis (m. tb). in this work, we carried out additional synthesis of several trsms. the reaction scheme essentially followed the grignard reaction and friedel-crafts alkylation, followed by insertion of a dialkylam ...201627885861
mycobacterium tuberculosis-triggered hippo pathway orchestrates cxcl1/2 expression to modulate host immune responses.mycobacterium tuberculosis (mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. here, we demonstrate that hippo (mammalian sterile 20-like 1 and 2 kinases, mst1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (tlr) 2-interleukin receptor-1 ass ...201627883091
utility of endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing non-specific inflammatory intrathorcacic lymphadenitis.endobronchial ultrasound-guided transbronchial needle aspiration (ebus-tbna) has emerged as a minimally invasive technique for diagnosing intrathoracic malignancies and some benignancies; however, there are no data available on the utility of ebus-tbna for the diagnosis of non-specific inflammatory intrathoracic lymphadenitis.201627882677
antioxidant and antimutagenic metabolites in animals with opposite sensitivity to tuberculosis mycobacteria and mutagenic xenobiotics.different sensitivity of guinea pigs and rats to mycobacterium tuberculosis and membranotropic mutagenic xenobiotics is associated with differences in the metabolism of amino acid precursors of phospholipids. in turn, specific features of phospholipid metabolism are determined by differences in the level of sulfur-containing regulatory metabolites (methionine, taurine, and glutathione) in tissues. taurine and methionine increase organism's resistance to mycobacterium tuberculosis (typical of rat ...201627878723
evaluation of the efficacy of myco/f lytic system, mgit960 system and lowenstein-jensen medium for recovery of mycobacterium tuberculosis from sterile body fluids.the diagnosis of extrapulmonary tuberculosis (eptb) is challenging due to non-specific symptoms, invasive approach for specimen collection and most importantly, the paucibacillary status. the objective of this assay was to evaluate the efficacy of myco/f lytic system, bactec mycobacteria growth indicator tube (mgit) 960 system and lowenstein-jensen (l-j) medium for recovery of bacilli from sterile body fluids. 214 specimens (114 pleural fluid and 100 pus) from clinically diagnosed eptb patients ...201627876877
evaluation of genexpert mtb/rif for detection of mycobacterium tuberculosis complex and rpo b gene in respiratory and non-respiratory clinical specimens at a tertiary care teaching hospital in saudi arabia.to assess the performance of xpert mtb/rif, an automated molecular test for mycobacterium tuberculosis (mtb) and resistance to rifampin (rif), against smear microscopy and culture method for diagnosis of mtb infection. methods: this is a retrospective analysis of 103 respiratory and 137 non-respiratory patient specimens suspected of tuberculosis at king khalid university hospital, riyadh, kingdom of saudi arabia performed between april 2014 and march 2015. each sample underwent smear microscopy, ...201627874159
primary mycobacterium tuberculosis infection over insulin injection site. 201627873753
biochemical characterization of pe_pgrs61 family protein of mycobacterium tuberculosis h37rv reveals the binding ability to fibronectin.the periodic binding of protein expressed by mycobacterium tuberculosis h37rv with the host cell receptor molecules i.e. fibronectin (fn) is gaining significance because of its adhesive properties. the genome sequencing of m. tuberculosis h37rv revealed that the proline-glutamic (pe) proteins contain polymorphic gc-rich repetitive sequences (pgrs) which have clinical importance in pathogenesis events when the host encounters m. tuberculosis h37rv. the functional parts of pe_pgrs family proteins, ...201627872707
identification of sp110 in horse (equus caballus): isolation of novel splice variants and evidence of activation effects on macrophages.sp110 has previously shown to be a genetic determinant of host resistance to the intracellular pathogen infection in mouse and human. however, its relevant biological information in large non-primate animals still remains unknown. here we report the novel discovery and characterization of three transcript variants of horse sp110. the transcript variant 1 (tv1) of horse sp110 with the longest open reading frame has four domains (sp100, sand, phd and bromo domain). tv2 and tv3 share the same n-ter ...201627865405
formulation studies of inha inhibitors and combination therapy to improve efficacy against mycobacterium tuberculosis.previously, structure-based drug design was used to develop substituted diphenyl ethers with potency against the mycobacterium tuberculosis (mtb) enoyl-acp reductase (inha), however, the highly lipophilic centroid compound, sb-pt004, lacked sufficient efficacy in the acute murine mtb infection model. a next generation series of compounds were designed with improved specificity, potency against inha, and reduced cytotoxicity in vitro, but these compounds also had limited solubility. accordingly, ...201627865404
propidium monoazide and xpert mtb/rif to quantify mycobacterium tuberculosis cells.propidium monoazide (pma) penetrates non-viable cells with compromised membranes. pma has been proposed to improve the specificity of xpert mtb/rif (xpert) for the detection of viable mycobacterium tuberculosis. this study assessed the effect of pma on xpert cycle thresholds (ct) of m. tuberculosis made non-viable under antibiotic pressure. in vitro, we measured the difference between ct with and without pma (δct) in liquid cultures treated with one of six anti-tuberculosis drugs (isoniazid, rif ...201627865403
some proteins of m. tuberculosis that localise to the nucleus of thp-1-derived macrophages.host-pathogen dialectics in tuberculosis (tb) via dna-protein interactions are emerging. we investigated whether proteins produced by mycobacterium tuberculosis (mtb) could translocate to the host nucleus. using lysates of nuclei purified from mtb-infected thp-1-derived macrophages, we identified at least 15 proteins of mtb-origin by electrophoretic and chromatographic separation and mass spectrometry. western blotting confirmed time-dependent accumulation of mtb ef-tu, groel, groes and mtra in ...201627865402
new mycobacterium tuberculosis lam sublineage with geographical specificity for the old world revealed by phylogenetical and bayesian analyses.we recently showed that the mycobacterium tuberculosis sublineage lam9 could be subdivided as two distinct subpopulations - each reflecting its unique biogeographical structure and evolutionary history. we subsequently attempted to verify if this genetic structuration could be traced in an enlarged global sample. for this purpose, we analyzed global evolutionary relationships of lam strains in a large dataset (n = 1923 isolates from 35 countries worldwide) with concomitant spoligotyping and miru ...201627865400
transmission of multi-drug resistant tuberculosis in mongolia is driven by beijing strains of mycobacterium tuberculosis resistant to all first-line drugs.mongolia has high and rising rates of multi-drug resistant tuberculosis (mdr-tb). spatio-temporal and programmatic evidence suggests a major contribution from mdr-tb transmission, but genotypic evidence has not been assessed.201627865397
innovative tuberculosis symposium held during cuba salud 2015.the fourth tuberculosis (tb) symposium, held during the cuba salud 2015 international convention, highlighted advancements in research on tb and mycobacterium tuberculosis (mtb) by interdisciplinary teams from academic and federal institutions in cuba, colombia, mexico, and the dominican republic. delegates focused on the targets presented in the world health organization end tb strategy for 2016-2035 and elaborated on four primary themes: 1) attention to vulnerable populations such as immunocom ...201627865395
recent developments in genomics, bioinformatics and drug discovery to combat emerging drug-resistant tuberculosis.emergence of drug-resistant tuberculosis (dr-tb) is a big challenge in tb control. the delay in diagnosis of dr-tb leads to its increased transmission, and therefore prevalence. recent developments in genomics have enabled whole genome sequencing (wgs) of mycobacterium tuberculosis (m. tuberculosis) from 3-day-old liquid culture and directly from uncultured sputa, while new bioinformatics tools facilitate to determine dr mutations rapidly from the resulting sequences. the present drug discovery ...201627865394
selective reduction of ifn-γ single positive mycobacteria-specific cd4+ t cells in hiv-1 infected individuals with latent tuberculosis infection.hiv-1 is recognized to increase the risk for tuberculosis even before cd4+ t cell deficiency is profound. to better understand how hiv-1 alters immunity to latent tuberculosis, we compared the magnitude and functional profile of mycobacteria-specific cd4+ t cells between hiv-uninfected and hiv-infected individuals, using flow cytometry. in hiv-1 infection, ifn-γ single positive mycobacteria-specific cd4+ t cells were decreased, while the frequency of polyfunctional cells (ifn-γ+il-2+tnf-α+) rema ...201627865393
mycobacterium indicus pranii (mip) mediated host protective intracellular mechanisms against tuberculosis infection: involvement of tlr-4 mediated signaling.mycobacterium tuberculosis infection inflicts the disease tuberculosis (tb), which is fatal if left untreated. during m. tuberculosis infection, the pathogen modulates tlr-4 receptor down-stream signaling, indicating the possible involvement of tlr-4 in the regulation of the host immune response. mycobacterium indicus pranii (mip) possesses immuno-modulatory properties which induces the pro-inflammatory responses via induction of tlr-4-mediated signaling. here, we observed the immunomodulatory p ...201627865392
alternative bcg delivery strategies improve protection against mycobacterium tuberculosis in non-human primates: protection associated with mycobacterial antigen-specific cd4 effector memory t-cell populations.intradermal (id) bcg injection provides incomplete protection against tb in humans and experimental models. alternative bcg vaccination strategies may improve protection in model species, including rhesus macaques. this study compares the immunogenicity and efficacy of bcg administered by id and intravenous (iv) injection, or as an intratracheal mucosal boost (id + it), against aerosol challenge with mycobacterium tuberculosis erdman strain. disease pathology was significantly reduced, and survi ...201627865390
quick and cheap miru-vntr typing of mycobacterium tuberculosis species complex using duplex pcr.while minisatellites are usually typed using capillary sequencers or qiaplex systems in developed countries, many low-resource regions cannot afford it. we propose an optimized agarose gel electrophoresis method to genotype mycobacterium tuberculosis species complex minisatellites in their standardized format (24 miru-vntr). it is based on duplex pcrs combining vntr loci harboring distinct amplicon sizes whatever the repetition number of each locus. this method performs well both on dna extracts ...201627865388
microrna expression signatures in lungs of mice infected with mycobacterium tuberculosis.tuberculosis (tb) is a major public health concern worldwide; however the factors that account for resistance or susceptibility to disease are not completely understood. although some studies suggest that the differential expression of mirnas in peripheral blood of tb patients could be useful as biomarkers of active disease, their involvement during the inflammatory process in lungs of infected individuals is unknown. here, we evaluated the global expression of mirnas in the lungs of mice experi ...201627865387
the in vitro mechanisms of isoniazid and ethionamide resistance poorly reflect those in vivo in mycobacterium tuberculosis. 201627865384
analytical and clinical performance characteristics of the abbott realtime mtb rif/inh resistance, an assay for the detection of rifampicin and isoniazid resistant mycobacterium tuberculosis in pulmonary specimens.clinical management of drug-resistant tuberculosis patients continues to present significant challenges to global health. to tackle these challenges, the abbott realtime mtb rif/inh resistance assay was developed to accelerate the diagnosis of rifampicin and/or isoniazid resistant tuberculosis to within a day. this article summarizes the performance of the abbott realtime mtb rif/inh resistance assay; including reliability, analytical sensitivity, and clinical sensitivity/specificity as compared ...201627865383
development of immune-biomarkers of pulmonary tuberculosis in a rabbit model.tuberculosis (tb) causes extensive morbidity and mortality worldwide with approximately 10 million new cases of active disease emerging mostly from a pool of two billion individuals latently infected with mycobacterium tuberculosis (m. tb) every year. the underlying host immune responses that drive m. tb infection to active disease or latency are not well understood. we propose that identification and characterization of host immune biomarkers will be helpful to better understand the mechanisms ...201627865378
a study on knowledge and awareness about tuberculosis in senior school children in bangalore, india.tuberculosis (tb) is an infectious disease caused by mycobacterium tuberculosis (m. tuberculosis), commonly affecting the lungs. all health care professionals including the pharmacists provide a valuable public health role in promoting community awareness of tb particularly in reducing stigma attached to tb. thus, creating awareness at a community level could play a vital role in control and prevention of tb.201627865242
role of real-time pcr for detection of tuberculosis and drug resistance directly from clinical samples.only a few studies done earlier in india reveal the utility of real-time pcr in detecting drug resistance in cases of pulmonary tuberculosis.201627865235
rapid detection of extensively drug-resistant (xdr-tb) strains from multidrug-resistant tuberculosis (mdr-tb) cases isolated from smear-negative pulmonary samples in an intermediate reference laboratory in india.direct sputum smear microscopy is commonly used for diagnosing tuberculosis (tb). the objectives of the study were first, to determine the recovery of mycobacterium tuberculosis in smear-negative sputum samples through liquid culture (using mgit 960) and solid culture (using lj slant) and second, to screen multidrug-resistant isolates through line probe assay and further third, to identify xdr isolates through mgit second-line dst from these positive mdr cultures in delhi region.201627865234
endometrial tuberculosis simulating an ovarian cancer: a case report.female genital tuberculosis remains a major health problem in developing countries and is an important cause of infertility. as symptoms, laboratory data and physical findings are non-specific, its diagnosis can be difficult. we describe a case of a 39-year-old woman suffering from peri-umbilical pain and increased abdominal size for one year, anorexia, asthenia, weight loss, occasionally dysuria and dyspareunia, and four months amenorrhea. laboratory data revealed cancer antigen 125 (ca-125) le ...201627865222
discovery of cofactor-specific, bactericidal mycobacterium tuberculosis inha inhibitors using dna-encoded library technology.millions of individuals are infected with and die from tuberculosis (tb) each year, and multidrug-resistant (mdr) strains of tb are increasingly prevalent. as such, there is an urgent need to identify novel drugs to treat tb infections. current frontline therapies include the drug isoniazid, which inhibits the essential nadh-dependent enoyl-acyl-carrier protein (acp) reductase, inha. to inhibit inha, isoniazid must be activated by the catalase-peroxidase katg. isoniazid resistance is linked prim ...201627864515
armed conflict and population displacement as drivers of the evolution and dispersal of mycobacterium tuberculosis.the "beijing" mycobacterium tuberculosis (mtb) lineage 2 (l2) is spreading globally and has been associated with accelerated disease progression and increased antibiotic resistance. here we performed a phylodynamic reconstruction of one of the l2 sublineages, the central asian clade (cac), which has recently spread to western europe. we find that recent historical events have contributed to the evolution and dispersal of the cac. our timing estimates indicate that the clade was likely introduced ...201627872285
drug resistance and population structure of m.tuberculosis isolates from prisons and communities in ethiopia.the population structure and drug resistance pattern of mycobacterium tuberculosis complex (mtbc) isolates in ethiopian prisons and some communities is still unknown.201627871250
genomic epidemiology of lineage 4 mycobacterium tuberculosis subpopulations in new york city and new jersey, 1999-2009.whole genome sequencing (wgs) has rapidly become an important research tool in tuberculosis epidemiology and is likely to replace many existing methods in public health microbiology in the near future. wgs-based methods may be particularly useful in areas with less diverse mycobacterium tuberculosis populations, such as new york city, where conventional genotyping is often uninformative and field epidemiology often difficult. this study applies four candidate strategies for wgs-based identificat ...201627871225
diagnostic challenges in a patient with myocardial tuberculoma: a case report.tuberculosis can affect any organ of the body, including the heart.201627871010
the perilipin-like ppe15 protein in mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy-inducing conditions. 201627870476
bacterial pathogens versus autophagy: implications for therapeutic interventions.research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. in this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. instead, studies in animal models have revealed ...201627866924
discovery of novel n-phenyl 1,4-dihydropyridines with a dual mode of antimycobacterial activity.there is an urgent need for novel drugs for the treatment of tuberculosis (tb) due to the increasing prevalence of antibiotic resistance among mycobacterium tuberculosis (mtb) strains against first-line and second-line therapeutics. we developed novel n-phenyl 1,4-dihydropyridines as potential antituberculotic agents. the observed activity depends on the substitution patterns of the aromatic residues. n-unsubstituted 1,4-dihydropyridines are known inhibitors of the cancer-relevant transmembrane ...201627866817
tuberculosis presenting as a 'swollen calf'.we report the case of an 83-year-old man who presented with swelling of his left lower leg. subsequent investigations revealed that the swelling was due to a mycobacterium tuberculosis abscess in the tibialis anterior muscle.201627881584
identification of hla-drb1*09:01-restricted mycobacterium tuberculosis cd4(+) t-cell epitopes.cd4(+) t cells play an essential role in protection against mycobacterium tuberculosis (mtb) infection. we identified three hla-drb1*09:01-restricted cd4(+) t-cell epitopes derived from the dominant secreted mtb antigens 38 kda (rv3804c) and ag85a (rv0934). the antigens were screened for epitopes by in silico prediction programs and analysis of ifn-γ induction in the peripheral blood mononuclear cells (pbmcs) from tb patients. in response to three of the high-affinity predicted epitopes derived ...201627861807
disseminated mycobacterium tuberculosis following renal transplant with alemtuzumab induction.mycobacterium tuberculosis presents unique challenges in the peritransplant period. here, we describe a case of disseminated tuberculosis following renal transplantation with alemtuzumab induction immunosuppression in a patient with remotely treated pulmonary tuberculosis and ongoing risk factors for re-infection. we also review the available literature regarding the prevalence of tuberculosis infection following solid organ transplant and management of high-risk patients, including the role for ...201627852682
type i ifn inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of ifn-γ signaling.tuberculosis causes ∼1.5 million deaths every year, thus remaining a leading cause of death from infectious diseases in the world. a growing body of evidence demonstrates that type i ifn plays a detrimental role in tuberculosis pathogenesis, likely by interfering with ifn-γ-dependent immunity. in this article, we reveal a novel mechanism by which type i ifn may confer protection against mycobacterium tuberculosis infection in the absence of ifn-γ signaling. we show that production of type i ifn ...201627849167
the impact of mass gathering on the burden of multidrug resistant mycobacterium tuberculosis in al-madinah al-monawarah region, saudi arabia.the pattern of mycobacterium tuberculosis susceptibility to first line drugs and multidrug resistance in al-madinah al-munawarah, a seasonally overcrowded are during hajj and omrah, is not well studied.201627848902
synthesis of ramariolide natural products and discovery of their targets in mycobacteria.ramariolides a-d are natural products with antibacterial activity. to exploit their cellular mechanism, we here devise the first total synthesis and prepare a photoprobe for target identification. antibacterial testing against several pathogenic strains including mycobacterium tuberculosis revealed the highest potency for ramariolide a. chemical proteomics unraveled binding to essential proteins for amino acid anabolism.201627847948
corrigendum to "correlating rrs and eis promoter mutations in clinical isolates of mycobacterium tuberculosis with phenotypic susceptibility levels to the second-line injectables" [int. j. mycobacteriol. 5(1) 2016 1-6]. 201627847030
expression profile of mce4 operon of mycobacterium tuberculosis following environmental stress.the mce4 operon is one of the four mce operons with eight genes (yrbe4a, yrbe4b, mce4a, mce4b, mce4c, mce4d, mce4e and mce4f) of mycobacterium tuberculosis. it expresses in the later phase of infection and imports cholesterol for long term survival of the bacilli. to cause latent infection, m. tuberculosis undergoes metabolic reprogramming of its genes to survive in the hostile environment like low availability of oxygen and nutrition depletion inside the host.201627847019
more than half of presumptive multidrug-resistant cases referred to a tuberculosis referral laboratory in the tigray region of ethiopia are multidrug resistant.generating epidemiological data on multidrug-resistant tuberculosis (mdr-tb) is essential to assess the magnitude and trends of anti-tb drug resistance. this study determined the prevalence of mdr-tb among presumptive mdr cases referred to a tb referral laboratory in the tigray region of ethiopia.201627847018
molecular detection of fluoroquinolone resistance-associated gyra mutations in ofloxacin-resistant clinical isolates of mycobacterium tuberculosis from iran and belarus.detection of mutations in the quinolone resistance-determining region (qrdr) of the gyra gene could determine resistance to fluoroquinolone antituberculosis drugs. the aim of this study was to detect mutations in qrdrs.201627847014
tuberculosis in sardinia: an investigation into the relationship between natives and immigrants.tuberculosis (tb) has had a recrudescence in the last few decades in italy as a result of many factors, among which migration from countries where tb is endemic is one of them. in sardinia, a major island of italy, there was no knowledge of the mechanisms of transmission of tb in the immigrant subpopulation and the impact it may have on the native subpopulation and on the community as a whole. therefore, a molecular epidemiological study was carried out to get a clearer picture of the number and ...201627847011
nontuberculous mycobacteria in fistula-in-ano: a new finding and its implications.nontuberculous mycobacteria (ntm) are not known to be associated with fistula-in-ano. ntm was detected in three fistula-in-ano patients in our series. in this study, related data was reviewed to find the mycobacterial disease in patients in our database.201627847010
adequacy of examining one sputum specimen in tuberculosis drug resistance surveys.collection of one spot and one morning sputum specimen is recommended for tuberculosis (tb) drug resistance surveys. this was a retrospective analysis of mycobacterium tuberculosis cultures isolated from two spot sputum specimens collected from smear positive tb patients in a tb drug resistance survey. it was conducted to understand the value of a second specimen.201627847007
epidemiology of multidrug-resistant, extensively drug resistant, and totally drug resistant tuberculosis in middle east countries.the 2015 represent the deadline for the global tuberculosis (tb) targets set through the millennium development goals (mdg). from 2016 and onward, new goals were set to end the global tb epidemic via implementing new campaign entitled "the end tb strategy". the major hurdle to end tb epidemic in several parts of the world is the emergence and spread of drug resistant mycobacterium tuberculosis (mtb) strains. the better understanding of the actual global burden of drug resistant tuberculosis woul ...201627847005
population-based drug resistance surveillance of multidrug-resistant tuberculosis in taiwan, 2007-2014.to determine the extent of drug resistance in multidrug-resistant tuberculosis (mdr-tb) cases, we conducted a retrospective, population-based analysis using drug susceptibility testing (dst) results of mdr mycobacterium tuberculosis complex isolates obtained from 2007-2014 in taiwan.201627846235
roles of endoplasmic reticulum stress-mediated apoptosis in m1-polarized macrophages during mycobacterial infections.alteration of macrophage function has an important regulatory impact on the survival of intracellular mycobacteria. we found that macrophages infected with attenuated mycobacterium tuberculosis (mtb) strain h37ra had elevated expression of m1-related molecules, whereas the m2 phenotype was dominant in macrophages infected with virulent mtb h37rv. further, the tlr signalling pathway played an important role in modulating macrophage polarization against mtb infection. interestingly, endoplasmic re ...201627845414
platelet-lymphocyte ratios: a potential marker for pulmonary tuberculosis diagnosis in copd patients.in recent decades, morbidity and mortality have been found to be significantly increased in patients with chronic obstructive pulmonary disease (copd) complicated with pulmonary tuberculosis (ptb). platelet-lymphocyte ratio (plr) is an indicator for inflammatory diseases. this study aims to investigate whether plr could act as a potential marker for patients with copd complicated with ptb.201627843310
pseudotumoral form of soft tissue tuberculosis of the hand: six cases.musculoskeletal involvement is not uncommon in extra-pulmonary tuberculosis, but the localization in the soft tissue of the hand is very rare. diagnosis is much more difficult because of the atypical location and non-specific symptoms. we report 6 cases of pseudotumoral form of soft tissue tuberculosis of the hand treated in our department during the past 12 years. the mean age of the patients was 51 years with extremes of 44 and 63 years. a marked female predominance was observed (sex ratio = 0 ...201628292140
house of cellulose - a new hideout for drug tolerant mycobacterium tuberculosis.mycobacterium tuberculosis (mtb) causes tuberculosis (tb). the treatment of tb requires administration of multiple drugs for long durations because of the unusual drug tolerance of mtb. the phenotypic drug tolerance of genetically drug-susceptible mtb in humans can be explained by its ability to form biofilms. recent studies from different laboratories suggest that mtb forms biofilms that harbour drug-tolerant bacteria. these findings have created a new area of research in the field of mycobacte ...201628357368
docking-based virtual screening of known drugs against mure of mycobacterium tuberculosis towards repurposing for tb.repurposing has gained momentum globally and become an alternative avenue for drug discovery because of its better success rate, and reduced cost, time and issues related to safety than the conventional drug discovery process. several drugs have already been successfully repurposed for other clinical conditions including drug resistant tuberculosis (dr-tb). though tb can be cured completely with the use of currently available anti-tubercular drugs, emergence of drug resistant strains of mycobact ...201628275291
rpf proteins are the factors of reactivation of the dormant forms of actinobacteria.as the response to unfavorable growth conditions, nonsporulating mycobacteria transform into the dormant state with the concomitant formation of the specialized dormant forms characterized by low metabolic activity and resistance to antibiotics. such dormant cells can be reactivated under the influence of several factors including proteins of rpf (resuscitation promoting factor) family, which possess peptidoglycan hydrolase activity and were considered to belong to the group of the autocrine gro ...201628260493
genomic characterization of mycobacterium tuberculosis lineage 7 and a proposed name: 'aethiops vetus'.lineage 7 of the mycobacterium tuberculosis complex has recently been identified among strains originating from ethiopia. using different dna typing techniques, this study provides additional information on the genetic heterogeneity of five lineage 7 strains collected in the amhara region of ethiopia. it also confirms the phylogenetic positioning of these strains between the ancient lineage 1 and tbd1-deleted, modern lineages 2, 3 and 4 of mycobacterium tuberculosis. four newly identified large ...201628348856
declaring a tuberculosis outbreak over with genomic epidemiology.we report an updated method for inferring the time at which an infectious disease was transmitted between persons from a time-labelled pathogen genome phylogeny. we applied the method to 48 mycobacterium tuberculosis genomes as part of a real-time public health outbreak investigation, demonstrating that although active tuberculosis (tb) cases were diagnosed through 2013, no transmission events took place beyond mid-2012. subsequent cases were the result of progression from latent tb infection to ...201628348853
design, synthesis and anti-tubercular activity of novel 1, 4-dihydropyrine-3, 5-dicarboxamide containing 4(5)-chloro-2-ethyl- 5(4)-imidazolyl moiety.current researches have showed that n3, n5-diaryl-2, 6-dimethyl -1, 4-dihydropyrine-3, 5- dicarboxamide analogues demonstrate notable anti-tubercular activity. in this study, hantzsch condensation was used to design and synthesize new analogues of dihydropyridine (dhp). different diary carboxamides were inserted at positions 3 and 5 of the dhp ring. 4(5)-chloro-2-ethyl-5(4)-imidazolyl moiety was considered at position 4 of the dhp ring. the structures of prepared ligands were characterized using ...201628243275
an in silico model of the effects of vitamin d3 on mycobacterium infected macrophage.mycobacterium tuberculosis is a global health concern, causing over one million deaths a year. alveolar macrophages, as the primary host cell of this intracellular bacterium, play an important role in the course of disease. vitamin d3 is known to have a potent effect on macrophage behavior during infection, modulating the production of pro- and anti-inflammatory cytokines and immune effector molecules. in a vitamin d3 deficient host, the immune systems response to infection is greatly impaired. ...201628268597
identification of potential leads against 4-hydroxytetrahydrodipicolinate synthase from mycobacterium tuberculosis.4-hydroxy-tetrahydrodipicolinate synthase (dhdps) is an important enzyme needed for the biosynthesis of lysine and many more key metabolites in mycobacterium tuberculosis (mtb). inhibition of dhdps is supposed to a promising therapeutic target due to its specific role in sporulation, cross-linking of the peptidiglycan polymers and biosynthesis of amino acids. in this work, a known inhibitor-based similarity search was carried out against a natural products database (super natural ii) towards ide ...201628293071
utility of phenotypic and genotypic testing in the study of mycobacterium tuberculosis resistance to first-line anti-tuberculosis drugs.to determine the utility of molecular techniques in the diagnosis of resistance and the extent of resistance to first-line drugs in our region.201628277228
insights from the analysis of predicted rv0679c protein peptide from mycobacterium tuberculosis with toll like receptors in host.peptides of rv0679c a membrane protein of the cell envelope (16.6 kda) of mycobacterium tuberculosis (m. tb), inhibited entry of live bacilli into epithelial (a549) and macrophage (u937) cell lines in vitro, suggesting a possible role in invasion. receptors associated with rv0679c antigen entry into cell lines were not characterized. we are reporting that rv0679c peptides could bind to toll like receptors (tlrs), the principal class of pathogen recognition receptors on host cells (prr) by dockin ...201628246463
clinical application of interferon-γ release assays for the prevention of tuberculosis in countries with low incidence.despite global efforts to control tuberculosis (tb) the estimated number of people who developed tb worldwide increased to an all-time record of more than 10 million in 2015. the goal of the world health organization (who) to reduce the global incidence of tb to less than 100 cases per million by 2035, cannot be reached unless tb prevention is markedly improved. there is a need for an improved vaccine that better protects individuals who are exposed to mycobacterium tuberculosis from infection a ...201628217762
[clinical and morphological parallels in the validation of surgical treatment of nephrotuberculosi].to study clinical and morphological variants of kidney tuberculosis (ktb), for grounding a tactics of surgical treatment.201628248043
accuracy of a new rapid antigen detection test for pulmonary tuberculosis.tuberculosis (tb) is a major problem in the world. treatment and control of tb needs detection of the mycobacterium tuberculosis (mt) in the proper samples. while smear doesn't have enough sensitivity, culture and pcr are expensive, time consuming and unavailable in many centers. recent development of a rapid tb antigen detection test (prtbk) at pasteur institute of iran could give a simple way for diagnosis of tb in about two hours. in this test the antigen-antibody complex will change color wh ...201628210462
insights into pyrazinamidase and dna gyrase protein structures in resistant and susceptible clinical isolates of mycobacterium tuberculosis.mutations in pnca and gyra genes cause pyrazinamide (pza) and fluroquinolone resistance in mycobacterium tuberculosis (mtb). in the present study, structures of pyrazinamidase (pzase) and dna gyrase proteins were studied in resistant and susceptible clinical isolates of mtb.201628210279
sputum collection and disposal perceptions and practices among pulmonary tuberculosis patients from northern india.even a single case of pulmonary tuberculosis (tb) can infect many others. hence, to ensure better control of the disease, it is imperative that all patients dispose their sputum safely. outcomes of this study would highlight the gaps need to be bridged in order to curtail transmission of tb.201628208887
mass spectral determination of phosphopantetheinylation specificity for carrier proteins in mycobacterium tuberculosis.phosphopantetheinyl transferases (pptases) are key elements in the modular syntheses performed by multienzyme systems such as polyketide synthases. pptases transfer phosphopantetheine derivatives from coenzyme a to carrier proteins (cps), thus orchestrating substrate supply. we describe an efficient mass spectrometry-based protocol for determining cp specificity for a particular pptase in organisms possessing several candidate pptases. we show that the cps mbtl and ppsc, both involved in synthes ...201628203522
primary ethambutol resistance among iranian pulmonary tuberculosis patients: a systematic review.ethambutol (emb) is an anti-mycobacterial agent that is most commonly used in combination with other anti-tuberculosis (tb) drugs in the treatment of tb. studies have shown that primary resistance rates of mycobacterium tuberculosis to emb vary widely, that is, from 1% to as high as 14%. in this study, we aimed to determine the exact prevalence of primary emb resistance among pulmonary tb cases.201628149517
molecular typing methods used in studies of mycobacterium tuberculosis in iran: a systematic review.molecular typing methods are important and useful tools to assess the transmission, diversity of strains and differentiation between new infections and relapses which can effectively help in controlling infections. the aim of this study was to evaluate the molecular typing methods which have been used in iran. by evaluating the results and discriminatory power of each method, we can assign appropriate weight to each technique and ultimately offer a common strategy for future epidemiological stud ...201628149495
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