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pe_pgrs33 contributes to mycobacterium tuberculosis entry in macrophages through interaction with tlr2.pe_pgrs represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an n-terminal pe domain followed by a large gly-ala repeat-rich c-terminal domain. despite the abundance of pe_pgrs-coding genes in the mycobacterium tuberculosis (mtb) genome their role and function in the biology and pathogenesis still remains elusive. in this study, we generated and characterized an mtb h37rv mutant (mtbδ33) in which the structural gene of pe_pgrs33, a prototypic ...201626978522
implementation of a collaborative series of classroom-based undergraduate research experiences spanning chemical biology, biochemistry, and neurobiology.classroom undergraduate research experiences (cures) provide students access to the measurable benefits of undergraduate research experiences (ures). herein, we describe the implementation and assessment of a novel model for cohesive cures focused on central research themes involving faculty research collaboration across departments. specifically, we implemented three collaborative cures spanning chemical biology, biochemistry, and neurobiology that incorporated faculty members' research interes ...201627810870
crystal structures of mycobacterium tuberculosis hspat and arat reveal structural basis of their distinct substrate specificities.aminotransferases of subfamily iβ, which include histidinol phosphate aminotransferases (hspats) and aromatic amino acid aminotransferases (arats), are structurally similar but possess distinct substrate specificities. this study, encompassing structural and biochemical characterisation of hspat and arat from mycobacterium tuberculosis demonstrates that the residues lining the substrate binding pocket and n-terminal lid are the primary determinants of their substrate specificities. in mhspat, hy ...201626738801
the toxin-antitoxin system dartg catalyzes reversible adp-ribosylation of dna.the discovery and study of toxin-antitoxin (ta) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell death. here we identify and characterize a ta system found in various bacteria, including the global pathogen mycobacterium tuberculosis. the toxin of the system (dart) is a domain of unknown function ...201627939941
imaging the nadh:nad(+) homeostasis for understanding the metabolic response of mycobacterium to physiologically relevant stresses.the nadh:nad(+) ratio is the primary indicator of the metabolic state of bacteria. nad(h) homeostasis is critical for mycobacterium tuberculosis (mtb) survival and is thus considered an important drug target, but the spatio-temporal measurements of nad(h) remain a challenge. genetically encoded fluorescent biosensors of the nadh:nad(+) ratios were recently described, paving the way for investigations of the metabolic state of pathogens during infection. here we have adapted the genetically encod ...201627878107
mycobacterium tuberculosis transcription machinery: ready to respond to host attacks.regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. for pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. inappropriate responses have consequences; h ...201626883824
inhibition of bacterial rnase p rna by phenothiazine derivatives.there is a need to identify novel scaffolds and targets to develop new antibiotics. methylene blue is a phenothiazine derivative, and it has been shown to possess anti-malarial and anti-trypanosomal activities. here, we show that different phenothiazine derivatives and pyronine g inhibited the activities of three structurally different bacterial rnase p rnas (rprs), including that from mycobacterium tuberculosis, with ki values in the lower μm range. interestingly, three antipsychotic phenothiaz ...201627618117
reconstitution of protein translation of mycobacterium reveals functional conservation and divergence with the gram-negative bacterium escherichia coli.protein translation is essential for all bacteria pathogens. it has also been a major focus of structural and functional studies and an important target of antibiotics. here we report our attempts to biochemically reconstitute mycobacterial protein translation in vitro from purified components. this mycobacterial translation system consists of individually purified recombinant translation factors from mycobacterium tuberculosis (m. tuberculosis), purified trnas and ribosomes from mycobacterium s ...201627564552
a mutation in the 16s rrna decoding region attenuates the virulence of mycobacterium tuberculosis.mycobacterium tuberculosis contains a single rrna operon that encodes targets for antituberculosis agents, including kanamycin. to date, only four mutations in the kanamycin binding sites of 16s rrna have been reported in kanamycin-resistant clinical isolates. we hypothesized that another mutation(s) in the region may dramatically decrease m. tuberculosis viability and virulence. here, we describe an rrna mutation, u1406a, which was generated in vitro and confers resistance to kanamycin while hi ...201627245411
genomic and transcriptomic analysis of the streptomycin-dependent mycobacterium tuberculosis strain 18b.the ability of mycobacterium tuberculosis to establish a latent infection (ltbi) in humans confounds the treatment of tuberculosis. consequently, there is a need to discover new therapeutic agents that can kill m. tuberculosis both during active disease and ltbi. the streptomycin-dependent strain of m. tuberculosis, 18b, provides a useful tool for this purpose since upon removal of streptomycin (str) it enters a non-replicating state that mimics latency both in vitro and in animal models.201626944551
structural similarities and differences between two functionally distinct seca proteins, mycobacterium tuberculosis seca1 and seca2.while seca is the atpase component of the major bacterial secretory (sec) system, mycobacteria and some gram-positive pathogens have a second paralog, seca2. in bacteria with two seca paralogs, each seca is functionally distinct, and they cannot compensate for one another. compared to seca1, seca2 exports a distinct and smaller set of substrates, some of which have roles in virulence. in the mycobacterial system, some seca2-dependent substrates lack a signal peptide, while others contain a signa ...201626668263
discovery of novel haloalkane dehalogenase inhibitors.haloalkane dehalogenases (hlds) have recently been discovered in a number of bacteria, including symbionts and pathogens of both plants and humans. however, the biological roles of hlds in these organisms are unclear. the development of efficient hld inhibitors serving as molecular probes to explore their function would represent an important step toward a better understanding of these interesting enzymes. here we report the identification of inhibitors for this enzyme family using two different ...201626773086
comparison of sample preparation methods used for the next-generation sequencing of mycobacterium tuberculosis.the advent and widespread application of next-generation sequencing (ngs) technologies to the study of microbial genomes has led to a substantial increase in the number of studies in which whole genome sequencing (wgs) is applied to the analysis of microbial genomic epidemiology. however, microorganisms such as mycobacterium tuberculosis (mtb) present unique problems for sequencing and downstream analysis based on their unique physiology and the composition of their genomes. in this study, we co ...201626849565
the preprotein translocase yidc controls respiratory metabolism in mycobacterium tuberculosis.the yidc-oxa1-alb3 preprotein translocases play a vital role in membrane insertion of proteins in eukaryotes and bacteria. in a recent study we observed that rv3921c, which encodes putative yidc translocase in mycobacterium tuberculosis (mtb), is essential for in vitro growth of bacteria. however, the exact function of this particular protein remains to identify in mycobacterial pathogens. by performing a systematic study here we show that yidc of mtb is an envelope protein, which is required fo ...201627166092
a rheostat mechanism governs the bifurcation of carbon flux in mycobacteria.fatty acid metabolism is an important feature of the pathogenicity of mycobacterium tuberculosis during infection. consumption of fatty acids requires regulation of carbon flux bifurcation between the oxidative tca cycle and the glyoxylate shunt. in escherichia coli, flux bifurcation is regulated by phosphorylation-mediated inhibition of isocitrate dehydrogenase (icd), a paradigmatic example of post-translational mechanisms governing metabolic fluxes. here, we demonstrate that, in contrast to e. ...201627555519
the duf59 containing protein suft is involved in the maturation of iron-sulfur (fes) proteins during conditions of high fes cofactor demand in staphylococcus aureus.proteins containing duf59 domains have roles in iron-sulfur (fes) cluster assembly and are widespread throughout eukarya, bacteria, and archaea. however, the function(s) of this domain is unknown. staphylococcus aureus suft is composed solely of a duf59 domain. we noted that suft is often co-localized with sufbc, which encode for the suf fes cluster biosynthetic machinery. phylogenetic analyses indicated that suft was recruited to the suf operon, suggesting a role for suft in fes cluster assembl ...201627517714
mycobacterium tuberculosis devr/dosr dormancy regulator activation mechanism: dispensability of phosphorylation, cooperativity and essentiality of α10 helix.devr/dosr is a well-characterized regulator in mycobacterium tuberculosis which is implicated in various processes ranging from dormancy/persistence to drug tolerance. devr induces the expression of an ~48-gene dormancy regulon in response to gaseous stresses, including hypoxia. strains of the beijing lineage constitutively express this regulon, which may confer upon them a significant advantage, since they would be 'pre-adapted' to the environmental stresses that predominate during infection. a ...201627490491
cell-envelope remodeling as a determinant of phenotypic antibacterial tolerance in mycobacterium tuberculosis.the mechanisms that lead to phenotypic antibacterial tolerance in bacteria remain poorly understood. we investigate whether changes in nacl concentration toward physiologically higher values affect antibacterial efficacy against mycobacterium tuberculosis (mtb), the causal agent of human tuberculosis. indeed, multiclass phenotypic antibacterial tolerance is observed during mtb growth in physiologic saline. this includes changes in sensitivity to ethionamide, ethambutol, d-cycloserine, several am ...201627231718
the most common detected bacteria in sputum of patients with community acquired pneumonia (cap) treated in hospital.community acquired pneumonia (cap) is the most common infective pulmonary disease.201627994296
the ubiquitin ligase trim27 functions as a host restriction factor antagonized by mycobacterium tuberculosis ptpa during mycobacterial infection.macrophage-mediated innate immune responses play crucial roles in host defense against pathogens. recent years have seen an explosion of host proteins that act as restriction factors blocking viral replication in infected cells. however, the essential factors restricting mycobacterium tuberculosis (mtb) and their regulatory roles during mycobacterial infection remain largely unknown. we previously reported that mtb tyrosine phosphatase ptpa, a secreted effector protein required for intracellular ...201627698396
the proneurotrophin receptor sortilin is required for mycobacterium tuberculosis control by macrophages.sorting of luminal and membrane proteins into phagosomes is critical for the immune function of this organelle. however, little is known about the mechanisms that contribute to the spatiotemporal regulation of this process. here, we investigated the role of the proneurotrophin receptor sortilin during phagosome maturation and mycobacterial killing. we show that this receptor is acquired by mycobacteria-containing phagosomes via interactions with the adaptor proteins ap-1 and ggas. interestingly, ...201627389464
identification of a transcription factor that regulates host cell exit and virulence of mycobacterium tuberculosis.the interaction of mycobacterium tuberculosis (mtb) with host cell death signaling pathways is characterized by an initial anti-apoptotic phase followed by a pro-necrotic phase to allow for host cell exit of the bacteria. the bacterial modulators regulating necrosis induction are poorly understood. here we describe the identification of a transcriptional repressor, rv3167c responsible for regulating the escape of mtb from the phagosome. increased cytosolic localization of mtbδrv3167c was accompa ...201627191591
rab gtpases and the autophagy pathway: bacterial targets for a suitable biogenesis and trafficking of their own vacuoles.autophagy is an intracellular process that comprises degradation of damaged organelles, protein aggregates and intracellular pathogens, having an important role in controlling the fate of invading microorganisms. intracellular pathogens are internalized by professional and non-professional phagocytes, localizing in compartments called phagosomes. to degrade the internalized microorganism, the microbial phagosome matures by fusion events with early and late endosomal compartments and lysosomes, a ...201627005665
correction for dietrich et al., differential influence of nutrient-starved mycobacterium tuberculosis on adaptive immunity results in progressive tuberculosis disease and pathology. 201626810750
crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from mycobacterium tuberculosis.mycobacterium tuberculosis (mtb) infects one-third of the world's population and in 2013 accounted for 1.5 million deaths. fluoroquinolone antibacterials, which target dna gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. to better explain known differences in fluoroquinolone action, the crystal structures of the wt mtb dna ...201626792525
respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in cape town, south africa.lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. children with symptoms suggestive of pulmonary tuberculosis (ptb) may have tuberculosis, other respiratory tract infections or co-infection with mycobacterium tuberculosis and other pathogens. we aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (np) samples from children with suspected ptb.201627776489
performance of an in-house real-time polymerase chain reaction for identification of mycobacterium tuberculosis isolates in laboratory routine diagnosis from a high burden setting.brazil is one of the high burden countries for tuberculosis, and a rapid diagnosis is essential for effective control of the disease. in the present study, an in-house real-time polymerase chain reaction (pcr) assay targeting the mpt64 gene for identification of mycobacterium tuberculosis complex isolates was evaluated under routine diagnosis conditions in a reference laboratory. from may 2011 to july 2012, 1,520 isolates of mycobacteria were prospectively submitted for phenotypic and/or pra-hsp ...201627598243
antitubercular drugs for an old target: gsk693 as a promising inha direct inhibitor.despite being one of the first antitubercular agents identified, isoniazid (inh) is still the most prescribed drug for prophylaxis and tuberculosis (tb) treatment and, together with rifampicin, the pillars of current chemotherapy. a high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme katg, so the discovery of direct inhibitors (di) of the enoyl-acp reductase (inha) has been pursued by many groups leading to the identification of different enzyme inhib ...201627428438
rv2744c is a pspa ortholog that regulates lipid droplet homeostasis and nonreplicating persistence in mycobacterium tuberculosis.mycobacterium tuberculosis, the causative agent of tuberculosis (tb), remains a significant cause of morbidity and mortality worldwide, despite the availability of a live attenuated vaccine and anti-tb antibiotics. the vast majority of individuals infected with m. tuberculosis develop an asymptomatic latent infection in which the bacterium survives within host-generated granulomatous lesions in a physiologically altered metabolic state of nonreplicating persistence. the granuloma represents an a ...201627002134
chaperone addiction of toxin-antitoxin systems.bacterial toxin-antitoxin (ta) systems, in which a labile antitoxin binds and inhibits the toxin, can promote adaptation and persistence by modulating bacterial growth in response to stress. some atypical ta systems, known as tripartite toxin-antitoxin-chaperone (tac) modules, include a molecular chaperone that facilitates folding and protects the antitoxin from degradation. here we use a tac module from mycobacterium tuberculosis as a model to investigate the molecular mechanisms by which class ...201627827369
in vitro antimicrobial activities of animal-used quinoxaline 1,4-di-n-oxides against mycobacteria, mycoplasma and fungi.the quinoxaline 1,4-di-n-oxides (qdnos) were known as potent antibacterial agents. for the purpose of evaluating the bioactivity of existing animal-used qdnos drugs against representative pathogenic microorganism, the representative drugs of quinoxalines including cyadox, mequindox, quinocetone and their metabolites were submitted to the in vitro evaluation for antituberculosis, antimycoplasma, antifungal and antiviral activities.201627600955
fermentation, isolation, purification and characterization of an antitubercular antibiotic from streptomyces luridus mtcc 4402.tuberculosis, caused by mycobacterium tuberculosis, continues to be a serious public health problem around the world, and it urges the need for development of new antitubercular drugs. an antibiotic producing strain, streptomyces luridus (mtcc 4402) was earlier isolated from soil by our group. in this work, the phylogenic status was established by 16s rrna gene sequence analysis. the strain was found to be active against clinically resistant strains. the culture was grown in shake flasks in a me ...201628699723
enrichment by hybridisation of long dna fragments for nanopore sequencing.enrichment of dna by hybridisation is an important tool which enables users to gather target-focused next-generation sequence data in an economical fashion. current in-solution methods capture short fragments of around 200-300 nt, potentially missing key structural information such as recombination or translocations often found in viral or bacterial pathogens. the increasing use of long-read third-generation sequencers requires methods and protocols to be adapted for their specific requirements. ...201628785419
an uncommon cause of longitudinally extensive transverse myelitis.considering that currently romania has the highest tuberculosis incidence in europe, the recognition of the infection is an acknowledged health issue. central nervous system tuberculosis accounts for approximately 1% of all cases of tuberculosis. longitudinally extensive transverse myelitis is a contiguous infl ammatory lesion of the spinal cord which involves three or more spinal segments. in tuberculosis, spinal cord involvement is rare and is usually rather due to radiculomyelitis or spinal t ...201628694861
coronins and their role in immunological phenomena.coronins are a large family of proteins occurring in many eukaryotes. in mammals, seven coronin genes have been identified, evidencing that coronins 1 to 6 present classic coronin structure, while coronin 7 is a tandem coronin particle, without a spiral domain, although the best characterised coronin, in terms of both structure and function, is the mammalian coronin 1. it has been proven that they are related to regulation of actin dynamics, e.g. as a result of interaction with the complex of pr ...201628450807
[determination of the rate of growth of mycobacterium tuberculosis and some of its applications]. 201624542595
chest radiographic findings in primary pulmonary tuberculosis: observations from high school outbreaks.to describe the radiographic findings of primary pulmonary tuberculosis (tb) in previously healthy adolescent patients.201621076586
drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis in ibadan, nigeria.information on tb drug resistance profiles and its' associated risk factors are scarce in nigeria despite the large burden of disease in the country. the study was designed to report drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis (tb) in ibadan, nigeria.201628686829
collision of three pandemics: the coexistence of cervical cancer, hiv infection, and prior tuberculosis in the sub-saharan country of botswana.cervical cancer is the leading cause of cancer-related mortality in the developing world, where hiv and mycobacterium tuberculosis (tb) infection are also endemic. hiv infection is independently associated with increased morbidity and mortality among women with cervical cancer. tb is believed to increase the risk of malignancies and could cause chronic inflammation in the gynecologic tract. however, the relationship between cervical cancer and tb in settings hyperendemic for hiv is unknown. we f ...201628717682
a genomics-led approach to deciphering the mechanism of thiotetronate antibiotic biosynthesis.thiolactomycin (tlm) is a thiotetronate antibiotic that selectively targets bacterial fatty acid biosynthesis through inhibition of the β-ketoacyl-acyl carrier protein synthases (kasi/ii) that catalyse chain elongation on the type ii (dissociated) fatty acid synthase. it has proved effective in in vivo infection models of mycobacterium tuberculosis and continues to attract interest as a template for drug discovery. we have used a comparative genomics approach to uncover the (hitherto elusive) bi ...201628791099
[tuberculosis in general practice in belgium : what's new?]tuberculosis is still an important disease in belgium, mainly in big agglomerations. for this reason, knowledge of this entity by a general practitioner is very important. genetic tests able to identify the species of mycobacterium tuberculosis have been developed in recent years, but also identification of resistance to 1st and 2nd line treatment through genetic methods has been developed. the quick availability of results of this tests compared to the standard tests is a big advantage. treatme ...201628525233
surface expression and genetic variants of toll-like receptor 2 in pulmonary tuberculosis patients.innate immunity plays an important role in the host defense against mycobacterium tuberculosis (m. tuberculosis). toll-like receptor-2 (tlr2) is the main receptor and one of central components in initiation of innate immunity against m. tuberculosis. the study aimed to evaluate tlr2 surface expression on peripheral blood monocytes and study its association with variants in tlr2 597t/c single nucleotide polymorphisms (snps) in patients with pulmonary tuberculosis. fifty pulmonary tuberculosis pat ...201628502147
eosinophilic cystitis and cholangitis - systemic disease triggered by mycobacterium tuberculosis?eosinophilic cystitis (ec) is a rare inflammatory disorder of the urinary tract characterized by infiltration of bladder with eosinophils. the cause remains unclear, immunological mechanisms have been implicated in pathogenesis. potential etiological factors include: tumors, allergy, parasitic infections, trauma. the disease may have a variable course, from a mild self-limiting, through common symptoms like: dysuria, hematuria, abdominal pain, tumor, to severe renal failure, with eosinophilic in ...201628478431
clinical research of treating tuberculous respiratory failure by sequential mechanical ventilation.tuberculosis is kind of common chronic infectious disease, of which the pathogenic bacterium is mainly mycobacterium tuberculosis (mtb). one who is suffering severe tuberculosis may be ended with cardio-pulmonary function damage or cardio-pulmonary failure. this disease is of higher risks of complications or even high death rate, which is seriously challenging people's health and life. when a tuberculosis patient is accompanied with respiratory failure, which means the disease has developed into ...201628412688
tuberculous spondylitis of the craniovertebral junction.craniovertebral junction tuberculosis is rare, accounting for 0.3 to 1% of all tuberculous spondylitis cases. mr imaging is the modality of choice to detect bone involvement, abscess formation and subligamentous spreading of the pus, to differentiate from other lesions affecting the craniovertebral junction, and to determine the efficacy of treatment. given the fact that surgical treatment of patients with craniovertebral junction tuberculosis has been associated with a high mortality rate rangi ...201628529850
[genetic recombiniation and protein expression detection of listeria-based tuberculosis vaccine candidates.]genetic construction of tuberculosis vaccine candidates based on listeria(l.) monocytogenes,l.ivanovii,and evaluation their protein expression,in order to provide a novel method for research on tuberculosis controlling.201628598105
tuberculosis and pneumonia in hiv-infected children: an overview.pneumonia remains the most common cause of hospitalization and the most important cause of death in young children. in high human immunodeficiency virus (hiv)-burden settings, hiv-infected children carry a high burden of lower respiratory tract infection from common respiratory viruses, bacteria and mycobacterium tuberculosis. in addition, pneumocystis jirovecii and cytomegalovirus are important opportunistic pathogens. as the vertical transmission risk of hiv decreases and access to antiretrovi ...201628702298
novel vaccination approaches to prevent tuberculosis in children.pediatric tuberculosis (tb) is an underappreciated problem and accounts for 10 % of all tb deaths worldwide. children are highly susceptible to infection with mycobacterium tuberculosis and interrupting tb spread would require the development of effective strategies to control tb transmission in pediatric populations. the current vaccine for tb, m. bovis bacille calmette-guérin (bcg), can afford some level of protection against tb meningitis and severe forms of disseminated tb in children; howev ...201628702297
de novo design of potential reca inhibitors using multi objective optimization.de novo ligand design involves optimization of several ligand properties such as binding affinity, ligand volume, drug likeness, etc. therefore, optimization of these properties independently and simultaneously seems appropriate. in this paper, the ligand design problem is modeled in a multiobjective using archived multiobjective simulated annealing (amosa) as the underlying search algorithm. the multiple objectives considered are the energy components similarity to a known inhibitor and a novel ...201622392725
comparison of the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide tube method with the conventional method and real-time polymerase chain reaction for the detection of rifampicin resistance in mycobacterium tuberculosis.colorimetric methods are cheap, reproducible, and rapid methods of detecting drug resistance in mycobacterium tuberculosis. the mtt (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) method is one such technique that has been established in our laboratory to detect rifampicin resistance. the present study compared the results of the mtt method with those of the proportion method and real-time polymerase chain reaction (rtpcr) in order to establish sensitivity and specificity of mtt. ...201622361766
use of interferon-gamma release assays in a health care worker screening program: experience from a tertiary care centre in the united states.interferon-gamma release assays including the quantiferon-tb gold in-tube test (qft-git [cellestis ltd, australia]) may be used in place of the tuberculin skin test (tst) in surveillance programs for mycobacterium tuberculosis infection control. however, data on performance and practicality of the qft-git in such programs for health care workers (hcws) are limited.201622536576
mycobacterium tuberculosis manlam inhibits t-cell-receptor signaling by interference with zap-70, lck and lat phosphorylation.immune evasion is required for mycobacterium tuberculosis to survive in the face of robust cd4(+) t cell responses. we have shown previously that m. tuberculosis cell wall glycolipids, including mannose capped lipoarabinomannan (manlam), directly inhibit polyclonal murine cd4(+) t cell activation by blocking zap-70 phosphorylation. we extended these studies to antigen-specific murine cd4(+) t cells and primary human t cells and found that manlam inhibited them as well. lck and lat phosphorylatio ...201622507872
rapid diagnosis of mycobacterium tuberculosis infection in children using interferon-gamma release assays (igras).diagnosis of tuberculosis (tb) in children by the tuberculin skin test (tst) poses a diagnostic challenge for physicians due to its low specificity and cross-reactivity with nontuberculous mycobacteria and bacille calmette-guerin (bcg). although interferon-gamma release assays (igras) have been shown as novel tst alternatives for diagnosis of latent tb infection (ltbi) in adults, their effectiveness is less clear in children. the present study examined quantiferon-tb gold (qft-g) responses and i ...201622584190
what every physician should know about rapid diagnosis of mycobacterium tuberculosis infection in children using interferon-gamma release assays. 201622584189
use of tuberculosis genotyping for postoutbreak monitoring.review of routinely collected tuberculosis genotyping results following a known outbreak is a potential mechanism to examine the effectiveness of outbreak control measures.201622635193
primary disseminated extrapulmonary multidrug resistant tuberculosis.disseminated tuberculosis is a common mode of presentation of tuberculosis in patients both with and without hiv/aids in india. however, primary multidrug resistance in disseminated tuberculosis involving only the extrapulmonary sites in an immunocompetent adult is rare. here, we report a case of a 19-year-old man who had disseminated tuberculosis involving left pleura, pericardium, peritoneum and intraabdominal lymph nodes. he was initially taking who category i antituberculous drugs, but was n ...201622885212
calvarial tuberculosis with parenchymal involvement.tuberculosis is an infectious disease caused by the acid-fast bacilli mycobacterium tuberculosis that usually affects the lungs although it may affect any organ. tuberculous osteitis of the cranial bones is an uncommon manifestation of disseminated tuberculosis known as calvarial tuberculosis. cases with parenchymal involvement are infrequent in the literature. we report a case of a patient with multiple osteolytic cranial lesions and a tuberculoma.201623267716
discrimination of single base mismatched oligonucleotides related to the rpob gene of mycobacterium tuberculosis using a surface plasmon resonance biosensor.single base mismatched oligonucleotides related to the rpob gene of mycobacterium tuberculosis, the mutations of which cause drug resistance of the infectious agent, were detected and discriminated using a surface plasmon resonance biosensor system. thiol-modified oligonucleotides of the selected sequence (the probe) and 1-mercapto-6-hexanol were immobilized on a gold sensor surface. hybridization between immobilized probe p2 and perfectly matched target t2 as well as a single base mismatched ta ...201623654350
disseminated tuberculosis presenting as tuberculous peritonitis and sepsis tuberculosa gravissima in a patient with cirrhosis of the liver: a diagnosis of challenge.we report the case of an 81-year-old man diagnosed with liver cirrhosis complicated by spontaneous bacterial peritonitis and septic shock. mycobacterium tuberculosis complex was isolated from the ascites, sputum, and blood culture 1 month after the patient died. clinicians should be aware of the unusual diagnosis of sepsis tuberculosa gravissima presenting with tuberculous peritonitis, which is easily misdiagnosed as spontaneous bacterial peritonitis and gram-negative bacillus sepsis in patients ...201624530253
isolated tuberculous liver abscess in an immunocompetent adult patient: a case report and literature review.tuberculous liver abscess is a rare disease entity even in endemic areas of mycobacterium tuberculosis. it is usually accompanied by pulmonary tuberculosis or enteric tuberculosis. further, an isolated tuberculous liver abscess is extremely rare. the disease is diagnosed by laparotomy or postmortem autopsy in most cases, and some authors adopted a 9-month antituberculosis regimen. we herein report a case of an isolated tuberculous liver abscess that initially manifested as persistent fever and g ...201624231587
current status and future trends in the diagnosis and treatment of drug-susceptible and multidrug-resistant tuberculosis.the global burden of tuberculosis (tb) is still large. the increasing incidence of drug-resistant, multidrug-resistant (mdr) (resistant to at least rifampicin and isoniazid), and extensively drug-resistant (xdr) (additionally resistant to a fluoroquinolone and kanamycin/amikacin/capreomycin) strains of mycobacterium tuberculosis and the association of active disease with human immunodeficiency virus coinfection pose a major threat to tb control efforts. the rapid detection of m. tuberculosis str ...201624216518
[comparison of the data of computed tomography and bacteriological studies in the complicated forms of primary tuberculosis in children and adolescents].to establish the causes of bacterial excretion in complicated primary tuberculosis in children and adolescents, by comparing the data of computed tomography and the results of bacteriological studies.201625702438
[economic impact of the introduction of a technique for early detection of mycobacterium tuberculosis complex in clinical samples in a spanish hospital].tuberculosis (tb) remains an important public health problem worldwide. our objective was to estimate the economic and health care impact of the introduction of an early diagnosis tecnique of tb, the xpert mtb/rif® assay (xpert).201624100779
in silico interaction of methyl isocyanate with immune protein responsible for mycobacterium tuberculosis infection using molecular docking.this article reports in silico analysis of methyl isocyanate (mic) on different key immune proteins against mycobacterium tuberculosis. the analysis shows that mic is released in the bhopal gas tragedy in 1984, which is highly toxic and extremely hazardous to human health. in this study, we have selected immune proteins to perform molecular docking with the help of autodock 4.0. results show that the cd40 ligand and alpha5beta1 integrin have higher inhibition compared to plasminogen activator ur ...201624081639
smelling the diagnosis: a review on the use of scent in diagnosing disease.for centuries, our sense of smell has been used as a diagnostic tool in the practice of medicine, be it for recognising gas gangrene on the battle field or diabetic ketoacidosis in the emergency room. in recent decades, many scent detection studies have been performed with human, animal and electronic noses. the ability of humans to diagnose disease by smelling has only rarely been the subject of quantitative studies. scent detection by animals, on the other hand, has been addressed in several d ...201623956311
the predictive value of gen-probe's amplified mycobacterium tuberculosis direct test compared with culturing in paraffin-embedded lymph node tissue exhibiting granulomatous inflammation and negative acid fast stain.the diagnosis of granulomatous inflammation with possible tuberculosis (tb) infection in histopathology is often difficult. there is a need for a rapid and reliable diagnostic test. thus, we evaluated the performance of the mycobacterium tuberculosis direct (mtd) test in specimens with granulomatous lymphadenitis and negative acid fast stains.201624602771
tuberculous pyomyositis: a re-emerging entity of many faces.tuberculosis (tb) has become a global concern due to its increasing incidence, particularly in immunocompromised patients, closely following the migratory patterns of populations. tb pyomyositis is a rare extrapulmonary manifestation of tb. its clinical presentation varies and requires a high degree of suspicion for early diagnosis. we present three patients diagnosed with tb pyomyositis: a 46-year-old man with dermatomyositis (dm) and hepatitis b who presented with fever, muscle weakness, and a ...201624609759
biosynthesis of mycobacterial lipids by polyketide synthases and beyond.over a decade ago, the analysis of the complete sequence of the genome of the human pathogen mycobacterium tuberculosis revealed an unexpectedly high number of open reading frames encoding proteins with homology to polyketide synthases (pkss). pkss form a large family of fascinating multifunctional enzymes best known for their involvement in the biosynthesis of hundreds of polyketide natural products with diverse biological activities. the surprising polyketide biosynthesis capacity of m. tuberc ...201624625105
evaluation of a modified direct agar proportion method for testing susceptibility of mycobacterium tuberculosis from mgit samples.the emergence of resistance to anti-tuberculosis (tb) drugs has become an obstacle to effective tb control. thus, there is an urgent need to identify patients and initiate adequate treatment for drug-resistant cases in a timely manner. the bactec mgit 960 system is well known for its rapid culturing time, and is in widespread use in taiwan. in this study, we evaluated the possibility of replacing the traditional indirect agar proportion method with a modified direct agar proportion method (mdapm ...201624662015
establishment of a new immunological method for direct detection of mycobacterium in solution.tuberculosis (tb) is a crucial health problem. prevention of the disease requires rapid diagnosis. rapid liquid culture systems, nucleic acid amplification tests, and high-performance liquid chromatography (hplc) are among the rapid tests used for detecting mycobacterium species. however, these tests are expensive and require extensive equipment and expertise, which is hardly affordable in resource-poor countries. although direct microscopy is performed routinely as an initial step for detection ...201624767420
contribution of increased isg15, isgylation and deregulated type i ifn signaling in usp18 mutant mice during the course of bacterial infections.host genetics has a key role in susceptibility to salmonella typhimurium infection. we previously used n-ethyl-n-nitrosourea (enu) mutagenesis to identify a loss-of-function mutation within the gene ubiquitin-specific peptidase 18 (usp18(ity9)), which confers increased susceptibility to salmonella typhimurium. usp18 functions to regulate type i interferon (ifn) signaling and as a protease to remove isg15 from substrate proteins. usp18(ity9) mice are susceptible to infection with salmonella typhi ...201624807690
[the role of imaging in thoracic tuberculosis].tuberculosis is an infectious disease mostly due to mycobacterium tuberculosis. it is frequent in developing countries and its incidence is rising in developed countries. lungs are the most involved organs of the chest but other structures can be affected. imaging is fundamental in the management of the disease. confirmation of diagnosis can be made only by bacteriologic and/or histologic exams. the first approach of diagnosis is based on clinical symptoms and chest x-ray signs. radiologic signs ...201624874403
development and characterization of spray-dried porous nanoaggregates for pulmonary delivery of anti-tubercular drugs.tuberculosis, mtb or tubercle bacillus (tb) is a lethal, infectious disease mainly caused by various strains of mycobacteria, usually mycobacterium tuberculosis. in this study, guar gum-based porous nanoaggregates were formulated by precipitation technique with two frontline antitubercular drugs, i.e. isoniazid and rifampicin. the formulations were optimized on the basis of various evaluation parameters such as morphology, density, entrapment efficiency and in vitro drug release. the optimized f ...201624870203
development of sandwich-form biosensor to detect mycobacterium tuberculosis complex in clinical sputum specimens.mycobacterium tuberculosis, the causing agent of tuberculosis, comes second only after hiv on the list of infectious agents slaughtering many worldwide. due to the limitations behind the conventional detection methods, it is therefore critical to develop new sensitive sensing systems capable of quick detection of the infectious agent. in the present study, the surface modified cadmium-telluride quantum dots and gold nanoparticles conjunct with two specific oligonucleotides against early secretor ...201625181404
additive effect of recombinant mycobacterium tuberculosis esat-6 protein and esat-6/cfp-10 fusion protein in adhesion of macrophages through fibronectin receptors.tuberculous granulomas are the sites of interaction between the t cells, macrophages, and extracellular matrix (ecm) to control the infection caused by mycobacterium tuberculosis (m. tuberculosis). a predominant role of rd-1-encoded secretory proteins, early secreted antigenic target-6 (esat-6), and culture filtrate protein-10 (cfp-10) in the formation of granulomas has recently been emphasized. however, the precise molecular events that induce the formation of these granulomatous structures are ...201625081983
a review of emerging trends in the treatment of tuberculosis.this review attempts to summarize the information available on emerging trends in the treatment of tuberculosis caused by the bacteria mycobacterium tuberculosis. nanostructured biomaterials, liposomes, microparticles and solid lipid nanoparticles have unique physicochemical properties such as particularly small and convenient size, sustained release, great surface area to mass ratio and high reactivity with structure. these properties can be useful in easing the administration of antimicrobial ...201625365354
[implementation of a telediagnostic system for tuberculosis and determination of multi-drug resistance based in the mods method in trujillo, peru].to implement a system for remote diagnosis of tuberculosis and multidrug resistance (mdr) using the microscopic-observation drug susceptibility assay (mods) method in the mycobacteria laboratory, trujillo center of excellence in tuberculosis (cenex-trujillo). the system included a variant of an algorithm for recognition of mycobacterium tuberculosis recently reported from digital images of mods cultures of sputum samples.201625418641
[impact of the migratory movements in the bacterial resistance to antibiotics].spain is among the main receptor countries for immigration; but there are few studies available which target antibiotic-resistance in immigrants. our objective was to review the current knowledge on the impact of antibiotic resistance in immigrants compared with the prevalence in the autochthonous population.201625418572
mucosal vaccination against tuberculosis using ag85a-loaded immunostimulating complexes.tuberculosis (tb) is one of the major devastating diseases in the world, mainly caused by mycobacterium tuberculosis. furthermore, multi-drug resistant tb and extremely drug resistant tb are becoming big problems globally. bacillus calmette-guerin (bcg) is the only available vaccine which provides protection against tb. the bcg vaccine is effective in children but not recommended in adults and elderly patients due to an associated low risk of infection with mycobacterium tuberculosis and variabl ...201625307269
comparison of cyp141 and is6110 for detection of mycobacterium tuberculosis from clinical specimens by pcr.tuberculosis is a major public health problem throughout the world. tb's worldwide patterns of prevalence coupled with the increase in incidence of hiv infection threaten the health and lives of humans worldwide. rapid detection of tb and the rapidly initiation of the administration of medication are important strategies for stopping the transmission of this disease transmission and its resistance to anti-tb drugs. molecular methods are advantageous relative to conventional techniques due to the ...201625304426
rapid screening of rpob and katg mutations in mycobacterium tuberculosis isolates by high-resolution melting curve analysis.early detection of multidrug-resistant tuberculosis (mdr-tb) is essential to prevent its transmission in the community and initiate effective anti-tb treatment regimen.201625297024
[immune reconstitution inflammatory syndrome related with infliximab interruption in patient with crohn's disease and active tuberculosis].tumor necrosis factor alpha inhibitors are associated with an increased risk of active tuberculosis. however, its interruption in this setting may trigger a paradoxical response to tuberculosis treatment, as an immune reconstitution inflammatory syndrome. we present the case of a 36-year-old patient, with crohn's disease, treated with infliximab for the last 8 years, who was admitted with miliary tuberculosis. a pan-susceptible mycobacterium tuberculosis strain was isolated. infliximab was inter ...201625298330
[characteristics of lung foci revealed by computed tomography in high-risk children and adolescents for tuberculosis].to give an x-ray pattern of single lung foci revealed by computed tomography (ct) in children and adolescents examined for tuberculosis.201625276882
microrna-124 inhibits the progression of adjuvant-induced arthritis in rats.micrornas (mirnas) are small endogenous, non-coding rnas that act as post-transcriptional regulators. we analysed the in vivo effect of mirna-124 (mir-124, the rat analogue of human mir-124a) on adjuvant-induced arthritis (aia) in rats.201625596157
head and neck tuberculosis: 6-year retrospective study.pulmonary involvement exists in 80% of cases of infection with mycobacterium tuberculosis; however, in up to 20% of cases there may be extra-pulmonary involvement. in the ent area, the most common site is cervical lymphadenitis, affecting approximately 95% of cases.201625630666
the effects of sp110's associated genes on fresh cavitary pulmonary tuberculosis in han chinese population.sp110 is a promising anti-mycobacterium tuberculosis (mtb) gene. to investigate the effects of sp110 and its associated genes, i.e., mybbp1a and rela, on pathological progression of mtb infection, an association study with 424 patients of fresh pulmonary tuberculosis (ptb) and 424 healthy controls was performed. moreover, classification and regression tree and multifactor dimensionality reduction were employed to explore the effects of gene-gene interactions on cavitary ptb. the results indicate ...201625612917
pharmacoinformatics analysis to identify inhibitors of mtb-asadh.aspartate-semialdehyde dehydrogenase (asadh; ec 1.2.1.11) is a key enzyme in the biosynthesis of essential amino acids in prokaryotes and fungi, inhibition of asadh leads to the development of novel antitubercular agents. in the present work, a combined structure and ligand-based pharmacophore modeling, molecular docking, and molecular dynamics (md) approaches were employed to identify potent inhibitors of mycobacterium tuberculosis (mtb)-asadh. the structure-based pharmacophore hypothesis consi ...201625565373
intracellular esat-6: a new biomarker for mycobacterium tuberculosis infection.early secreted antigenic target 6 (esat-6) is a virulent factor of mycobacterium tuberculosis (mtb). the identification of intracellular (i/c) esat-6 in host cells would be a direct marker of mtb infection. we developed a method to detect i/cesat-6 by flow cytometry. the aim of this study is to investigate the expression of i/cesat-6 in the host cells of individuals with mtb infection.201625545352
tuberculosis of the manubriosternal joint and concurrent asymptomatic active pulmonary tuberculosis in a patient presenting with a chest wall mass.a 62-year-old woman presented to our hospital with an anterior chest wall swelling. computed tomography (ct) and magnetic resonance imaging showed findings consistent with an infectious arthritis of the manubriosternal joint, and ct images also demonstrated multiple centrilobular nodules in both lungs, suggesting an infectious bronchiolitis. a ct-guided fine needle aspiration of a presternal mass yielded growth of mycobacterium tuberculosis. bronchoalveolar lavage confirmed an active pulmonary t ...201625457526
[analysis of genetic determinants of multidrug and extensively drug-resistant mycobacterium tuberculosis using oligonucleotide microchip].steadily growing resistance of the tuberculosis causative agent towards a broad spectrum of anti-tuberculosis drugs calls for rapid and reliable methods for identifying the genetic determinants responsible for this resistance. in this study, we present a biochip-based method for simultaneous identification of mutations within rpob gene associated with rifampin resistance, mutations in katg, inha, ahpc genes responsible for isoniazid resistance, mutations within the regions of gyra and gyrb genes ...201625850294
distinct strategies employed by dendritic cells and macrophages in restricting mycobacterium tuberculosis infection: different philosophies but same desire.dendritic cells (dcs) and macrophages (mϕs) are professional antigen-presenting cells (apcs) that can efficiently phagocytose mycobacterium tuberculosis (mtb), the etiological agent of tuberculosis (tb). it is quite interesting to mention here that dcs and mϕs use distinct strategies to combat and eliminate mtb. similarly, mtb employs different mechanisms to counteract the action of dcs and mϕs. mϕs are evolved with specialized, innate, defensive machinery to restrict growth of mtb at the initia ...201625793750
distribution and function of prophage phirv1 and phirv2 among mycobacterium tuberculosis complex.mycobacterium tuberculosis complex (mtbc) is notorious for causing diseases, such as tuberculosis. tuberculosis caused by m. tuberculosis remains a global public health concern. two prophages, phirv1 and phirv2, can be found among most mtbc genomes. however, no precise functions have been assigned for the two prophages. in this paper, to find out the function of these two prophages, the distribution and function of phirv1 and phirv2 in mtbc genomes were analyzed from multiple omics data. we foun ...201625855385
[role of laparoscopy in the diagnosis of peritoneal tuberculosis in endemic areas].the aim of our study is to demonstrate the difficulties of diagnosis of peritoneal tuberculosis in endemic areas and the value of laparoscopy for diagnostic confirmation. we report a retrospective study of 60 cases of peritoneal tuberculosis, collected from january 2004 to december 2009. the patients' median age was 41 years, and the sex ratio 0.4. the dominant reasons for consultation were pain and abdominal distension. abdominal ultrasound found ascites in all patients. computed tomography (ct ...201625787316
[computed tomography pattern of unchanged mediastinal lymph nodes in children with uninfected mycobacterium tuberculosis].to provide x-ray characteristics of mediastinal lymph nodes revealed by computed tomography (ct) in children and adolescents with uninfected mycobacterium tuberculosis.201625775884
targeting the cell wall of mycobacterium tuberculosis: a molecular modeling investigation of the interaction of imipenem and meropenem with l,d-transpeptidase 2.the single crystal x-ray structure of the extracellular portion of the l,d-transpeptidase (ex-ldtmt2 - residues 120-408) enzyme was recently reported. it was observed that imipenem and meropenem inhibit activity of this enzyme, responsible for generating l,d-transpeptide linkages in the peptidoglycan layer of mycobacterium tuberculosis. imipenem is more active and isothermal titration calorimetry experiments revealed that meropenem is subjected to an entropy penalty upon binding to the enzyme. h ...201625762064
the prospective evaluation of the tb strain typing service in england: a mixed methods study.in response to rising tb notification rates in england, universal strain typing was introduced in 2010. we evaluated the acceptability, effectiveness and cost-effectiveness of the tb strain typing service (tb-sts).201625882538
factors influencing delayed health care seeking among pulmonary tuberculosis suspects in rural communities in ntcheu district, malawi.delayed diagnosis and treatment of tuberculosis (tb) among individuals suspected of having tb may lead to continued transmission of mycobacterium tuberculosis in communities, higher mortality rates, and increase in government health expenditure because of prolonged illness due to late diagnosis and treatment initiation. the study explored factors leading to delayed health care seeking among individuals living in ntcheu district, malawi. two key informant interviews, 16 in-depth interviews, and t ...201626015428
synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives.a study concerning design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new fused derivatives with pyrrolo[2,1-c][4,7]phenanthroline skeleton is described. the strategy adopted for synthesis involves a [3 + 2] dipolar cycloaddition of several in situ generated 4,7-phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. stereo- and regiochemistry of cycloaddition reactions were discussed. the structure of the new compounds was proven unambiguou ...201625945747
genotypic characteristics of mycobacterium tuberculosis circulating in xinjiang, china.tuberculosis (tb), a chronic infectious disease caused by mycobacterium tuberculosis (mtb), poses a serious threat to human health. we investigated the genotypes of mtb in the high prevalence province xinjiang, china.201626414438
identifying areas and risk groups with localised mycobacterium tuberculosis transmission in northern england from 2010 to 2012: spatiotemporal analysis incorporating highly discriminatory genotyping data.information on geographical variation in localised transmission of tb can inform targeting of disease control activities. the aim of this study was to estimate the proportion of tb attributable to localised transmission for the period 2010-2012 in northern england and to identify case characteristics associated with spatiotemporal-genotypical clusters.201625920328
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