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stimulation through cd40 and tlr-4 is an effective host directed therapy against mycobacterium tuberculosis.tuberculosis (tb) is the leading cause of morbidity and mortality among all infectious diseases. failure of bacillus calmette guerin as a vaccine and serious side-effects and toxicity due to long-term tb drug regime are the major hurdles associated with tb control. the problem is further compounded by the emergence of drug-resistance strains of mycobacterium tuberculosis (mtb). consequently, it demands a serious attempt to explore safer and superior treatment approaches. recently, an improved un ...201627729911
risk factors for pulmonary cavitation in tuberculosis patients from china.pulmonary cavitation is one of the most frequently observed clinical characteristics in tuberculosis (tb). the objective of this study was to investigate the potential risk factors associated with cavitary tb in china. a total of 385 smear-positive patients were enrolled in the study, including 192 (49.9%) patients with cavitation as determined by radiographic findings. statistical analysis revealed that the distribution of patients with diabetes in the cavitary group was significantly higher th ...201627729644
new directions using reporter enzyme fluorescence (ref) as a tuberculosis diagnostic platform.although tuberculosis (tb) is one of the most common causes of morbidity and mortality in humans worldwide and diagnostic methods have been in place for more than 100 years, diagnosis remains a challenge. the main problems with diagnosis relate to the time needed to obtain a definitive result, difficulty in obtaining sputum, the primary clinical material used, and the ability of the causative agent, mycobacterium tuberculosis, to cause disease in nearly any tissue within the body. in order to de ...201627729258
sequencing-relative to hybridization-based transcriptomics approaches better define mycobacterium tuberculosis stress-response regulons.mycobacterium tuberculosis (mtb) infections cause tuberculosis (tb), an infectious disease which causes ∼1.5 million deaths annually. the ability of this pathogen to evade, escape and encounter immune surveillance is fueled by its adaptability. thus, mtb induces a transition in its transcriptome in response to environmental changes. global transcriptome profiling has been key to our understanding of how mtb responds to the different stress conditions it faces during its life cycle. while this wa ...201627729257
prevalence of mycobacterium tuberculosis among patients of hiv attending art centre. 201627728352
ecthyma gangrenosum-like lesions in a case of disseminated mycobacterium tuberculosis in a renal transplant recipient. 201627727755
epidemiology of mycobacterium tuberculosis infection in pavia province, lombardy, northern italy, 1998-2013.this study investigated the epidemiology of tuberculosis in the last 16 years in the province of pavia, lombardy, northern italy. the objective was to evaluate the clinical pattern of tuberculosis in immigrant groups compared with italians in an observational retrospective study conducted from 1998 to 2013. in all, 615 tuberculosis cases were admitted, 354 males (57.3%), median age 47-years, 425 (69.1%) italian-born patients, 190 (30.9%) immigrants. the ratio between the immigrant group and the ...201627727403
non-human primate models of tuberculosis.among the animal models of tuberculosis (tb), the non-human primates, particularly rhesus macaques (macaca fascicularis) and cynomolgus macaques (macaca mulatta), share the greatest anatomical and physiological similarities with humans. macaques are highly susceptible to mycobacterium tuberculosis infection and manifest the complete spectrum of clinical and pathological manifestations of tb as seen in humans. therefore, the macaque models have been used extensively for investigating the pathogen ...201627726820
mycobacteria.the immunocompromised host is at increased risk of mycobacterium tuberculosis complex and nontuberculous mycobacteria infection. although mycobacterium tuberculosis complex is a significant mycobacterial pathogen, nontuberculous mycobacteria causes substantial disease in those with suppressed immune responses. mycobacterial infections can cause significant morbidity and mortality in this patient population, and rapid identification and susceptibility testing of the mycobacterial species is param ...201627726808
the evolutionary history, demography, and spread of the mycobacterium tuberculosis complex.with the advent of next-generation sequencing technology, the genotyping of clinical mycobacterium tuberculosis strains went through a major breakup that dramatically improved the field of molecular epidemiology but also revolutionized our deep understanding of the m. tuberculosis complex evolutionary history. the intricate paths of the pathogen and its human host are reflected by a common geographical origin in africa and strong biogeographical associations that largely reflect the past migrati ...201627726798
mouse and guinea pig models of tuberculosis.this article describes the nature of the host response to mycobacterium tuberculosis in the mouse and guinea pig models of infection. it describes the great wealth of information obtained from the mouse model, reflecting the general availability of immunological reagents, as well as genetic manipulations of the mouse strains themselves. this has led to a good understanding of the nature of the t-cell response to the infection, as well as an appreciation of the complexity of the response involvin ...201627726797
human immunology of tuberculosis.immunology is a central theme when it comes to tuberculosis (tb). the outcome of human infection with mycobacterium tuberculosis is dependent on the ability of the immune response to clear or contain the infection.in cases where this fails, the bacterium replicates, disseminates within the host, and elicits a pathologic inflammatory response, and disease ensues. clinical presentation of tb disease is remarkably heterogenous, and the disease phenotype is largely dependent on host immune status. o ...201627726784
oxidative unfolding of the rubredoxin domain and the natively disordered n-terminal region regulate the catalytic activity of mycobacterium tuberculosis protein kinase g.mycobacterium tuberculosis escapes killing in human macrophages by secreting protein kinase g (pkng). pkng intercepts host signaling to prevent fusion of the phagosome engulfing the mycobacteria with the lysosome and, thus, their degradation. the n-terminal nors (no regulatory secondary structure) region of pkng (approximately residues 1-75) has been shown to play a role in pkng regulation by (auto)phosphorylation, whereas the following rubredoxin-like metal-binding motif (rd, residues ∼74-147) ...201627810897
dna antenna tile-associated deoxyribozyme sensor with improved sensitivity.some natural enzymes increase the rate of diffusion-limited reactions by facilitating substrate flow to their active sites. inspired by this natural phenomenon, we developed a strategy for efficient substrate delivery to a deoxyribozyme (dz) catalytic sensor. this resulted in a three- to fourfold increase in sensitivity and up to a ninefold improvement in the detection limit. the reported strategy can be used to enhance catalytic efficiency of diffusion-limited enzymes and to improve sensitivity ...201627620365
first evaluation of quantiferon-tb gold plus performance in contact screening.identifying latently infected individuals is crucial for the elimination of tuberculosis (tb). we evaluated for the first time the performance of a new type of interferon-γ release assay, quantiferon-tb plus (qft-plus), which includes an additional antigen tube (tb2), stimulating both cd4(+) and cd8(+) t-cells in contacts of tb patients.contacts were screened for latent tb infection by tuberculin skin test, qft-plus and quantiferon-tb gold in tube (qft-git).in 119 tb contacts, the overall agreem ...201627390280
detection of transrenal dna for the diagnosis of pulmonary tuberculosis and treatment monitoring.molecular diagnostics of patients with mtb tuberculosis from urine samples.201627798774
mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages.generalist and specialist species differ in the breadth of their ecological niches. little is known about the niche width of obligate human pathogens. here we analyzed a global collection of mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. we show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. population genomic analyses sh ...201627798628
genomic diversity in autopsy samples reveals within-host dissemination of hiv-associated mycobacterium tuberculosis.mycobacterium tuberculosis remains a leading cause of death worldwide, especially among individuals infected with hiv. whereas phylogenetic analysis has revealed m. tuberculosis spread throughout history and in local outbreaks, much less is understood about its dissemination within the body. here we report genomic analysis of 2,693 samples collected post mortem from lung and extrapulmonary biopsies of 44 subjects in kwazulu-natal, south africa, who received minimal antitubercular treatment and m ...201627798613
molecular diversity of mycobacterium tuberculosis strains in northwestern iran.years after the development of antituberculosis (tb) drugs, many people continue to suffer from this disease. to control the spread of tb, strains of the mycobacterium tuberculosis complex need to be determined, and sources of infection must be identified. such steps should help to prevent transmission of the infection.201627800145
[the system of matrix metalloproteinases and their role in patients with pulmonary tuberculosis].the aim of this study was to examine the relationship between serum levels of parameters of the system metalloproteinase (mmp)/inhibitors with severity of infiltrative pulmonary tuberculosis (itl), changes in examined parameters during the intensive phase treatment (ipt), as well as possibility of their use for prediction of ipt effectiveness, along with acute-phase proteins (afp). the study included itl patients which were subdivided into two groups (i and ii) with different rates of reparative ...201627797337
animal-adapted members of the <i>mycobacterium tuberculosis</i> complex endemic to the southern african subregion.members of the mycobacterium tuberculosis complex (mtc) cause tuberculosis (tb) in both animals and humans. in this article, three animal-adapted mtc strains that are endemic to the southern african subregion - that is, mycobacterium suricattae, mycobacterium mungi, and the dassie bacillus - are reviewed with a focus on clinical and pathological presentations, geographic distribution, genotyping methods, diagnostic tools and evolution. moreover, factors influencing the transmission and establish ...201627796109
pharmacological inhibition of host heme oxygenase-1 suppresses mycobacterium tuberculosis infection in vivo by a mechanism dependent on t lymphocytes.heme oxygenase-1 (ho-1) is a stress response antioxidant enzyme which catalyzes the degradation of heme released during inflammation. ho-1 expression is upregulated in both experimental and human mycobacterium tuberculosis infection, and in patients it is a biomarker of active disease. whether the enzyme plays a protective versus pathogenic role in tuberculosis has been the subject of debate. to address this controversy, we administered tin protoporphyrin ix (snppix), a well-characterized ho-1 e ...201627795400
mycosins are required for the stabilization of the esx-1 and esx-5 type vii secretion membrane complexes.pathogenic mycobacteria contain up to five type vii secretion (t7s) systems, esx-1 to esx-5. one of the conserved t7s components is the serine protease mycosin (mycp). strikingly, whereas mycp is essential for secretion, the protease activity of mycp1 in mycobacterium tuberculosis has been shown to be dispensable for secretion. the essential role of mycp therefore remains unclear. here we show that mycp1 and mycp5 of m. marinum have similar phenotypes, confirming that mycp has a second unknown f ...201627795391
eis promoter c14g and c15g mutations do not confer kanamycin resistance in mycobacterium tuberculosis.we studied the significance of particular eis mutations on mycobacterium tuberculosis drug resistance using a specialized transduction strategy. recombinant strains harboring eis promoter mutations c14t, c12t, and g10a exhibited kanamycin resistance with mics of 40, 10, and 20 μg/ml, respectively, while recombinant strains harboring c14g and c15g mutations were kanamycin susceptible (mic, 2.5 to 5 μg/ml). each of the eis mutants tested remained amikacin susceptible (mic, 0.5 to 4 μg/ml). the ide ...201627736762
xpert mtb/rif assay shows faster clearance of mycobacterium tuberculosis dna with higher levels of rifapentine exposure.the xpert mtb/rif assay is both sensitive and specific as a diagnostic test. xpert also reports quantitative output in cycle threshold (ct) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. we evaluated the relationship between xpert ct trajectory and drug exposure during tuberculosis (tb) treatment to assess the potential utility of xpert ct for treatment monitoring. we obtained serial sputum samples from patients with smear-positive pulmonary tb w ...201627733634
evaluation of the abbott realtime mtb and realtime mtb inh/rif assays for direct detection of mycobacterium tuberculosis complex and resistance markers in respiratory and extrapulmonary specimens.the abbott realtime mtb (rt mtb) assay is a new automated nucleic acid amplification test for the detection of mycobacterium tuberculosis complex (mtbc) in clinical specimens. in combination with the realtime mtb inh/rif (rt mtb inh/rif) resistance assay, which can be applied to rt mtb-positive specimens as an add-on assay, the tests also indicate the genetic markers of resistance to isoniazid (inh) and rifampin (rif). we aimed to evaluate the diagnostic sensitivity and specificity of rt mtb usi ...201627733630
polymorphisms in the prostaglandin receptor ep2 gene confers susceptibility to tuberculosis.prostaglandin e2 (pge2) is an important lipid mediator of the inflammatory immune response during acute and chronic infections. pge2 modulates a variety of immune functions via four receptors (ep1-ep4), which mediate distinct pge2 effects. mice lacking ep2 are more susceptible to infection by mycobacterium tuberculosis (m.tb), have a higher bacterial load, and increase size and number of granulomatous lesions. our aim was to assess whether single nucleotide polymorphisms (snps) in ep2 increase t ...201627780787
"genetic regulation of mycobacterium tuberculosis in a lipid-rich environment".tuberculosis (tb) remains as one of the leading causes of morbidity and mortality among infectious diseases worldwide. although lipids (mainly fatty acids and cholesterol) have been reported to play an important role during active and latent infection of m. tuberculosis, there are other molecular aspects of bacterial response to those substrates that are not fully understood, involving gene regulation background. this review highlights recent insights on pathogen gene expression: regulation duri ...201627771519
association of mycobacterium infections in patients with mendelian susceptibility to mycobacterial disease with venous thromboembolism.an association between a hypercoagulable state and mendelian susceptibility to mycobacterial disease (msmd) has been established in a few studies; resultant thrombosis is considered rare. in a case-control study, the prevalence of factor v leiden, prothrombin g20210a and methylenetetrahydrofolate reductase (mthfr) c677t, a1298c mutations were investigated in mycobacterium-infected patients. the study comprised 30 patients with mycobacterial infections (invasive, disseminated and/or recurrent inf ...201627686649
natural compounds for overcoming multidrug resistance in mycobacteria.tuberculosis caused by mycobacterium tuberculosis (mtb) is currently a major health concern due to its growing mortality rates around the world. the known anti-tb drugs although are available for the treatment but it produces adverse side effects on the human health and are also not very cost effective. moreover, emergence of multidrug resistance (mdr) phenomenon has also compromised their activities.201627652611
structural and genetic analyses of the mycobacterium tuberculosis protein kinase b sensor domain identify a potential ligand-binding site.monitoring the environment with serine/threonine protein kinases is critical for growth and survival of mycobacterium tuberculosis, a devastating human pathogen. protein kinase b (pknb) is a transmembrane serine/threonine protein kinase that acts as an essential regulator of mycobacterial growth and division. the pknb extracellular domain (ecd) consists of four repeats homologous to penicillin-binding protein and serine/threonine kinase associated (pasta) domains, and binds fragments of peptidog ...201627601474
monocyte-derived dendritic cells early exposed to mycobacterium tuberculosis induce an enhanced t helper 17 response and transfer mycobacterial antigens.tuberculosis (tb) is a complex disease, and the success of the bacterium depends on its ability to evade the immune response. previously, we determined that mycobacterium tuberculosis (mtb) impairs the function of dendritic cells (dc), promoting the generation of cells that are poor stimulators of mycobacterial antigen-specific cd4t cells, which are required to control this persistent infection. in this study, we aimed to determine the mechanisms by which monocyte-derived dcs differentiated in t ...201627394957
toll-like receptor 2 in host defense against mycobacterium tuberculosis: to be or not to be-that is the question.toll-like receptor (tlr) 2 is expressed on immune cells and respiratory epithelial cells lining the lung. tlr2 is not critical for protection during acute mycobacterium tuberculosis (mtb) infection but it has a significant multi-faceted role in containing chronic infection. this review highlights the contribution of tlr2 to host protection, immune evasion by mtb and immune regulation during chronic mtb infection. the tlr2-triggered pro-inflammatory cytokines initiate protective mechanisms and li ...201627326654
substantial molecular evolution and mutation rates in prolonged latent mycobacterium tuberculosis infection in humans.the genome of mycobacterium tuberculosis (mtb) of latently infected individuals may hold the key to understanding the processes that lead to reactivation and progression to clinical disease. we report here analysis of pairs of mtb isolates from putative prolonged latent tb cases. we identified two confirmed cases, and used whole genome sequencing to investigate the mutational processes that occur over decades in latent mtb. we found an estimated mutation rate between 0.2 and 0.3 over 33 years, s ...201627296510
clinical and laboratory differences between lymphocyte- and neutrophil-predominant pleural tuberculosis.pleural tuberculosis (tb), a form of extrapulmonary tb, can be difficult to diagnose. high numbers of lymphocytes in pleural fluid have been considered part of the diagnostic criteria for pleural tb; however, in many cases, neutrophils rather than lymphocytes are the predominant cell type in pleural effusions, making diagnosis more complicated. additionally, there is limited information on the clinical and laboratory characteristics of neutrophil-predominant pleural effusions caused by mycobacte ...201627788218
cytokine neutralization at specific cellular source : a new therapeutic paradigm?currently, treatment of autoimmune diseases is based on manipulation of general control mechanisms, including those mediated by immunoregulatory cytokines. this approach is non-curative and may cause unwanted side effects due to numerous beneficial and non-redundant functions of a particular cytokine.201627787607
evolution of mycobacterium tuberculosis: new insights into pathogenicity and drug resistance.the tuberculosis agent mycobacterium tuberculosis has undergone a long and selective evolution toward human infection and represents one of the most widely spread pathogens due to its efficient aerosol-mediated human-to-human transmission. with the availability of more and more genome sequences, the evolutionary trajectory of this obligate pathogen becomes visible, which provides us with new insights into the molecular events governing evolution of the bacterium and its ability to accumulate dru ...201627787194
the role of host genetics (and genomics) in tuberculosis.familial risk of tuberculosis (tb) has been recognized for centuries. largely through studies of mono- and dizygotic twin concordance rates, studies of families with mendelian susceptibility to mycobacterial disease, and candidate gene studies performed in the 20th century, it was recognized that susceptibility to tb disease has a substantial host genetic component. limitations in candidate gene studies and early linkage studies made the robust identification of specific loci associated with dis ...201627787193
the frequency distribution of vitamin d receptor fok i gene polymorphism among ugandan pulmonary tb patients.background:mycobacterium tuberculosis (tb) is still a major problem globally and especially in africa. vitamin d deficiency has been linked to tb in the past and studies have found vitamin d deficiency to be common among ugandan tb patients. the functional activity of vitamin d is dependent on the genotype of the vitamin d receptor (vdr) polymorphic genes. recent findings have indicated that vdr polymorphisms may cause increased resistance or susceptibility to tb. the vitamin d ligand and its re ...201627785354
tuberculosis.tuberculosis (tb) is an airborne infectious disease caused by organisms of the mycobacterium tuberculosis complex. although primarily a pulmonary pathogen, m. tuberculosis can cause disease in almost any part of the body. infection with m. tuberculosis can evolve from containment in the host, in which the bacteria are isolated within granulomas (latent tb infection), to a contagious state, in which the patient will show symptoms that can include cough, fever, night sweats and weight loss. only a ...201627784885
erythema nodosum and the risk of tuberculosis in a high incidence setting.this study estimates the erythema nodosum (en) incidence in a tuberculosis (tb) endemic setting and evaluates the likelihood of a subsequent tb diagnosis among individuals with mycobacterium tuberculosis infection (mti) with or without en.201627784508
[research of pyrazinamide resistance of mycobacterium tuberculosis]. 201627784505
mechanisms of first-line antimicrobial resistance in multi-drug and extensively drug resistant strains of mycobacterium tuberculosis in kwazulu-natal, south africa.in south africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal hiv pandemic.201627784282
the assessment of host and bacterial proteins in sputum from active pulmonary tuberculosis.pulmonary tuberculosis (tb) is caused by mycobacterium tuberculosis. the protein composition of sputum may reflect the immune status of the lung. this study aimed to evaluate the protein profiles in spontaneous sputum samples from patients with active pulmonary tb. sputum samples were collected from patients with pulmonary tb and healthy controls. western blotting was used to analyze the amount of interleukin 10 (il-10), interferon-gamma (ifn-γ), il-25, il-17, perforin-1, urease, albumin, transf ...201627796930
infectiousness of hiv-seropositive patients with tuberculosis in a high-burden african setting.policy recommendations on contact investigation of hiv-seropositive patients with tuberculosis have changed several times. current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of hiv-seropositive and -seronegative index cases have been performed in sub-saharan africa.201627181053
magnetic resonance imaging and genexpert: a rapid and accurate diagnostic tool for the management of tuberculosis of the spine.retrospective study.201627790312
performance of the bact alert 3d system versus solid media for recovery and drug susceptibility testing of mycobacterium tuberculosis in a tertiary hospital in korea.tuberculosis (tb) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (mdr) and extended drug-resistant (xdr) tb is important for appropriate treatment. in this study, performances of solid and liquid culture methods were compared with respect to mdr- and xdr-tb isolate recovery and drug susceptibility testing.201627790280
tuberculosis infection and latent tuberculosis.active tuberculosis (tb) has a greater burden of tb bacilli than latent tb and acts as an infection source for contacts. latent tuberculosis infection (ltbi) is the state in which humans are infected with mycobacterium tuberculosis without any clinical symptoms, radiological abnormality, or microbiological evidence. tb is transmissible by respiratory droplet nucleus of 1-5 µm in diameter, containing 1-10 tb bacilli. tb transmission is affected by the strength of the infectious source, infectious ...201627790271
draft genome sequences of two drug-resistant mycobacterium tuberculosis isolates from myanmar.multidrug-resistant tuberculosis (mdr-tb) and lately, extensively drug-resistant tb (xdr-tb) are increasing global health concerns. here, we present the genome sequences of two mdr-tb isolates from myanmar, one of 27 countries with a high mdr-tb burden, and describe a number of mutations consistent with these being xdr-tb isolates.201627789629
a metabolomics investigation of the function of the esx-1 gene cluster in mycobacteria.the esx-1 gene cluster, encoding the type-vii secretion (t7s) system and its virulence associated proteins, esat-6 and cfp-10, is thought to be responsible for the transport of extracellular proteins across the hydrophobic and highly impermeable, cell envelope of mycobacterium, and is involved in virulence in mycobacterium tuberculosis, the causative agent of tuberculosis. using a gcxgc-tofms metabolomics approach, a m. smegmatis esx-1 knock-out strain (δesx-1ms) was compared to that of the m. s ...201627744102
a novel missense mutation in the nadph binding domain of cybb abolishes the nadph oxidase activity in a male patient with increased susceptibility to infections.chronic granulomatous disease (cgd) is a primary immunodeficiency caused by mutations in the five structural genes (cybb, cyba, ncf1, ncf2, and ncf4) that typically results in a decrease in function or inability to generate a respiratory burst, leading to defective killing of pathogens, including fungi and intracellular bacteria. mutations in cybb, encoding the gp91phox (also known as nox2) result in x-linked cgd account for approximately 65% of cgd cases. here, we aimed the characterization of ...201627666509
mirna-155 and mirna-132 as potential diagnostic biomarkers for pulmonary tuberculosis: a preliminary study.in our study, we aimed to profile a panel micrornas (mirnas) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (ptb) and to illuminate the molecular mechanisms in the development of ptb. firstly, gene expression profile of e-geod-49951 was downloaded from arrayexpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between mirnas of mycobacterium tuberculosis (mtb)-infected individuals and healthy subje ...201627616444
the essential mycobacterial amidotransferase gatcab is a modulator of specific translational fidelity.although regulation of translation fidelity is an essential process(1-7), diverse organisms and organelles have differing requirements of translational accuracy(8-15), and errors in gene translation serve an adaptive function under certain conditions(16-20). therefore, optimal levels of fidelity may vary according to context. most bacteria utilize a two-step pathway for the specific synthesis of aminoacylated glutamine and/or asparagine trnas, involving the glutamine amidotransferase gatcab(21-2 ...201627564922
nk-cd11c+ cell crosstalk in diabetes enhances il-6-mediated inflammation during mycobacterium tuberculosis infection.in this study, we developed a mouse model of type 2 diabetes mellitus (t2dm) using streptozotocin and nicotinamide and identified factors that increase susceptibility of t2dm mice to infection by mycobacterium tuberculosis (mtb). all mtb-infected t2dm mice and 40% of uninfected t2dm mice died within 10 months, whereas all control mice survived. in mtb-infected mice, t2dm increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those ...201627783671
real time pcr for the rapid identification and drug susceptibility of mycobacteria present in bronchial washings.mycobacteria have a spectrum of virulence and different susceptibilities to antibiotics. distinguishing mycobacterial species is vital as patients with non-tuberculous mycobacterial (ntm) infections present clinical features that are similar to those of patients with tuberculosis. thus, rapid differentiation of mycobacterium tuberculosis complex from ntm is critical to administer appropriate treatment. hence the aim of the study was to rapid identification of mycobacterial species present in bro ...201627782812
metabolic reprogramming & inflammation: fuelling the host response to pathogens.successful immune responses to pathogens rely on efficient host innate processes to contain and limit bacterial growth, induce inflammatory response and promote antigen presentation for the development of adaptive immunity. this energy intensive process is regulated through multiple mechanisms including receptor-mediated signaling, control of phago-lysomal fusion events and promotion of bactericidal activities. inherent macrophage activities therefore are dynamic and are modulated by signals and ...201627780657
the global burden of latent tuberculosis infection: a re-estimation using mathematical modelling.the existing estimate of the global burden of latent tb infection (ltbi) as "one-third" of the world population is nearly 20 y old. given the importance of controlling ltbi as part of the end tb strategy for eliminating tb by 2050, changes in demography and scientific understanding, and progress in tb control, it is important to re-assess the global burden of ltbi.201627780211
very low doses of mycobacterium tuberculosis yield diverse host outcomes in common marmosets (callithrix jacchus).identifying and refining small-animal models of tuberculosis that recapitulate aspects of human mycobacterium tuberculosis infection can contribute to advancing our understanding of critical facets of the disease. to study the effects of very low-dose infections with 2 strains of m. tuberculosis on disease progression and survival in common marmosets, animals were challenged with strains erdman and cdc1551 at doses ranging from 1 to 12 cfu. these data revealed that the susceptibility of marmoset ...201627780009
pyrazinamide susceptibility testing in mycobacterium tuberculosis using the fast resazurin microtiter assay plate.department of clinical analysis and biomedicine, state university of maringa, maringa, pr, brazil.201627776597
molecular typing of mycobacteria isolated from tuberculous lymphadenitis cases in addis ababa, ethiopia.in ethiopia, one of the world's 22 high tuberculosis (tb) burden countries, one third of the tuberculosis (tb) cases are attributed to tuberculosis lymphadenitis (tbln). however, information on the molecular type of the mycobacterial species and strains that cause tbln in the country is scarce.201627776596
carbapenems against mycobacterium tuberculosis: a review of the evidence.carbapenems, a more recent β-lactam class, represent a unique anti-tuberculosis option, as emerging evidence demonstrates that they target the mycobacterium tuberculosis cell wall and β-lactamase. this provides a potentially new agent against m. tuberculosis, in particular for multidrug-resistant (mdr) and extensively drug-resistant (xdr) tuberculosis (tb), where options are limited. in this review, we examine the current evidence on the activity of carbapenems against m. tuberculosis. the predo ...201627776583
the cox- inhibitor indomethacin reduces th1 effector and t regulatory cells in vitro in mycobacterium tuberculosis infection.tuberculosis (tb) causes a major burden on global health with long and cumbersome tb treatment regimens. host-directed immune modulating therapies have been suggested as adjunctive treatment to tb antibiotics. upregulated cyclooxygenase-2 (cox-2)-prostaglandin e2 (pge2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of mycobacterium tuberculosis (mtb).201627776487
a simplified mycobacterial growth inhibition assay (mgia) using direct infection of mouse splenocytes and the mgit system.we describe a simplified mycobacterial growth inhibition assay (mgia) for pre-clinical assessment of vaccine-mediated protection in mice. the assay is accomplished by directly infecting splenocytes from vaccinated mice with mycobacterium tuberculosis and quantifying mycobacteria using mycobacterial growth indicator tubes (mgit). vaccine-mediated immunogenicity detected by this assay correlated with protection.201627650198
human tuberculosis i. epidemiology, diagnosis and pathogenetic mechanisms.mycobacterium tuberculosis (m. tuberculosis), an almost genetically monomorphic pathogen is a human parasite, transmitted mostly by humans and causes tuberculosis (tb). tb is firmly associated to poverty, although lack of proper nutrition and lowered immune status are contributing factors for disease development. tb remains second only to hiv/aids as the leading cause of mortality worldwide due to a single infectious agent and is responsible for nearly 1.5 million deaths annually. some steps of ...201627281297
tuberculous arthritis of the hip with staphylococcus aureus superinfection.skeletal tuberculosis (tb) accounts for a small percentage of all cases of tb. it is often difficult to diagnose, especially in the hip joint. tb arthritis can be masked by superinfection with other pathogens, leading to a delay in diagnosis and treatment. trauma or surgery is a reported risk factor of tb arthritis. in contrast, descriptions of tb arthritis after a closed bone fracture are rare. we herein report a case involving an 81-year-old woman with septic arthritis superinfected with methi ...201627221797
a diagnosis of disseminated tuberculosis based on knee arthroscopic guided synovial biopsy in the context of monoarthritis.accounting for 2.2-4.7% of all tuberculosis cases in europe and usa and around 10-15% of extra-pulmonary tuberculosis cases, osteoarticular tuberculosis tends to be chronic, slowly progressive and destructive. we report the case of an 81-year-old male with 3 weeks of progressively worsening pain, swelling and limited range of motion of the left knee. a knee arthroscopy was performed for synovial biopsy at our department revealing diffuse synovitis with scarce villi formation. the positive polyme ...201627155318
[analysis of the numbers and subsets of mtb-hag specific tnf-α(+) γδ t cells in peripheral blood of patients with active pulmonary tuberculosis].objective to investigate the differences of proportions of tumor necrosis factor α (tnf-α)-producing cells in peripheral blood γδ t cells stimulated with mycobacterium tuberculosis heat resistant antigen (mtb-hag) among patients with pulmonary tuberculosis (ptb), latent tuberculosis infection (ltbi) and healthy subjects (hc). methods the peripheral blood specimens were collected from 15 normal adults, which were divided into hc group (n=9) and ltbi group (n=6), by enzyme-linked immunospot (elisp ...201627774949
experimental models of foamy macrophages and approaches for dissecting the mechanisms of lipid accumulation and consumption during dormancy and reactivation of tuberculosis.despite a slight decline since 2014, tuberculosis (tb) remains the major deadly infectious disease worldwide with about 1.5 million deaths each year and with about one-third of the population being latently infected with mycobacterium tuberculosis, the etiologic agent of tb. during primo-infection, the recruitment of immune cells leads to the formation of highly organized granulomas. among the different cells, one outstanding subpopulation is the foamy macrophage (fm), characterized by the abund ...201627774438
in vitro and in vivo antimycobacterial, hepatoprotective and immunomodulatory activity of euclea natalensis and its mode of action.the natal gwarri or natal ebony (euclea natalensis a.dc.) is a deciduous tree found widespread throughout southern africa, especially in kwazulu-natal and the southern cost. it has been widely used by indigenous communities such as the zulus, tsongas and vendas for symptoms related to tuberculosis (tb). the decoctions made from the plant parts are administered for chest diseases to treat complications such as chest pains, bronchitis, pleurisy and asthma. tb is prevalent in immune-compromised pat ...201627773800
tuberculosis: an infection-initiated autoimmune disease?tuberculosis (tb) is caused by mycobacterium tuberculosis (mtb) and provided original proof that an infectious agent can cause human disease. however, key steps in tb pathogenesis remain poorly understood. we propose that autoimmunity is a critical and overlooked process driving pathology in tb, and present clinical and experimental observations supporting this hypothesis.201627773684
novel lipopeptides of esat-6 induce strong protective immunity against mycobacterium tuberculosis: routes of immunization and tlr agonists critically impact vaccine's efficacy.mycobacterium tuberculosis (mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. the development of a new vaccine against mtb is essential to control global spread of tuberculosis, since the current vaccine bcg is not very effective and antibiotic resistance is a serious, burgeoning problem. esat-6 is a secreted protein of mtb, which is absent in bcg but has been implicated in inducing protective immunity against mtb. peptide based subunit vaccines are attractive d ...201627693020
granulomas and inflammation: host-directed therapies for tuberculosis.tuberculosis (tb) remains a leading global health problem that is aggravated by emergence of drug-resistant strains, which account for increasing number of treatment-refractory cases. thus, eradication of this disease will strongly require better therapeutic strategies. identification of host factors promoting disease progression may accelerate discovery of adjunct host-directed therapies (hdts) that will boost current treatment protocols. hdts focus on potentiating key components of host anti-m ...201627822210
transcriptomic biomarkers for tuberculosis: evaluation of dock9. epha4, and npc2 mrna expression in peripheral blood.lately, much effort has been made to find mrna biomarkers for tuberculosis (tb) disease/infection with microarray-based approaches. in a pilot investigation, through rna sequencing technology, we observed a prominent modulation of dock9, epha4, and npc2 mrna abundance in the blood of tb patients. to corroborate these findings, independent validations were performed in cohorts from different areas. gene expression levels in blood were evaluated by quantitative real-time pcr (brazil, n = 129) or r ...201627826286
gene-based neonatal immune priming potentiates a mucosal adenoviral vaccine encoding mycobacterial ag85b.tuberculosis remains a major public health hazard worldwide, with neonates and young infants potentially more susceptible to infection than adults. bcg, the only vaccine currently available, provides some protection against tuberculous meningitis in children but variable efficacy in adults, and is not safe to use in immune compromised individuals. a safe and effective vaccine that could be given early in life, and that could also potentiate subsequent booster immunization, would represent a sign ...201627823900
a high fundamental frequency (hff)-based qcm immunosensor for tuberculosis detection.tuberculosis, one of the oldest diseases affecting human beings, is still considered as a world public health problem by the world health organization. therefore, there is a need for new and more powerful analytical methods for early illness diagnosis. with this idea in mind, the development of a high fundamental frequency (hff) piezoelectric immunosensor for the sensitive detection of tuberculosis was undertaken. a 38 kda protein secreted by mycobacterium tuberculosis was first selected as the ...201627823567
synthesis, antitubercular and anticancer activities of p-nitrophenylethylenediamine-derived schiff bases.schiff bases have been greatly studied in biological field due to their wide range of pharmacological activities, such as antitubercular and antitumour. in the search of novel antitubercular agents, several compounds containing pharmacophoric group of ethambutol have been synthesized and evaluated against mycobacteria species causing tuberculosis. in this work, we investigate whether ethylenediamine, schiff base as well as nitro group together could contribute to the formation of novel molecules ...201627823561
impact of genetic diversity on the biology of mycobacterium tuberculosis complex strains.tuberculosis (tb) remains the most deadly bacterial infectious disease worldwide. its treatment and control are threatened by increasing numbers of multidrug-resistant (mdr) or nearly untreatable extensively drug-resistant (xdr) strains. new concepts are therefore urgently needed to understand the factors driving the tb epidemics and the spread of different strain populations, especially in association with drug resistance. classical genotyping and, more recently, whole-genome sequencing (wgs) r ...201627837742
phenotypic heterogeneity in mycobacterium tuberculosis.the interaction between the host and the pathogen is extremely complex and is affected by anatomical, physiological, and immunological diversity in the microenvironments, leading to phenotypic diversity of the pathogen. phenotypic heterogeneity, defined as nongenetic variation observed in individual members of a clonal population, can have beneficial consequences especially in fluctuating stressful environmental conditions. this is all the more relevant in infections caused by mycobacterium tube ...201627837741
microwave-assisted zrsio2 catalysed synthesis, characterization and computational study of novel spiro[indole-thiazolidines] derivatives as anti-tubercular agents.in the current investigation, we prepared a series of novel spiro[indole-thiazolidines] derivatives (5a-5h) from 5-substituted isatin derivatives and thioglycolic acid (tga) with zrsio2 as an efficient catalyst under microwave irradiation. the significant merits of this protocol have some significant merits such as simplicity in operation, simple, efficient workup, good practical yields of product and the employment of recyclable catalyst. all the new synthesized scaffold has been well character ...201627837427
early whole blood transcriptional signatures are associated with severity of lung inflammation in cynomolgus macaques with mycobacterium tuberculosis infection.whole blood transcriptional profiling offers great diagnostic and prognostic potential. although studies identified signatures for pulmonary tuberculosis (tb) and transcripts that predict the risk for developing active tb in humans, the early transcriptional changes immediately following mycobacterium tuberculosis infection have not been evaluated. we evaluated the gene expression changes in the cynomolgus macaque model of tb, which recapitulates all clinical aspects of human m. tuberculosis inf ...201627837110
impact of hypoxia on drug resistance and growth characteristics of mycobacterium tuberculosis clinical isolates.mycobacterium tuberculosis (mtb) is a specific aerobic bacterium, but can survive under hypoxic conditions, such as those in lung cheese necrosis, granulomas, or macrophages. it is not clear whether the drug sensitivity and growth characteristics of mtb under hypoxic conditions are different from those under aerobic conditions. in this study, we examined the drug resistance and growth characteristics of mtb clinical isolates by a large sample of in vitro drug susceptibility tests, using an autom ...201627835653
mechanisms of mycobacterial transmission: how does mycobacterium tuberculosis enter and escape from the human host. 201627831741
the development of small-molecule modulators for clpp protease activity.the global spread of antibiotic resistance among important human pathogens emphasizes the need to find new antibacterial drugs with a novel mode of action. the clpp protease has been shown to demonstrate its pivotal importance to both the survival and the virulence of pathogenic bacteria during host infection. deregulating clpp activity either through overactivation or inhibition could lead to antibacterial activity, declaiming the dual molecular mechanism for small-molecule modulation. recently ...201627831584
qsar studies, synthesis and antibacterial assessment of new inhibitors against multidrug-resistant mycobacterium tuberculosis.this paper describes quantitative structure-activity relationships (qsar) studies using artificial neural networks (ann), synthesis and in vitro antitubercular activity of several potent compounds against h37rv and resistant mycobacterium tuberculosis (mtb) strains. eight qsar models were built using various types of descriptors with four publicly available structurally diverse datasets, including recent data from pubchem and chembl. the predictive power of the obtained qsar models was evaluated ...201627829331
efficacy, safety, and tolerability of a 24-month treatment regimen including delamanid in a child with extensively drug-resistant tuberculosis: a case report and review of the literature.multidrug-resistant (mdr) and extensively drug-resistant (xdr) tuberculosis (tb) are emerging problems in several countries. these infections require long and expensive treatment regimens. recently, 2 new drugs, bedaquiline and delamanid, have been approved in several countries for use in adults with severe, difficult-to-treat mdr-tb, and it has been suggested that they could also be administered to children with mdr-tb and limited treatment options. however, no study has been completed on their ...201627861363
genome scale identification, structural analysis, and classification of periplasmic binding proteins from mycobacterium tuberculosis.periplasmic-binding proteins occupy the periplasmic space of bacteria and are involved in binding and transport of various ions, siderophores, and other diverse types of solutes. these proteins may be associated with membrane transport systems or may help in activation of signal transducers. there is limited information available on mycobacterium tuberculosis (mtb) periplasm-inhabiting proteins. in the present study, we have performed genome-wide identification and functional annotation of perip ...201627858159
the impact of immune disturbances on the failure of antituberculosis treatment.tuberculosis is an infectious disease caused by mycobacterium tuberculosis complex, with an evolution and treatment outcome determined by the interaction between the mycobacterial and human genotypes. various deficiencies of innate immune response starting from the first encounter of m. tuberculosis with lung cells endanger host infection control due to decreased triggering of cellular immune resistance and disturbed humoral immunity. disturbed cell mediated immunity, known as the basic immune r ...201627857518
new/repurposed drugs for pediatric multidrug-resistant tuberculosis: practice-based recommendations.it is estimated that 33,000 children develop multidrug-resistant tuberculosis (mdr-tb) each year. in spite of these numbers, children and adolescents have limited access to the new and repurposed mdr-tb drugs. there is also little clinical guidance for the use of these drugs and for the shorter mdr-tb regimen in the pediatric population. this is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. this review fills ...201627854508
controlled mycobacterium tuberculosis infection in mice under treatment with anti-il-17a or il-17f antibodies, in contrast to tnfα neutralization.antibodies targeting il-17a or its receptor il-17ra show unprecedented efficacy in the treatment of autoimmune diseases such as psoriasis. these therapies, by neutralizing critical mediators of immunity, may increase susceptibility to infections. here, we compared the effect of antibodies neutralizing il-17a, il-17f or tnfα on murine host responses to mycobacterium tuberculosis infection by evaluating lung transcriptomic, microbiological and histological analyses. coinciding with a significant i ...201627853279
marco variants are associated with phagocytosis, pulmonary tuberculosis susceptibility and beijing lineage.macrophage receptor with collagenous structure (marco) has an important role in the phagocytosis of mycobacterium tuberculosis (m. tuberculosis). we hypothesized that marco polymorphisms are associated with phagocytosis, tuberculosis (tb) disease susceptibility and presentation, and infecting lineage. we used a human cellular model to examine how marco genotype mediates the immune response; a case-control study to investigate tuberculosis host genetic susceptibility; and a host-pathogen genetic ...201627853145
structural analysis of the bacterial proteasome activator bpa in complex with the 20s proteasome.mycobacterium tuberculosis harbors proteasomes that recruit substrates for degradation through an ubiquitin-like modification pathway. recently, a non-atpase activator termed bpa (bacterial proteasome activator) was shown to support an alternate proteasomal degradation pathway. here, we present the cryo-electron microscopy (cryo-em) structure of bpa in complex with the 20s core particle (cp). for docking into the cryo-em density, we solved the x-ray structure of bpa, showing that it forms tight ...201627839949
discovery of new chemical entities as potential leads against mycobacterium tuberculosis.a series of biheterocyclic (1h-indole, benzofuran, pyrazolo[1,5-a]pyrimidine, pyrazolo[1,5-a]pyrimidin-5(4h)-one, imidazo[2,1-b]thiazole and pyrazolo[5,1-b]thiazole) derivatives were synthesized and evaluated for their anti-tubercular activities. the imidazo[2,1-b]thiazoles 9a-c and pyrazolo[5,1-b]thiazoles 10a-c exhibited promising anti-tubercular activity in varying degrees. especially, the 2,6-dimethylpyrazolo[5,1-b]thiazole 10a exhibited strong suppressing function against h37ra strain with ...201627839917
design, development of new synthetic methodology, and biological evaluation of substituted quinolines as new anti-tubercular leads.two series of quinoline-based compounds were designed, synthesised and evaluated for anti-tubercular activity against mycobacterium tuberculosis h37rv (atcc 27294 strain). a new method for friedländer quinoline synthesis has been developed in water under the catalytic influence of the brønsted acid surfactant dbsa. among the forty-two compounds tested for anti-tb activity, twenty-three compounds exhibited significant activity against the growth of m. tuberculosis (mic 0.02-6.25μg/ml). in particu ...201627839684
il-21 signaling is essential for optimal host resistance against mycobacterium tuberculosis infection.il-21 is produced predominantly by activated cd4(+) t cells and has pleiotropic effects on immunity via the il-21 receptor (il-21r), a member of the common gamma chain (γc) cytokine receptor family. we show that il-21 signaling plays a crucial role in t cell responses during mycobacterium tuberculosis infection by augmenting cd8(+) t cell priming, promoting t cell accumulation in the lungs, and enhancing t cell cytokine production. in the absence of il-21 signaling, more cd4(+) and cd8(+) t cell ...201627819295
genotyping of mycobacterium tuberculosis isolates from hormozgan province of iran based on 15-locus miru-vntr and spoligotyping.background. considering that hormozgan province in iran (southern part of iran on the persian gulf) is among the areas with high prevalence of mdr-mtb and attracts so many sailors and tourists, genetic diversity of mtb isolates circulating in this part of iran was evaluated. pattern of tb transmission was also examined. methods and material. a total of 38 isolates of mtb were cultured from tb patients from hormozgan province of iran and standard miru-vntr typing and spoligotyping were applied to ...201627819023
functional characterization of pkni-rv2159c interaction in redox homeostasis of mycobacterium tuberculosis.mycobacterium tuberculosis adapts to stress conditions by responding to the signals from its external environment. m. tuberculosis genome encodes 11 eukaryotic like serine/threonine protein kinases (stpk) and their importance in regulating the physiology and virulence of the bacteria are being explored. previous study from our lab identified the m. tuberculosis stpk, pkni interacts with two peroxidase proteins such as rv2159c and rv0148. in this study, we have characterized the biological functi ...201627818650
a hidden active site in the potential drug target mycobacterium tuberculosis dutpase is accessible through small amplitude protein conformational changes.dutpases catalyze the hydrolysis of dutp into dump and pyrophosphate to maintain the proper nucleotide pool for dna metabolism. recent evidence suggests that dutpases may also represent a selective drug target in mycobacteria because of the crucial role of these enzymes in maintaining dna integrity. nucleotide-hydrolyzing enzymes typically harbor a buried ligand-binding pocket at interdomain or intersubunit clefts, facilitating proper solvent shielding for the catalyzed reaction. the mechanism b ...201627815500
typing method for the qub11a locus of mycobacterium tuberculosis: is6110 insertions and tandem repeat analysis.qub11a is used as a locus for variable number of tandem repeats (vntr) analysis of mycobacterium tuberculosis beijing lineage. however, amplification of qub11a occasionally produces large fragments (>1,400 bp) that are not easily measured by capillary electrophoresis because of a lack of the typical stutter peak patterns that are used for counting repeat numbers. is6110 insertion may complicate vntr analysis of large qub11a fragments in m. tuberculosis. we established a method for determining bo ...201627812529
association of mannose-binding lectin polymorphisms with tuberculosis susceptibility among chinese.tuberculosis (tb) is caused by infection of mycobacterium tuberculosis. host genetic variability is an important determinant of the risk of developing tb in humans. although the association between mbl2 polymorphisms and tb has been studied in various populations, the results are controversial. in this study four functional single-nucleotide polymorphisms (snps, h/l, x/y, p/q and a/b) across the mbl2 gene were genotyped by direct dna sequencing of pcr products in a case-control population of chi ...201627812036
prxq b from mycobacterium tuberculosis is a monomeric, thioredoxin-dependent and highly efficient fatty acid hydroperoxide reductase.mycobacterium tuberculosis (m. tuberculosis) is the intracellular bacterium responsible for tuberculosis disease (td). inside the phagosomes of activated macrophages, m. tuberculosis is exposed to cytotoxic hydroperoxides such as hydrogen peroxide, fatty acid hydroperoxides and peroxynitrite. thus, the characterization of the bacterial antioxidant systems could facilitate novel drug developments. in this work, we characterized the product of the gene rv1608c from m. tuberculosis, which according ...201627751911
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