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rapid emergence of mycobacterium tuberculosis bedaquiline resistance: lessons to avoid repeating past errors. 201728182568
difference in antibody responses to mycobacterium tuberculosis antigens in japanese tuberculosis patients infected with the beijing/non-beijing genotype.the beijing genotype mycobacterium tuberculosis (mtb), notorious for its virulence and predisposition to relapse, could be identified by spoligotyping based on genetic heterogeneity. the plasma samples from 20 cases of beijing and 16 cases of non-beijing mtb infected individuals and 24 healthy controls (hcs) were collected, and antibodies against 11 antigens (rv0679c142asn, rv0679c142lys, ag85b, ag85a, arc, tdm-m, tdm-k, hbha, mdp-1, lam, and tbgl) were measured by elisa. compared to the hcs, th ...201728182078
imidazoles induce reactive oxygen species in mycobacterium tuberculosis which is not associated with cell death.azoles are a class of antimicrobial drugs used clinically to treat yeast and fungal infections. against pathogenic yeast and fungi, azoles act by inhibiting the activity of the cytochrome p450 cyp51, which is involved in the synthesis of a critical component of the yeast and fungal cell membrane. azoles have antibacterial activity, including against mycobacteria, but the basis for this activity is not well-understood. we demonstrated that imidazoles are bactericidal to mycobacterium tuberculosis ...201728180188
prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban tanzania.helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent mycobacterium tuberculosis infection to tuberculosis (tb) disease and alter the clinical presentation of tb. we assessed the prevalence and determined the clinical relevance of helminth co-infection among tb patients and household contact controls in urban tanzania.201728178325
new concepts in understanding latent tuberculosis.mycobacterium tuberculosis (m.tb), the etiologic agent of tuberculosis, is a prominent global health threat because of the enormous reservoir of subclinical latent tuberculosis infection (ltbi). current diagnostic approaches are limited in their ability to predict reactivation risk and ltbi is recalcitrant to antibiotic treatment. the present review summarizes recent advances in our ability to detect, treat and model ltbi as well as our understanding of bacterial physiology during latency.201728177961
performance of a molecular assay to detect mycobacterium tuberculosis complex dna in clinical specimens: multicenter study in brazil.in high tuberculosis (tb) burden countries, there are few data on the performance of new molecular commercialised assays developed locally.201728177043
primary macrophages and j774 cells respond differently to infection with mycobacterium tuberculosis.macrophages play an essential role in the early immune response to mycobacterium tuberculosis and are the cell type preferentially infected in vivo. primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. here we use high-throughput rna-sequencing to analyse transcriptome dynamics of two macrophage models in response to m. tuberculosis infection. ...201728176867
mycobacterium tuberculosis exploits the ppm1a signaling pathway to block host macrophage apoptosis.the ability to suppress host macrophage apoptosis is essential for m. tuberculosis (mtb) to replicate intracellularly while protecting it from antibiotic treatment. we recently described that mtb infection upregulated expression of the host phosphatase ppm1a, which impairs the antibacterial response of macrophages. here we establish ppm1a as a checkpoint target used by mtb to suppress macrophage apoptosis. overproduction of ppm1a suppressed apoptosis of mtb-infected macrophages by a mechanism th ...201728176854
commiphora leptophloeos phytochemical and antimicrobial characterization.commiphora leptophloeos is a plant specie usually known for its medicinal purposes in local communities in northeast brazil. in order to evaluate its therapeutic potential, we aimed to determine the phytochemical and antimicrobial properties of c. leptophloeos extracts. thin layer chromatography (tlc) was able to detect the presence of phenolic compounds, flavonoids and reducing sugars. three phenolic compounds were identified by hplc and described as gallic, chlorogenic and protocatechuic acids ...201728174564
a bioengineered three-dimensional cell culture platform integrated with microfluidics to address antimicrobial resistance in tuberculosis.antimicrobial resistance presents one of the most significant threats to human health, with the emergence of totally drug-resistant organisms. we have combined bioengineering, genetically modified bacteria, longitudinal readouts, and fluidics to develop a transformative platform to address the drug development bottleneck, utilizing mycobacterium tuberculosis as the model organism. we generated microspheres incorporating virulent reporter bacilli, primary human cells, and an extracellular matrix ...201728174307
complex regulation of neutrophil-derived mmp-9 secretion in central nervous system tuberculosis.central nervous system tuberculosis (cns-tb) may be fatal even with treatment. neutrophils are the key mediators of tb immunopathology, and raised csf matrix metalloproteinase-9 (mmp-9) which correlates to neutrophil count in cns-tb is associated with neurological deficit and death. the mechanisms by which neutrophils drive tb-associated cns matrix destruction are not clearly defined.201728173836
fragment profiling approach to inhibitors of the orphan m. tuberculosis p450 cyp144a1.similarity between the ligand binding profiles of enzymes may aid functional characterization and be of greater relevance to inhibitor development than sequence similarity or structural homology. fragment screening is an efficient approach for characterization of the ligand binding profile of an enzyme and has been applied here to study the family of cytochrome p450 enzymes (p450s) expressed by mycobacterium tuberculosis (mtb). the mtb p450s have important roles in bacterial virulence, survival, ...201728169518
unravelling the networks dictating host resistance versus tolerance during pulmonary infections.the appearance of single cell microorganisms on earth dates back to more than 3.5 billion years ago, ultimately leading to the development of multicellular organisms approximately 3 billion years later. the evolutionary burst of species diversity and the "struggle for existence", as proposed by darwin, generated a complex host defense system. host survival during infection in vital organs, such as the lung, requires a delicate balance between host defense, which is essential for the detection an ...201728168323
utility of real-time quantitative polymerase chain reaction in detecting mycobacterium tuberculosis.this study aimed to assess the value of real-time quantitative polymerase chain reaction (rt-qpcr) for the detection of mycobacterium tuberculosis (mtb). samples from 192 patients with suspected mtb were examined by rt-qpcr and an improved löwenstein-jensen (l-j) culture method. to evaluate the diagnostic usefulness of rt-qpcr in detecting mtb, a receiver operating characteristic (roc) curve for rt-qpcr was generated, and the area under the curve (auc) as well as a cutoff value was calculated. u ...201728168192
anthelmintic therapy modifies the systemic and mycobacterial antigen-stimulated cytokine profile in helminth-latent mycobacterium tuberculosis coinfection.helminth infections are known to modulate cytokine responses in latent tuberculosis (ltb). however, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. we measured the systemic and mycobacterial (tb) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with ltb and with or without coexistent strongyloides stercoralis infection before and after anthelmintic therapy. our data reveal that individuals with ltb and c ...201728167672
acquisition of rifampin resistance in pulmonary tuberculosis.mycobacterium tuberculosis strains with spontaneous mutations conferring resistance to rifampin (rif) are exceedingly rare, and fixed drug combinations typically prevent augmentation of resistance to single drugs. fourteen newly diagnosed tuberculosis patients were treated with rif alone for 14 days, and bacterial loads, including mutation frequencies, were determined. a statistical model estimated that 1% of the remaining viable mycobacteria could be rif resistant after 30 days of monotherapy. ...201728167550
the concomitant occurrence of pulmonary tuberculosis with bronchial anthracofibrosis.bronchial anthracofibrosis (baf), diagnosed bronchoscopically, is a clinical entity which is now beginning to emerge from obscurity. this is commonly encountered in elderly females with history of long-standing exposure to biomass fuel smoke in poorly ventilated kitchens. as awareness of baf has increased in recent times, distinct clinicoradiological and bronchoscopic features of the disease have emerged. diagnosis is achieved by visualisation of bluish-black mucosal hyperpigmentation along with ...201728166918
two cases of eyelid tuberculosis - an uncommon presentation of ocular tuberculosis.mycobacterium tuberculosis apart from being the causative agent of pulmonary tuberculosis is also notorious to cause tuberculosis at various sites in the human body and ocular tuberculosis is one of the extra pulmonary manifestations of this organism. the most common presentation of ocular tuberculosis is anterior uveitis or choroiditis caused by hematogenous infection or hypersensitivity after another organ infection. eyelid involvement by tuberculosis is most of the times secondary to orbital ...201728166917
bayesian population structure analysis reveals presence of phylogeographically specific sublineages within previously ill-defined t group of mycobacterium tuberculosis.mycobacterium tuberculosis genetic structure, and evolutionary history have been studied for years by several genotyping approaches, but delineation of a few sublineages remains controversial and needs better characterization. this is particularly the case of t group within lineage 4 (l4) which was first described using spoligotyping to pool together a number of strains with ill-defined signatures. although t strains were not traditionally considered as a real phylogenetic group, they did contai ...201728166309
correction: evaluation of direct colorimetric mtt assay for rapid detection of rifampicin and isoniazid resistance in mycobacterium tuberculosis.[this corrects the article doi: 10.1371/journal.pone.0169188.].201728166294
programmable transcriptional repression in mycobacteria using an orthogonal crispr interference platform.the development of new drug regimens that allow rapid, sterilizing treatment of tuberculosis has been limited by the complexity and time required for genetic manipulations in mycobacterium tuberculosis. crispr interference (crispri) promises to be a robust, easily engineered and scalable platform for regulated gene silencing. however, in m. tuberculosis, the existing streptococcus pyogenes cas9-based crispri system is of limited utility because of relatively poor knockdown efficiency and proteot ...201728165460
oral recombinant human or mouse lactoferrin reduces mycobacterium tuberculosis tdm induced granulomatous lung pathology.trehalose 6'6-dimycolate (tdm) is the most abundant glycolipid on the cell wall of mycobacterium tuberculosis (mtb). tdm is capable of inducing granulomatous pathology in mouse models that resembles those induced by mtb infection. using the acute tdm model, this work investigates the effect of recombinant human and mouse lactoferrin to reduce granulomatous pathology. c57bl/6 mice were injected intravenously with tdm at a dose of 25 μg·mouse(-1). at day 4 and 6, recombinant human or mouse lactofe ...201728165282
aminorifamycins and sporalactams produced in culture by a micromonospora sp. isolated from a northeastern-pacific marine sediment are potent antibiotics.the new ansa macrolide antibiotics 1 to 4 have been isolated from cultures of a micromonospora sp. obtained from a marine sediment. rifamycins 1 and 2 are the first natural ansa macrolides to have a 3-amino substituent. sporalactams a (3) and b (4) are comprised of a heterocylic core 5 and a 14-membered ansa bridge that are both unprecedented. sporalactam b (4) shows selective and potent inhibition of mycobacterium tuberculosis.201728164711
hematospermia in a returned traveler.hematospermia is a common complaint among patients seen in outpatient urology clinics. the differential diagnosis is broad and includes inflammatory, infectious, neoplastic, structural, systemic, and traumatic causes. the most common infectious causes are uropathogens and sexually transmitted infections. however, with increasing global travel, physicians must maintain a high clinical suspicion for pathogens not endemic to their region, including echinococcus, mycobacterium tuberculosis, and schi ...201728163813
experimental animal modelling for tb vaccine development.research for a novel vaccine to prevent tuberculosis is an urgent medical need. the current vaccine, bcg, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. in general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. usually, this reduction is similar to that induced by bcg, although in some cases a weak but significant impr ...201728163168
the risk of global epidemic replacement with drug-resistant mycobacterium tuberculosis strains.multidrug-resistant tuberculosis (mdr-tb) is a threat to tuberculosis (tb) control. to guide tb control, it is essential to understand the extent to which and the circumstances in which mdr-tb will replace drug-susceptible tb (ds-tb) as the dominant phenotype. the issue was examined by assessing evidence from genomics, pharmacokinetics, and epidemiology studies. this evidence was then synthesized into a mathematical model.201728163165
activity of moxifloxacin and linezolid against mycobacterium tuberculosis in combination with potentiator drugs verapamil, timcodar, colistin and sq109.current treatment for tuberculosis (tb) is complicated by the emergence of multidrug resistant tb (mdr-tb). as a result, there is an urgent need for new powerful anti-tb regimens and novel strategies. in this study, we aimed to potentiate a moxifloxacin + linezolid backbone as treatment for mdr-tb with the efflux pump inhibitors verapamil and timcodar as well as with drugs that act on mycobacterial cell wall stability such as colistin and sq109. using a time-kill kinetics assay, the activities o ...201728162983
mycobacterium tuberculosis proteins involved in cell wall lipid biosynthesis improve bcg vaccine efficacy in a murine tb model.advances in tuberculosis (tb) vaccine development are urgently required to enhance global disease management. we evaluated the potential of mycobacterium tuberculosis (m. tb)-derived protein antigens rv0447c, rv2957 and rv2958c to boost bcg vaccine efficacy in the presence or absence of glucopyranosyl lipid adjuvant formulated in a stable emulsion (gla-se) adjuvant.201728161464
safety and efficacy of the c-tb skin test to diagnose mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial.targeted screening and treatment of mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. c-tb (statens serum institute, copenhagen, denmark) is a novel specific skin test based on esat-6 and cfp10 antigens. we investigated the safety and diagnostic potential of c-tb compared with established tests in the contact-tracing setting.201728159608
humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and löfgren's syndrome using high-content peptide microarrays.sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (tb) suggest mycobacterial involvement in its pathogenesis. high-content peptide microarrays (hcpm) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis.201728159576
transmission electron microscopy of xdr mycobacterium tuberculosis isolates grown on high dose of ofloxacin.the aim of the study was to investigate behavior of resistant mycobacterium tuberculosis (mtb) isolates under a high dose of ofloxacin and its morphological changes. 19 extensively drug resistant (xdr) clinical isolates of mtb were grown on löwenstein-jensen medium containing progressively increasing concentrations of ofloxacin (2, 4, 8, 16, 32 mg/l). ultra-structure analyses of resistant isolates grown on ofloxacin were conducted by transmission electron microscopy (tem). fixation was carried out ...201728157163
planarity of benzoylthiocarbazate tuberculostatics. iii. diesters of 3-(2-hydroxybenzoyl)dithiocarbazic acid.searches for new tuberculostatic agents are important considering the occurrence of drug-resistant strains of mycobacterium tuberculosis. the structures of three new potentially tuberculostatic compounds, namely isopropyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, c12h16n2o2s2, (z)-benzyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, c16h16n2o2s2, and dibenzyl (2-hydroxybenzoyl)carbonohydrazonodithioate propan-2-ol monosolvate, c22h20n2o2s2·c3h8o, were determined by x-ray diffract ...201728157125
mycobacterium tuberculosis replicates within necrotic human macrophages.mycobacterium tuberculosis modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication is less characterized. in this study, we investigate the impact of plasma membrane (pm) integrity on bacterial replication in different functional populations of human primary macrophages. we discovered that ifn-γ enhanced bacterial replication in macrophage colony-stimulating factor-differentiated macrophages more than in granulocyte-macrophage colony-stimula ...201728242744
corrigendum to "immunogencity of antigens from mycobacterium tuberculosis self-assembled as particulate vaccines" [int. j. med. microbiol. 306 (2016) 624-632]. 201728242005
immunogenicity and therapeutic effects of a mycobacterium tuberculosis rv2190c dna vaccine in mice.tuberculosis (tb) is a major global public health problem. new treatment methods on tb are urgently demanded. in this study, mycobacterium tuberculosis (mtb) rv2190c dna vaccine was prepared and its immunogenicity and therapeutic effects were evaluated.201728241799
quantitative proteomic and phosphoproteomic analysis of h37ra and h37rv strains of mycobacterium tuberculosis.mycobacterium tuberculosis, the causative agent of tuberculosis, accounts for 1.5 million human deaths annually worldwide. despite efforts to eradicate tuberculosis, it still remains a deadly disease. the two best characterized strains of m. tuberculosis, virulent h37rv and avirulent h37ra, provide a unique platform to investigate biochemical and signaling pathways associated with pathogenicity. to delineate the biomolecular dynamics that may account for pathogenicity and attenuation of virulenc ...201728241730
essentiality of mmpl3 and impact of its silencing on mycobacterium tuberculosis gene expression.mmpl3 is an inner membrane transporter of mycobacterium tuberculosis responsible for the export of trehalose momomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (tdm), as well as mycolic acids bound to arabinogalactan. mmpl3 represents an emerging target for tuberculosis therapy. in this paper, we describe the construction and characterization of an mmpl3 knockdown strain of m. tuberculosis. downregulation of mmpl3 led to a stop in bacterial division and ...201728240248
a systematic review of east african-indian family of mycobacterium tuberculosis in brazil.the mycobacterium tuberculosis east african-indian (eai) spoligotyping family (belonging to lineage 1, indo-oceanic, defined by the region of deletion rd239) is distributed worldwide, but is more prevalent in southeast asia, india, and east africa. studies in latin america have rarely identified eai. in this study, we describe the occurrence of the eai family in brazil.201728238627
passive transfer of interferon-γ over-expressing macrophages enhances resistance of scid mice to mycobacterium tuberculosis infection.infection with mycobacterium tuberculosis (m.tb) is associated with increased deaths worldwide. alveolar macrophages (ams) play a critical role in host defense against infection with this pathogen. in this work we tested the hypothesis that passive transfer of normal ams, ifn-γ activated ams, or macrophages transduced to over-express ifn-γ into the lungs of immunosuppressed scid mice, where resident macrophages are present but not functional, would enhance alveolar immunity and increase clearanc ...201728237876
three year evaluation of xpert mtb/rif in a low prevalence tuberculosis setting: a scottish perspective.xpert mtb/rif (cepheid) is a rapid molecular assay shown to be sensitive and specific for pulmonary tuberculosis (tb) diagnosis in highly endemic countries. we evaluated its diagnostic performance in a low tb prevalence setting, examined rifampicin resistance detection and quantitative capabilities predicting graded auramine microscopy and time to positivity (ttp) of culture.201728237624
recurrent tuberculosis in an urban area in china: relapse or exogenous reinfection?recurrent tuberculosis is an important indicator of the effectiveness of tuberculosis control and can occur by relapse or exogenous reinfection. we conducted a retrospective cohort study on all bacteriologically confirmed tuberculosis cases that were successfully treated between 2000 and 2012 in shanghai, an urban area with a high number but a low prevalence rate of tuberculosis cases and a low prevalence of hiv infection. genotyping the mycobacterium tuberculosis from clinical isolates was used ...201728237039
local targeting nf-κb in the lung tissue of tb-infected mice diminishes the level of pathology.mice of the genetically tb-susceptible strain i/st were infected with ∼100 cfu of mycobacterium tuberculosis strain h37rv, and after week 3 post-infection treated by inhalations of the nbd peptide selectively blocking nf-κb activation pathway. this therapy resulted in a pronounced attenuation of lung pathology and down-regulation of the expression of several genes encoding major inflammatory molecules, but did not diminish the level of mycobacterial multiplication in the lungs.201728237038
machine learning and docking models for mycobacterium tuberculosis topoisomerase i.there is a shortage of compounds that are directed towards new targets apart from those targeted by the fda approved drugs used against mycobacterium tuberculosis. topoisomerase i (mttopo i) is an essential mycobacterial enzyme and a promising target in this regard. however, it suffers from a shortage of known inhibitors. we have previously used computational approaches such as homology modeling and docking to propose 38 fda approved drugs for testing and identified several active molecules. to ...201728237034
sclerotiorin inhibits protein kinase g from mycobacterium tuberculosis and impairs mycobacterial growth in macrophages.as a eukaryotic-like ser/thr protein kinase, mycobacterium tuberculosis virulent effector protein kinase g (pkng) mediates mycobacterial survival by regulating bacterial cell metabolic processes and preventing phagosome-lysosome fusion in host macrophages. targeting pkng is an effective strategy for development of anti-tuberculosis (tb) drugs. in the study, we found that sclerotiorin, derived from marine fungi from the south china sea, exhibited moderately strong inhibitory effects on recombinan ...201728237032
single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant mycobacterium tuberculosis strain.globally, about 4.5% of new tuberculosis (tb) cases are multi-drug-resistant (mdr), i.e. resistant to the two most powerful first-line anti-tb drugs. indeed, 480,000 people developed mdr-tb in 2015 and 190,000 people died because of mdr-tb. the mdr mycobacterium tuberculosis m family, which belongs to the haarlem lineage, is highly prosperous in argentina and capable of building up further drug resistance without impairing its ability to spread. in this study, we sequenced the whole genomes of a ...201728237031
c5ar contributes to the weak th1 profile induced by an outbreak strain of mycobacterium tuberculosis.c5a anaphylatoxin is a component of the complement system involved in the modulation of t-cell polarization. herein we investigated whether c5a receptors, c5ar and c5l2, modulate the cytokine profiles induced by mycobacterium tuberculosis (mtb). we analyzed the impact of both receptors on t helper cell polarization induced by the multidrug resistant outbreak strain named m, which is a poor ifn-γ inducer compared with the laboratory strain h37rv. to this aim, we first blocked c5ar or c5l2 of peri ...201728237029
cholesterol plays a larger role during mycobacterium tuberculosis in vitro dormancy and reactivation than previously suspected.it is known that cholesterol plays a key role for mycobacterium tuberculosis (mtb) adaptation and survival within the host, thus contributing to the establishment of dormancy. it has been extensively demonstrated that fatty acids are the main energy source of mtb during infection and dormancy, and it has been proposed that these molecules are implicated in reactivation of bacilli from a dormant state. we used in vitro models to analyze mtb gene expression during dormancy and reactivation when fa ...201728237027
evaluation of highly conserved hsp65-specific nested pcr primers for diagnosing mycobacterium tuberculosis.to evaluate the sensitivity and specificity of a new nested set of primers designed for the detection of mycobacterium tuberculosis complex targeting a highly conserved heat shock protein gene (hsp65).201728234087
endocrine and metabolic aspects of tuberculosis.endocrine and metabolic derangements are infrequent in patients with tuberculosis, but they are important when they occur. the basis for these abnormalities is complex. while mycobacterium tuberculosis has been described to infect virtually every endocrine gland, the incidence of gland involvement is low, especially in the era of effective antituberculosis therapy. furthermore, endocrine and metabolic abnormalities do not always reflect direct infection of the gland but may result from physiolog ...201728233510
targeting phenotypically tolerant mycobacterium tuberculosis.while the immune system is credited with averting tuberculosis in billions of individuals exposed to mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. in individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of m. tuberculosis. the physiological state of nonreplication in bacteria is associated w ...201728233509
[a preliminary study on the molecular characteristics of d-cycloserine resistance of mycobacterium tuberculosis].objective: to investigate the relationship between d-cycloserine resistance and the gene mutations of alra, ddla and cyca of mycobacterium (m.) tuberculosis, as well as the association between d-cycloserine resistance and spoligotyping genotyping. methods: a total of 145 m. tuberculosis strains were selected from the strain bank. d-cycloserine resistant phenotypes of the strains were determined by the proportion method and the minimal inhibitory concentration was determined by resazurin microtit ...201728231674
siderophore transport by mmpl5-mmps5 protein complex in mycobacterium tuberculosis.iron is an essential metal ion required for the various physiological activities of bacteria. the pathogenic bacteria remain dependent on the host cell for their iron requirements and evolved with specialized scavenging machinery in the form of iron chelating siderophores. mycobacterium tuberculosis has two types of siderophore molecules, mycobactin and carboxymycobactin. these are synthesized inside bacterial cells and need to be transported outside by specialized membrane associated proteins. ...201728231453
genetic diversity, transmission dynamics and drug resistance of mycobacterium tuberculosis in angola.tuberculosis (tb) poses a serious public health problem in angola. no surveillance data on drug resistance is available and nothing is known regarding the genetic diversity and population structure of circulating mycobacterium tuberculosis strains. here, we have genotyped and evaluated drug susceptibility of 89 mycobacterium tuberculosis clinical isolates from luanda. thirty-three different spoligotype profiles corresponding to 24 different shared international types (sit) and 9 orphan profiles ...201728230095
perturbed microrna expression by mycobacterium tuberculosis promotes macrophage polarization leading to pro-survival foam cell.tuberculosis (tb) is one of the prevalent causes of death worldwide, with 95% of these deaths occurring in developing countries, like india. the causative agent, mycobacterium tuberculosis (mtb) has the tenacious ability to circumvent the host's immune system for its own advantage. macrophages are one of the phagocytic cells that are central to immunity against mtb. these are highly plastic cells dependent on the milieu and can showcase m1/m2 polarization. m1 macrophages are bactericidal in acti ...201728228760
characterisation of iunh gene knockout strain from mycobacterium tuberculosis.tuberculosis (tb) is an infectious disease caused mainly by the bacillus mycobacterium tuberculosis. the better understanding of important metabolic pathways from m. tuberculosis can contribute to the development of novel therapeutic and prophylactic strategies to combat tb. nucleoside hydrolase (mtiagu-nh), encoded by iunh gene (rv3393), is an enzyme from purine salvage pathway in m. tuberculosis. mtiagu-nh accepts inosine, adenosine, guanosine, and uridine as substrates, which may point to a p ...201728225907
tuberculosis associated factors caused by mycobacterium tuberculosis of the rdrio genotype.tuberculosis (tb) continues to be a disease that affects many countries around the world, including brazil. recently, a subtype of latin american-mediterranean family strain was identified and characterised by rdrio. the strain has been associated with different characteristics of the disease.201728225901
tuberculosis associated factors caused by mycobacterium tuberculosis of the rdrio genotype.tuberculosis (tb) continues to be a disease that affects many countries around the world, including brazil. recently, a subtype of latin american-mediterranean family strain was identified and characterised by rdrio. the strain has been associated with different characteristics of the disease.201728225895
perceived barriers to adherence to tuberculosis infection control measures among health care workers in the dominican republic.introduction health care workers have an increased risk of infection due to occupational mycobacterium tuberculosis exposure, including multidrug-resistant strains. health care workers' risk of developing tuberculosis is greater than that of the general population, whether in low-, intermediate- or high-incidence countries. adherence to infection control measures (administrative controls, environmental controls, and personal respiratory protection) is essential to reduce risk of disease transmis ...201728225541
antituberculosis drug resistance in pulmonary isolates of mycobacterium tuberculosis, cuba 2012-2014.introduction systematic surveillance of antituberculosis drug resistance allows identification of multidrug-resistant and extensively drug-resistant isolates of mycobacterium tuberculosis. surveillance studies of antituberculosis drug resistance systematically conducted in cuba for over 15 years have revealed low circulation of multidrug-resistant tuberculosis, under 1% in new cases. objective characterize antituberculosis drug resistance in isolates of m. tuberculosis recovered from patients wi ...201728225540
results of xpert(®) mtb/rif implementation in kyrgyzstan.in july 2012, the united states agency for international development (usaid) quality health care project introduced the xpert® mtb/rif assay at the facility level of the primary health care system in kyrgyzstan. this study analysed the results of the implementation of xpert.201728225345
patterns of drug resistance among patients with tuberculous pleural effusion in greece.data on the relationship between pleural tuberculosis (tb) and anti-tuberculosis drug resistance are scarce.201728225341
pattern of first- and second-line drug resistance among pulmonary tuberculosis retreatment cases in pakistan.drug resistance in general, and multidrug-resistant tuberculosis (mdr-tb) in particular, threatens global tuberculosis (tb) control efforts. population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant tb in pakistan.201728225340
latent tuberculous infection in household contacts of multidrug-resistant and newly diagnosed tuberculosis.differences in the prevalence of latent tuberculous infection (ltbi) and tuberculosis (tb) disease among contacts of patients with multidrug-resistant tb (mdr-tb) and drug-susceptible tb are not well understood.201728225339
multiple cytokines for the detection of mycobacterium tuberculosis infection in children with tuberculosis.interferon-gamma (ifn-γ) release assays (igras) play an important role in the diagnosis of mycobacterium tuberculosis infection. however, in children with tuberculosis (tb), some studies have shown increased frequencies of false-negative or indeterminate igra results.201728225337
elucidating the biosynthetic pathways of volatile organic compounds in mycobacterium tuberculosis through a computational approach.microbial volatile organic compounds (vocs) have gained prominence in the recent past for their potential use as disease markers. the discovery of microbial vocs has benefited 'difficult to detect' diseases such as tuberculosis (tb). few of the identified vocs of mycobacterium tuberculosis (mtb) are currently being explored for their diagnostic potential. however, very little is known about the biosynthesis of these small lipophilic molecules. here, we propose putative biosynthetic pathways in m ...201728225105
tuberculosis.essential facts tuberculosis (tb) is an infection caused by a bacterium, mycobacterium tuberculosis. while it can affect any part of the body, only pulmonary tb is infectious. according to the charity tb alert, there were 5,758 cases of tb in the uk in 2015 and 39% of them were in london. this represented a fall from a peak of 8,919 cases in 2011. left untreated, tb is life-threatening, but is usually curable with antibiotics. the sooner it is diagnosed and treated, the better, both for the pers ...201728224849
mycobacterium tuberculosis prolyl oligopeptidase induces in vitro secretion of proinflammatory cytokines by peritoneal macrophages.tuberculosis (tb) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in tb. host-bacterium interaction is a key step to tb establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. we presented, for the first time, the identification, biochemic ...201728223969
secretome prediction of two m. tuberculosis clinical isolates reveals their high antigenic density and potential drug targets.the excreted/secreted (es) proteins play important roles during mycobacterium tuberculosis invasion, virulence, and survival inside the host and they are a major source of immunogenic proteins. however, the molecular complexity of the bacillus cell wall has made difficult the experimental isolation of the total bacterial es proteins. here, we reported the genomes of two beijing genotype m. tuberculosis clinical isolates obtained from patients from vietnam (isolate 46) and south africa (isolate 4 ...201728223967
rational design of adjuvants targeting the c-type lectin mincle.the advances in subunit vaccines development have intensified the search for potent adjuvants, particularly adjuvants inducing cell-mediated immune responses. identification of the c-type lectin mincle as one of the receptors underlying the remarkable immunogenicity of the mycobacterial cell wall, via recognition of trehalose-6,6'-dimycolate (tdm), has opened avenues for the rational design of such molecules. using a combination of chemical synthesis, biological evaluation, molecular dynamics si ...201728223515
mycobacterium tuberculosis proteasome accessory factor a (pafa) can transfer prokaryotic ubiquitin-like protein (pup) between substrates.the protein degradation machinery of mycobacterium tuberculosis includes a proteasome and a ubiquitin-like protein (pup). proteasome accessory factor a (pafa) attaches pup to proteins to target them for degradation by the proteasome. free pup is unstable and never observed in extracts of m. tuberculosis, an observation that led us to hypothesize that pafa may need alternative sources of pup. here, we show that pafa can move pup from one proteasome substrate, inositol 1-phosphate synthetase (ino1 ...201728223451
identification of antibody targets for tuberculosis serology using high-density nucleic acid programmable protein arrays.better and more diverse biomarkers for the development of simple point-of-care tests for active tuberculosis (tb), a clinically heterogeneous disease, are urgently needed. we generated a proteomic mycobacterium tuberculosis (mtb) high-density nucleic acid programmable protein array (hd-nappa) that used a novel multiplexed strategy for expedited high-throughput screening for antibody responses to the mtb proteome. we screened sera from hiv uninfected and coinfected tb patients and controls (n = 1 ...201728223349
functional reconstitution of the mycobacterium tuberculosis long-chain acyl-coa carboxylase from multiple acyl-coa subunits.mycobacterium tuberculosis produces a large number of structurally diverse lipids that have been implicated in the pathogenicity, persistence and antibiotic resistance of this organism. most building blocks involved in the biosynthesis of all these lipids are generated by acyl-coa carboxylases whose subunit composition and physiological roles have not yet been clearly established. inconclusive data in the literature refer to the exact protein composition and substrate specificity of the enzyme c ...201728222482
molecular epidemiology of mycobacterium tuberculosis complex in brussels, 2010-2013.the tuberculosis (tb) incidence rate in brussels-capital region is 3-fold higher than in belgium as a whole. eight years after the realization of initial prospective population-based molecular epidemiology investigations in this region, a similar study over the period 2010-2013 was conducted. tb strains isolated from 945 patients were submitted to genotyping by standardized 24-locus-miru-vntr typing and spoligotyping. the phylogenetic analysis showed that the lam (16.7%) and haarlem (15.7%) bran ...201728222189
mycobacterium tuberculosis transmission among elderly persons, yamagata prefecture, japan, 2009-2015.in many countries with low to moderate tuberculosis (tb) incidence, cases have shifted to elderly persons. it is unclear, however, whether these cases are associated with recent mycobacterium tuberculosis transmission or represent reactivation of past disease. during 2009-2015, we performed a population-based tb investigation in yamagata prefecture, japan, using in-depth contact tracing and 24-loci variable-number tandem-repeat typing optimized for beijing family m. tuberculosis strains. we anal ...201728221133
new mycobacterium tuberculosis complex sublineage, brazzaville, congo.tuberculosis is a leading cause of illness and death in congo. no data are available about the population structure and transmission dynamics of the mycobacterium tuberculosis complex strains prevalent in this central africa country. on the basis of single-nucleotide polymorphisms detected by whole-genome sequencing, we phylogenetically characterized 74 mtbc isolates from brazzaville, the capital of congo. the diversity of the study population was high; most strains belonged to the euro-american ...201728221129
mycobacterium tuberculosis infection among asian elephants in captivity.although awareness of tuberculosis among captive elephants is increasing, antituberculosis therapy for these animals is not standardized. we describe mycobacterium tuberculosis transmission between captive elephants based on whole genome analysis and report a successful combination treatment. infection control protocols and careful monitoring of treatment of captive elephants with tuberculosis are warranted.201728221115
mycobacterium tuberculosis infection in free-roaming wild asian elephant.postmortem examination of a wild asian elephant at rajiv gandhi national park, india, revealed nodular lesions, granulomas with central caseation, and acid-fast bacilli in the lungs. pcr and nucleotide sequencing confirmed the presence of mycobacterium tuberculosis. this study indicates that wild elephants can harbor m. tuberculosis that can become fatal.201728221114
pnca gene mutations associated with pyrazinamide resistance in drug-resistant tuberculosis, south africa and georgia.although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. we found polymorphisms in the pnca gene for 70% of multidrug-resistant and 96% of extensively drug-resistant mycobacterium tuberculosis isolates from south africa and georgia. assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drug-resistant tuberculosis.201728221108
mycobacterium tuberculosis in wild asian elephants, southern india.we tested 3 ild asian elephants (elephas maximus) in southern india and confirmed infection in 3 animals with mycobacterium tuberculosis, an obligate human pathogen, by pcr and genetic sequencing. our results indicate that tuberculosis may be spilling over from humans (reverse zoonosis) and emerging in wild elephants.201728221104
more significance of tb-igra except for the diagnose of tuberculosis.tuberculosis (tb)-interferon gamma release assay (igra) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between tb-igra test results and body's immune cells, disease progression and prognosis, which is explored in this study.201728220979
myd88 in mycobacterium tuberculosis infection.myd88 adaptor protein mediates numerous biologically important signal transduction pathways in innate immunity. myd88 signaling fosters bacterial containment and is necessary to raise an adequate innate and acquired immune response to mycobacterium tuberculosis (mtb). the phagosome is a crucial cellular location not only for mtb replication, but it is also where components of the myddosome and inflammasome are recruited. besides its function as a tlr-adaptor protein, myd88 may help stabilizing c ...201728220253
fumarase deficiency causes protein and metabolite succination and intoxicates mycobacterium tuberculosis.enzymes of central carbon metabolism are essential mediators of mycobacterium tuberculosis (mtb) physiology and pathogenicity, but are often perceived to lack sufficient species selectivity to be pursued as potential drug targets. fumarase (fum) is an enzyme of the canonical tricarboxylic acid cycle and is dispensable in many organisms. transposon mutagenesis studies in mtb, however, indicate that fum is required for optimal growth. here, we report the generation and characterization of a geneti ...201728219662
congenital tuberculosis in an extremely preterm infant conceived after in vitro fertilization: case report.congenital tuberculosis is a rare manifestation of tuberculosis. the diagnosis is often delayed, especially in preterm neonates because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy.201728219359
cd137 is a useful marker for identifying cd4(+) t cell responses to mycobacterium tuberculosis.upregulation of cd137 on recently activated cd8(+) t cells has been used to identify rare viral and tumor antigen-specific t cells from the peripheral blood. we aimed to evaluate the accuracy of cd137 for identifying mycobacterium tuberculosis (mtb)-reactive cd4(+) t cells in the peripheral blood of infected individuals by flow cytometry and to investigate the characteristics of these cd137(+) cd4(+) t cells. we initially enrolled 31 active tuberculosis (tb) patients, 31 individuals with latent ...201728218958
dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy.currently, the major issues in the treatment of osteoarticular tuberculosis (tb) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. the application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (inh)-loaded alginate microparticles was fixed to ti implants via adhesive polydopamin ...201728218329
evaluation of rv0220, rv2958c, rv2994 and rv3347c of mycobacterium tuberculosis for serodiagnosis of tuberculosis.tuberculosis (tb), the leading cause of death among infectious diseases worldwide, is caused by mycobacterium tuberculosis (m. tuberculosis). early accurate diagnosis means earlier prevention, treatment and control of tb. to confirm efficient diagnostic antigens for m. tuberculosis, the serodiagnosis value of four recombinant proteins including rv0220, rv2958c, rv2994 and rv3347c was evaluated in this study. the specificities and sensitivities of four recombinant proteins were determined based o ...201728217905
how to diagnose early 5-azacytidine-induced pneumonitis: a case report.interstitial pneumonitis is a classical complication of many drugs. pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. we report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m(2) for 7 days. one week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 °c. she was placed under broa ...201728217822
chemical shift assignments of ribosomal protein s1 from mycobacterium tuberculosis.rpsa, also known as ribosomal protein s1, is an essential protein required for translation initiation of mrnas when their shine-dalgarno sequence is degenerated (sorensen et al. 1998). in addition, rpsa of mycobacterium tuberculosis (m. tb) is involved in trans-translation, which is an effective system mediated by tmrna-smpb to release stalled ribosomes from mrna in the presence of rare codons (keiler 2008). shi et al. found that poa binds to rpsa of mtb and disrupts the formation of rpsa-tmrna ...201728258550
backbone and side-chain resonance assignments for the tmrna-binding protein, smpb, from mycobacterium tuberculosis.small protein b (smpb) is an essential molecule in trans-translation which is a universal biological pathway for protein synthesis in bacteria. trans-translation can release stalled ribosomes from defective mrnas and target tag-protein fragments for degradation, and then restart protein synthesis. the smpb-tmrna complex coordinating with other components of the trans-translation system, plays vital roles in mycobacterium tuberculosis under both stress conditions and non-replicating conditions. t ...201728258549
evaluation of genexpert mtb/rif for detection of pulmonary tuberculosis at peripheral tuberculosis clinics.tuberculosis is one of the most common infectious diseases in china, while delayed patient finding obstructed disease control, especially for smear-negative patients. the current study was undertaken to evaluate the diagnostic accuracy of genexpert mtb/rif compared with conventional methods in the detection of pulmonary tuberculosis patients. a total of 295 spot sputum samples from confirmed pulmonary tuberculosis patients were evaluated from september 2014 to june 2015. each sample was examined ...201728258004
validation of mycobacterium tuberculosis dihydroneopterin aldolase as a molecular target for anti-tuberculosis drug development.an early step of target validation in antimicrobial drug discovery is to prove that a gene coding for a putative target is essential for pathogen's viability. however, little attention has been paid to demonstrate the causal links between gene essentiality and a particular protein function that will be the focus of a drug discovery effort. this should be considered an important step in target validation since a growing number of proteins are found to exhibit multiple and unrelated tasks. here, w ...201728257847
alternate splicing of transcripts shape macrophage response to mycobacterium tuberculosis infection.transcriptional reprogramming of macrophages upon mycobacterium tuberculosis (mtb) infection is widely studied; however, the significance of alternate splicing (as) in shaping cellular responses to mycobacterial infections is not yet appreciated. alternate splicing can influence transcript stability or structure, function and localization of corresponding proteins thereby altering protein stoichiometry and physiological consequences. using comprehensive analysis of a time-series rna-seq data obt ...201728257432
outbreak of drug-resistant mycobacterium tuberculosis among homeless people in atlanta, georgia, 2008-2015.our objective was to describe and determine the factors contributing to a recent drug-resistant tuberculosis (tb) outbreak in georgia.201728257261
the alr-groel1 operon in mycobacterium tuberculosis: an interplay of multiple regulatory elements.threonylcarbamoyladenosine is a universally conserved essential modification of trna that ensures translational fidelity in cellular milieu. tsad, tsab and tsae are identified as trna-a37-threonylcarbamoyl (t(6)a)-transferase enzymes that have been reconstituted in vitro, in few bacteria recently. however, transcriptional organization and regulation of these genes are not known in any of these organisms. this study describes the intricate architecture of a complex multicistronic alr-groel1 opero ...201728256563
 tuberculosis (tb) continues to cause more deaths worldwide than any other single infectious disease. even though tuberculosis appears to be decreasing in incidence globally for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity and mortality as well as cost. since the advent of rifampicin in the 1960s, and the implementation of standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have been changed the first line regim ...201728256383
breaking the barriers: migrants and tuberculosis.tuberculosis (tb) can represent an important clinical and public health in developing and developed countries. low- and middle-income countries are facing an epidemic which is difficult to address because of the drug-resistance spread and the association of tb with hiv/aids. high-income countries, whose tb incidence has decreased in the last decades, can be involved in new tb epidemic waves owing to social, healthcare, and economic hurdles and challenges. in particular, migrants coming from high ...201728256381
role of the health department in tuberculosis prevention and control-legal and public health considerations.because tuberculosis is caused by an infectious organism that is spread from person to person through the air, public health measures are essential to control the disease. there are three priority strategies for tuberculosis prevention and control in the united states: (i) identifying and treating persons who have tuberculosis disease; (ii) finding persons exposed to infectious tuberculosis patients, evaluating them for mycobacterium tuberculosis infection and disease, and providing subsequent t ...201728256190
humoral responses to rv1733c, rv0081, rv1735c, and rv1737c dosr regulon-encoded proteins of mycobacterium tuberculosis in individuals with latent tuberculosis infection.latent tuberculosis infection (ltbi) is evidence of immunological control of tuberculosis. dormancy survival regulator (dosr) regulon-encoded proteins may have a role in the maintenance of ltbi. t cell responses to rv1733c, rv0081, rv1735c, and rv1737c dosr regulon-encoded proteins were found to be most frequent among household contacts of tb cases from uganda compared to other dosr proteins, but antibody responses were not described. we characterized antibody responses to these proteins in indi ...201728255560
annotated whole-genome shotgun sequence of multidrug-resistant mycobacterium tuberculosis mtb13_m isolated from morocco.here, we describe the annotated genome sequence of mycobacterium tuberculosis mtb13_m. the organism was isolated from a sputum sample in morocco.201728254964
a robust synthesis of functionalized 2h-indazoles via solid state melt reaction (ssmr) and their anti-tubercular activity.a facile and convenient approach has been developed for the synthesis of functionalized indazoles via solid state melt reaction using easily accessible starting materials under catalyst-free conditions. this transformation involves electrocyclization via a conjugated nitrene intermediate obtained under thermal conditions. further anti-tubercular activity screening of the molecules was undertaken, among the compounds 3a-3x screened for in vitro antimycobacterial activity against mycobacterium tub ...201728254485
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