| validation of drug-like inhibitors against mycobacterium tuberculosis l-aspartate α-decarboxylase using nuclear magnetic resonance (1h nmr). | the catalytic activity of l-aspartate α-decarboxylase (adc) is essential for the growth of several micro-organisms, including mycobacterium tuberculosis (mtb), and has triggered efforts for the development of pharmaceutically active compounds against tuberculosis. the present study is a continuation of our recent chemoinformatics-based design approach for identifying potential drug-like inhibitors against mtbadc. we report an nmr-based protocol that allows label-free and direct monitoring of enz ... | 2012 | 23029336 |
| genome-wide expression profiling identifies type 1 interferon response pathways in active tuberculosis. | tuberculosis (tb), caused by mycobacterium tuberculosis (m.tb), remains the leading cause of mortality from a single infectious agent. each year around 9 million individuals newly develop active tb disease, and over 2 billion individuals are latently infected with m.tb worldwide, thus being at risk of developing tb reactivation disease later in life. the underlying mechanisms and pathways of protection against tb in humans, as well as the dynamics of the host response to m.tb infection, are inco ... | 2012 | 23029268 |
| mycobacterium tuberculosis infection and tissue factor expression in macrophages. | a number of earlier studies reported the occurrence of thrombotic complications, particularly disseminated intravascular coagulation and deep vein thrombosis, in tuberculosis (tb) patients. the aberrant expression of tissue factor (tf), the primary activator of coagulation cascade, is known to be responsible for thrombotic disorders in many diseases including bacterial infections. further, expression of tf by cells of the monocyte/macrophage lineage is also shown to contribute to the development ... | 2012 | 23029190 |
| attenuated mycobacterium tuberculosis so2 vaccine candidate is unable to induce cell death. | it has been proposed that mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. as part of the characterization of a novel tuberculosis vaccine candidate, the m. tuberculosis phop mutant so2, we sought to evaluate its potential to induce host cell death. the parental m. tuberculosis mt103 strain and the current vaccine ... | 2012 | 23028853 |
| different patterns of cytokines and chemokines combined with ifn-γ production reflect mycobacterium tuberculosis infection and disease. | ifn-γ is presently the only soluble immunological marker used to help diagnose latent mycobacterium tuberculosis (m.tb) infection. however, ifn-γ is not available to distinguish latent from active tb infection. moreover, extrapulmonary tuberculosis, such as tuberculous pleurisy, cannot be properly diagnosed by ifn-γ release assay. as a result, other disease- or infection-related immunological biomarkers that would be more effective need to be screened and identified. | 2012 | 23028695 |
| global assessment of genomic regions required for growth in mycobacterium tuberculosis. | identifying genomic elements required for viability is central to our understanding of the basic physiology of bacterial pathogens. recently, the combination of high-density mutagenesis and deep sequencing has allowed for the identification of required and conditionally required genes in many bacteria. genes, however, make up only a part of the complex genomes of important bacterial pathogens. here, we use an unbiased analysis to comprehensively identify genomic regions, including genes, domains ... | 2012 | 23028335 |
| modeling phenotypic metabolic adaptations of mycobacterium tuberculosis h37rv under hypoxia. | the ability to adapt to different conditions is key for mycobacterium tuberculosis, the causative agent of tuberculosis (tb), to successfully infect human hosts. adaptations allow the organism to evade the host immune responses during acute infections and persist for an extended period of time during the latent infectious stage. in latently infected individuals, estimated to include one-third of the human population, the organism exists in a variety of metabolic states, which impedes the develop ... | 2012 | 23028286 |
| maintenance of peripheral t cell responses during mycobacterium tuberculosis infection. | fully functional t cells are necessary for the maintenance of protective immunity during chronic infections. however, activated t cells often undergo apoptosis or exhaustion upon chronic stimulation mediated by ag or inflammation. t cell attrition can be compensated for by the production of thymus-derived t cells, although the new naive t cells must undergo t cell priming and differentiation under conditions different from those encountered during acute infection. we used a murine model of mycob ... | 2012 | 23028057 |
| construction of a dna vaccine based on the mycobacterium tuberculosis ag85a/mpt64 fusion gene and evaluation of its immunogenicity. | the aim of this study was to construct a dna vaccine based on the ag85a/mpt64 gene of mycobacterium tuberculosis (mtb) and analyze its immunogenicity by enzyme-linked immunospot (elispot) assay. the fusion gene encoding ag85a/mpt64 was amplified by pcr from the genome of the mtb h37rv strain and cloned into a eukaryotic expression vector followed by confirmation using restriction endonuclease digestion and dna sequencing. the immunogenicity of the recombinant vector was tested in vivo in balb/c ... | 2012 | 23027024 |
| the role of lipid raft aggregation in the infection of type ii pneumocytes by mycobacterium tuberculosis. | dynamic, cholesterol-dense regions of the plasma membrane, known as lipid rafts (lr), have been observed to develop during and may be directly involved in infection of host cells by various pathogens. this study focuses on lr aggregation induced in alveolar epithelial cells during infection with mycobacterium tuberculosis (mtb) bacilli. we report dose- and time-dependent increases in lr aggregation after infection with three different strains at multiplicities of infection of 1, 10 and 100 from ... | 2012 | 23024786 |
| inflammatory signals direct expression of human il12rb1 into multiple distinct isoforms. | il12rb1 is essential for human resistance to multiple intracellular pathogens, including mycobacterium tuberculosis. in its absence, the proinflammatory effects of the extracellular cytokines il-12 and il-23 fail to occur, and intracellular bacterial growth goes unchecked. given the recent observation that mouse leukocytes express more than one isoform from il12rb1, we examined whether primary human leukocytes similarly express more than one isoform from il12rb1. we observed that human leukocyte ... | 2012 | 23024274 |
| trends of anti-tuberculosis drug resistance pattern in new cases and previously treated cases of extrapulmonary tuberculosis cases in referral hospitals in northern india. | drug-resistant tuberculosis is one of major current challenges to global public health. the transmission of resistant strains is increasing as a burden of multidrug-resistant tuberculosis (mdr-tb) patients in extra pulmonary tuberculosis (eptb) cases in india. | 2015 | 23023350 |
| interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease. | this work focuses on the interaction of mycolic acids (mas) and two antimycobacterial compounds (rifabutin and n'-acetyl-rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. for this purpose, accurate biophysical techniques (langmuir isotherms, brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: mas mimic bacterial lipids of the mycobacterium tuberculo ... | 2013 | 23022131 |
| primary anti-tuberculous drugs resistance of pulmonary tuberculosis in southwestern saudi arabia. | the emergence of drug-resistant tuberculosis (tb) is an increasing problem which adversely affects patient care and public health. this study aimed to determine the rates and patterns of primary anti-tb drugs resistance in najran, southwestern saudi arabia. the study included 80 smear-positive new pulmonary tb patients. sputum samples were cultured on lowenstein-jensen and middle-brook 7h10 media. mycobacterium tuberculosis susceptibility testing was done by the conventional agar proportion meth ... | 2012 | 23021650 |
| tuberculous endocarditis. | mycobacterium tuberculosis (tb) is a major cause of death globally. tb is capable of infecting every organ in the body, and the heart is no exception. tuberculous endocarditis (tbe) was first reported in 1892 and subsequently many other cases have been described, highlighting the significant morbidity and mortality associated with this manifestation of tb. tbe usually presents with miliary tuberculosis and most early cases were diagnosed on autopsy. with increasing application of prosthetic valv ... | 2013 | 23021600 |
| anti-tuberculosis drug resistance pattern among pulmonary tuberculosis patients with or without hiv infection in mwanza, tanzania. | anti-tuberculosis drug resistance is a major problem in tuberculosis (tb) control, particularly multi-drug resistance tb (mdr-tb). the objective of this study was to determine the prevalence of primary and acquired anti-tb drug resistance among newly diagnosed pulmonary tb (ptb) and relapse cases. sputa were collected from newly diagnosed and relapse ptb patients. drug susceptibility tests (dst) were performed on sputum culture positive isolates of mycobacterium tuberculosis using resistance rat ... | 2012 | 26591721 |
| naturally acquired mycobacterium tuberculosis complex in laboratory pig-tailed macaques. | here we present a case series from a primate research facility. the index case, a 4-year-old pig-tailed macaque (macaca nemestrina) experimentally infected with chimeric simian-human immunodeficiency virus (shivsf162 p4), developed weight loss and was euthanized. based on necropsy results the animal was diagnosed with opportunistic atypical mycobacteriosis associated with simian aids (saids). subsequently, tissues from the index animal, as well as tissues and oral mucosal swabs from six shiv-inf ... | 2012 | 26038402 |
| ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype. | emerging evidence suggests that mycobacterium tuberculosis (mtb) lineage and host ethnicity can determine tuberculosis (tb) clinical disease patterns but their relative importance and interaction are unknown. | 2013 | 23019255 |
| analysis of mutations in the gyra and gyrb genes and their association with the resistance of mycobacterium tuberculosis to levofloxacin, moxifloxacin and gatifloxacin. | the purpose of the present study was to analyse mutations in the gyra and gyrb genes of mycobacterium tuberculosis and define the possible correlation between these mutations and resistance to levofloxacin (lvx), moxifloxacin (mfx) and gatifloxacin (gat), based on their mics. one hundred and forty-two m. tuberculosis clinical isolates were collected from pulmonary tuberculosis patients in the moscow region. all m. tuberculosis strains were tested for drug susceptibility to rifampicin and isoniaz ... | 2013 | 23019190 |
| role of complement activation and antibody in the interaction between mycobacterium tuberculosis and human macrophages. | mycobacterium tuberculosis-specific antibodies possess immunomodulatory effects during tuberculosis infection. prior sensitization to environmental mycobacteria is known to suppress immune responses against bcg and m. tuberculosis. mycobacteria-induced antibodies can influence events such as complement activation and phagocytosis during infectious process. in the present study role of anti-m. tuberculosis igg (anti-m. tb igg) antibody during interaction between m. tuberculosis and human macropha ... | 2012 | 23016491 |
| evaluation of pseudopteroxazole and pseudopterosin derivatives against mycobacterium tuberculosis and other pathogens. | pseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. new semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the terpene skeleton were synthesized. in order to build structure-activity relationships, a set of 29 new and previously reported compounds was assessed for in vitro antimicrobial and cytotoxic activities. ... | 2012 | 23015770 |
| analysis of immune responses against a wide range of mycobacterium tuberculosis antigens in patients with active pulmonary tuberculosis. | characterizing host immune responses to molecular targets of mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. we investigated the immune response against a large series of m. tuberculosis antigens, including 5 classical and 64 nonclassical (39 dosr regulon-encoded, 4 resuscitation-promoting factor [rpf], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (tb) patients. whole blood from tb patients (n = 34) was stimulated i ... | 2012 | 23015647 |
| reversible and efficient inhibition of udp-galactopyranose mutase by electrophilic, constrained and unsaturated udp-galactitol analogues. | a series of udp-galactitols were designed as analogues of high-energy intermediates of the udp-galactopyranose mutase (ugm) catalyzed furanose/pyranose interconversion, an essential step of mycobacterium tuberculosis cell wall biosynthesis. the final compounds structurally share the udp and the galactitol substructures that were connected by four distinct electrophilic connections (epoxide, lactone and michael acceptors). all molecules were synthesized from a common perbenzylated acyclic galacto ... | 2012 | 23015271 |
| immunotherapy using il-2 and gm-csf is a potential treatment for multidrug-resistant mycobacterium tuberculosis. | this study investigated the therapeutic effects of interleukin (il)-2 and granulocyte-macrophage colony-stimulating factor (gm-csf) co-administrated with antibacterial agents isoniazid (inh) and rifampin (rif) to treat a mouse model of tuberculosis (tb) infection. a drug-susceptible tb strain, h37rv was used to infect mice and the effectiveness of il-2 and gm-csf was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. nex ... | 2012 | 23015129 |
| spolpred: rapid and accurate prediction of mycobacterium tuberculosis spoligotypes from short genomic sequences. | spoligotyping is a well-established genotyping technique based on the presence of unique dna sequences in mycobacterium tuberculosis (mtb), the causal agent of tuberculosis disease (tb). although advances in sequencing technologies are leading to whole-genome bacterial characterization, tens of thousands of isolates have been spoligotyped, giving a global view of mtb strain diversity. to bridge the gap, we have developed spolpred, a software to predict the spoligotype from raw sequence reads. ou ... | 2012 | 23014632 |
| triple valve endocarditis by mycobacterium tuberculosis: a case report. | granulomas caused by mycobacterium tuberculosis have been observed at autopsy in the heart, pre-dominantly in the myocardium and endocardium, but rarely involving the coronary vessels and valvular structures. mycobacterium tuberculosis valvular endocarditis is extremely rare, with most reports coming from autopsy series. | 2012 | 23013220 |
| nonsteroidal anti-inflammatory drug sensitizes mycobacterium tuberculosis to endogenous and exogenous antimicrobials. | existing drugs are slow to eradicate mycobacterium tuberculosis (mtb) in patients and have failed to control tuberculosis globally. one reason may be that host conditions impair mtb's replication, reducing its sensitivity to most antiinfectives. we devised a high-throughput screen for compounds that kill mtb when its replication has been halted by reactive nitrogen intermediates (rnis), acid, hypoxia, and a fatty acid carbon source. at concentrations routinely achieved in human blood, oxyphenbut ... | 2012 | 23012453 |
| acute tuberculous abscess of the thyroid gland. | the authors are presenting our experience of managing an interesting case of a 28-year-old woman who presented to our clinic with a midline neck swelling of 1-month duration. there was a rapid increase in the degree of swelling associated with erythema, pain and fever 7 days before seeking medical help. plain and contrast-enhanced ct scans of the neck were done. diagnosis of acute suppurative abscess was made and the patient underwent emergency incision and drainage. histopathological examinatio ... | 2012 | 23010466 |
| the esx/type vii secretion system modulates development, but not virulence, of the plant pathogen streptomyces scabies. | streptomyces scabies is a model organism for the investigation of plant-microbe interactions in gram-positive bacteria. here, we investigate the type vii protein secretion system (t7ss) in s. scabies; the t7ss is required for the virulence of other gram-positive bacteria, including mycobacterium tuberculosis and staphylococcus aureus. the hallmarks of a functional t7ss are an eccc protein that forms an essential component of the secretion apparatus and two small, sequence-related substrate prote ... | 2013 | 23009676 |
| cost comparison of wirelessly vs. directly observed therapy for adherence confirmation in anti-tuberculosis treatment. | a us clinic treating patients entering the continuation phase of treatment for mycobacterium tuberculosis. | 2012 | 23006834 |
| importance of the genetic diversity within the mycobacterium tuberculosis complex for the development of novel antibiotics and diagnostic tests of drug resistance. | despite being genetically monomorphic, the limited genetic diversity within the mycobacterium tuberculosis complex (mtbc) has practical consequences for molecular methods for drug susceptibility testing and for the use of current antibiotics and those in clinical trials. it renders some representatives of mtbc intrinsically resistant against one or multiple antibiotics and affects the spectrum and consequences of resistance mutations selected for during treatment. moreover, neutral or silent cha ... | 2012 | 23006760 |
| noninvasive determination of 2-[18f]-fluoroisonicotinic acid hydrazide pharmacokinetics by positron emission tomography in mycobacterium tuberculosis-infected mice. | tuberculosis (tb) is a global pandemic requiring sustained therapy to facilitate curing and to prevent the emergence of drug resistance. there are few adequate tools to evaluate drug dynamics within infected tissues in vivo. in this report, we evaluated a fluorinated analog of isoniazid (inh), 2-[(18)f]fluoroisonicotinic acid hydrazide (2-[(18)f]-inh), as a probe for imaging mycobacterium tuberculosis-infected mice by dynamic positron emission tomography (pet). we developed a tail vein catheter ... | 2012 | 23006755 |
| chronic sternum wound infection caused by mycobacterium tuberculosis after cardiac surgery. | the sternum wound infection, caused by mycobacterium tuberculosis after a cardiac surgery, is an extremely rare postoperative complication. it requires a high degree of suspicion for a correct diagnosis. often a successful treatment is impeded by the insidious nature of tuberculosis infection and the time-consuming diagnosis process. we report two cases in which we successfully treated this infection with sternum resection, wound debridement, and antituberculosis medication. | 2012 | 23006691 |
| day zero quantitative mrna analysis as a prognostic marker in pulmonary tuberculosis category ii patients on treatment. | mycobacterium tuberculosis m-rna quantitation in sputum of pulmonary tuberculosis patients before starting supervised treatment was evaluated as a surrogate for response. sputum specimens were collected from 50 patients (dots category ii treatment; 303 specimens, day 0 to fourth month) and 16 controls (non-tubercular lung disorders). microscopy, reverse-transcriptase pcr and dna-pcr were compared with culture using the bactec 460 system. taqman real-time rt-pcr quantitated the mrna levels. rt-pc ... | 2012 | 23005345 |
| upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampin-resistant, rpob mutant mycobacterium tuberculosis. | multidrug-resistant tuberculosis has emerged as a major threat to tuberculosis control. phylogenetically related rifampin-resistant actinomycetes with mutations mapping to clinically dominant mycobacterium tuberculosis mutations in the rpob gene show upregulation of gene networks encoding secondary metabolites. we compared the expressed proteomes and metabolomes of two fully drug-susceptible clinical strains of m. tuberculosis (wild type) to those of their respective rifampin-resistant, rpob mut ... | 2012 | 23002228 |
| a patient with tuberculous peritonitis with very high serum ca 125. | an 88-year-old woman presented with abdominal pain and distension. serum cancer antigen 125 (ca 125) level was very high; however, abdominal ct reveals ascites without definite mass. ascites analysis revealed a lymphocytic exudate with high adenosine deaminase enzyme level, negative stains for bacteria and negative pcr for mycobacterium tuberculosis. presumptive diagnosis for tuberculous peritonitis was made and antituberculous therapy resulted in the resolution of ascites and normalisation of c ... | 2012 | 23001094 |
| rapid point-of-care detection of the tuberculosis pathogen using a blac-specific fluorogenic probe. | early diagnosis of tuberculosis can dramatically reduce both its transmission and the associated death rate. the extremely slow growth rate of the causative pathogen, mycobacterium tuberculosis (mtb), however, makes this challenging at the point of care, particularly in resource-limited settings. here we report the use of blac (an enzyme naturally expressed/secreted by tubercle bacilli) as a marker and the design of blac-specific fluorogenic substrates as probes for mtb detection. these probes s ... | 2012 | 23000993 |
| gold on paper-paper platform for au-nanoprobe tb detection. | tuberculosis (tb) remains one of the most serious infectious diseases in the world and the rate of new cases continues to increase. the development of cheap and simple methodologies capable of identifying tb causing agents belonging to the mycobacterium tuberculosis complex (mtbc), at point-of-need, in particular in resource-poor countries where the main tb epidemics are observed, is of paramount relevance for the timely and effective diagnosis and management of patients. tb molecular diagnostic ... | 2012 | 23000923 |
| mycobacterium tuberculosis surface protein rv0227c contains high activity binding peptides which inhibit cell invasion. | mycobacterium tuberculosis surface proteins involved in target cell invasion may be identified as a strategy for developing subunit-based, chemically-synthesized vaccines. the rv0227c protein was thus selected to assess its role in the invasion and infection of mycobacterium tuberculosis target cells. results revealed rv0227c localization on mycobacterial surface by immunoelectron microscopy and western blot. receptor-ligand assays using 20-mer, non-overlapping peptides covering the complete rv0 ... | 2012 | 23000473 |
| no evidence of association between mbl2a/o polymorphisms and mycobacterium tuberculosis infection in populations from the brazilian amazon region. | the present study investigated the prevalence of the polymorphisms in the exon 1 of the mbl2 gene in patients with tuberculosis at a hospital in northern brazil, which is a regional reference for the treatment of the disease. the study group was composed of 167 patients with tuberculosis, 34 of which had the extra-pulmonary form of the disease, while the other 133 had the pulmonary type. the control group consists of 159 healthy individuals. samples of dna extracted from leucocytes were submitte ... | 2013 | 23000376 |
| 1,3-azoles from ortho-naphthoquinones: synthesis of aryl substituted imidazoles and oxazoles and their potent activity against mycobacterium tuberculosis. | twenty-three naphthoimidazoles and six naphthoxazoles were synthesised and evaluated against susceptible and rifampicin- and isoniazid-resistant strains of mycobacterium tuberculosis. among all the compounds evaluated, fourteen presented mic values in the range of 0.78 to 6.25 μg/ml against susceptible and resistant strains of m. tuberculosis. five structures were solved by x-ray crystallographic analysis. these substances are promising antimycobacterial prototypes. | 2012 | 23000294 |
| unusual optical resolution of all four tryptophan residues in mpt63 protein by phosphorescence spectroscopy: assignment and significance. | mpt63, a secreted protein of unknown function that is specific to mycobacterium tuberculosis and a potential drug target, contains four tryptophan (trp/w) residues located at positions 26, 48, 82, and 129 in the amino acid sequence. all of the four trp residues have been optically resolved by simple inexpensive phosphorescence spectroscopy at 77 k. the protein architecture provides a delicate micro-environment and location of trp residues giving rise to four different (0,0) bands in the phosphor ... | 2012 | 22998652 |
| bacterial mechanisms of reversible protein s-thiolation: structural and mechanistic insights into mycoredoxins. | mycobacteria produce millimolar concentrations of mycothiol (msh) as their major low molecular weight thiol redox buffer. msh-deficient mutants display increased sensitivity towards reactive oxygen, nitrogen and electrophilic species as well as alkylating agents and antibiotics. msh is maintained in its reduced thiol state by the nadph-dependent mycothiol disulphide reductase (mtr). however, the redoxin that uses the msh/mtr/nadph pathway for reduction of msh-mixed protein disulphides, formed du ... | 2012 | 22998128 |
| [a case of pulmonary tuberculosis associated with orbital myositis]. | ocular tuberculosis is rare. we report a case of orbital myositis suspected to be infected with tuberculosis. in january 2008, a 34-year-old man experienced discomfort in the right eye. in may 2008, this patient developed right exophthalmos, diplopia, and pain in the right eye, and he was diagnosed with idiopathic orbital myositis. the patient underwent 2 courses of steroid pulse therapy; after which, the dosage of steroids was reduced. the steroid treatment reduced the eye pain, but his diplopi ... | 2012 | 22993891 |
| chemical composition of hexane extract of citrus aurantifolia and anti-mycobacterium tuberculosis activity of some of its constituents. | the main aim of this study was to isolate and characterize the active compounds from the hexane extract of the fruit peels of citrus aurantiifolia, which showed activity against one sensitive and three monoresistant (isoniazid, streptomycin or ethambutol) strains of mycobacterium tuberculosis h37rv. the active extract was fractionated by column chromatography, yielding the following major compounds: 5-geranyloxypsoralen (1); 5-geranyloxy-7-methoxycoumarin (2); 5,7-dimethoxycoumarin (3); 5-methox ... | 2012 | 22992784 |
| r753q polymorphism inhibits toll-like receptor (tlr) 2 tyrosine phosphorylation, dimerization with tlr6, and recruitment of myeloid differentiation primary response protein 88. | the r753q polymorphism in the toll-il-1 receptor domain of toll-like receptor 2 (tlr2) has been linked to increased incidence of tuberculosis and other infectious diseases, but the mechanisms by which it affects tlr2 functions are unclear. here, we studied the impact of the r753q polymorphism on tlr2 expression, hetero-dimerization with tlr6, tyrosine phosphorylation, and recruitment of myeloid differentiation primary response protein (myd) 88 and myd88 adapter-like (mal). complementation of hek ... | 2012 | 22992740 |
| host gene-encoded severe lung tb: from genes to the potential pathways. | we are reporting that the two-locus genotype -2518 macrophage chemoattractant protein (mcp)-1 gg and -1607 matrix metalloproteinase (mmp)-1 2g/2g promotes the expression of hyperinflammation in response to mycobacterium tuberculosis infection, inducing extensive tissue damage and severe tuberculosis (tb) disease. carriers of this two-locus genotype have a 13-fold higher chance of developing severe disease and 6.5-fold higher chance of developing permanent lesions, and a 3.864-fold higher chance ... | 2012 | 22992722 |
| alcl3 mediated unexpected migration of sulfonyl groups: regioselective synthesis of 7-sulfonyl indoles of potential pharmacological interest. | a conceptually new and straightforward introduction of sulfonyl groups at the c-7 position of an indole ring has been achieved via alcl(3) mediated unexpected regioselective sulfonyl group migration for n-alkyl/aryl/heteroarylsulfonyl indoles affording potential inhibitors of mycobacterium tuberculosis h37rv chorismate mutase. | 2012 | 22990283 |
| mechanism of feedback allosteric inhibition of atp phosphoribosyltransferase. | mtatp-phosphoribosyltransferase catalyzes the first and committed step in l-histidine biosynthesis in mycobacterium tuberculosis and is therefore subjected to allosteric feedback regulation. because of its essentiality, this enzyme is being studied as a potential target for novel anti-infectives. to understand the basis for its regulation, we characterized the allosteric inhibition using gel filtration, steady-state and pre-steady-state kinetics, and the ph dependence of inhibition and binding. ... | 2012 | 22989207 |
| abelson tyrosine kinase controls phagosomal acidification required for killing of mycobacterium tuberculosis in human macrophages. | the mechanisms that regulate the acidification of intracellular compartments are key to host defense against pathogens. in this paper, we demonstrate that abl tyrosine kinase, a master switch for cell growth and trafficking of intracellular organelles, controls the acidification of lysosomes in human macrophages. pharmacological inhibition by imatinib and gene silencing of abelson (abl) tyrosine kinase reduced the lysosomal ph in human macrophages by increasing the transcription and expression o ... | 2012 | 22988030 |
| inferred spoligoforest topology unravels spatially bimodal distribution of mutations in the dr region. | biomarkers of mycobacterium tuberculosis complex (mtbc) mutate over time. among the biomarkers of mtbc, spacer oligonucleotide type (spoligotype) and mycobacterium interspersed repetitive unit (miru) patterns are commonly used to genotype clinical mtbc strains. in this study, we present an evolution model of spoligotype rearrangements using miru patterns to disambiguate the ancestors of spoligotypes. we use a large patient dataset from the united states centers for disease control and prevention ... | 2012 | 22987125 |
| [risk of infection through use of selective immunomodulating drugs for rheumatoid arthritis]. | new drugs for rheumatoid arthritis (ra) have resulted in an improvement in patients' functioning and morbidity, but are linked with increased risk of infections. traditional immunosuppressant drugs are often used in combination with anti-tumour necrosis factor-alpha (tnf-α) inhibitors or anti-cd20 (rituximab). | 2012 | 22986971 |
| thioridazine: an old neuroleptic effective against totally drug resistant tuberculosis. | globally, tuberculosis infections continue to increase their resistance to antibiotics. multidrug resistant tuberculosis infections (mdr tb) have progressed to extensively drug resistance status (xdr tb) and the latter have evolved in some parts of the world to totally drug resistant (tdr tb) infections. mdr tb is difficult to treat successfully, and when therapy is ineffective, a single case can cost almost $500,000. when the infection is xdr tb therapy is mostly unsuccessful and is accompanied ... | 2013 | 22985923 |
| mlva based classification of mycobacterium tuberculosis complex lineages for a robust phylogeographic snapshot of its worldwide molecular diversity. | multiple-locus variable-number tandem repeat analysis (mlva) is useful to establish transmission routes and sources of infections for various microorganisms including mycobacterium tuberculosis complex (mtc). the recently released sitvitweb database contains 12-loci mycobacterial interspersed repetitive units--variable number of tandem dna repeats (miru-vntr) profiles and spoligotype patterns for thousands of mtc strains; it uses miru international types (mit) and spoligotype international types ... | 2012 | 22984400 |
| smear posetive pulmonary tuberculosis (ptb) prevalence amongst patients at agaro teaching health center, south west ethiopia. | world health organization (who) declared tuberculosis as a global emergency because it poses a serious public health threat in different countries especially, in africa. according to who report of 2007, directly observed treatment short course (dots) coverage in ethiopia reached 95 percent of the population; despite this fact the trend of tuberculosis in most of the districts of ethiopia is not known. hence, this study has revealed the trend and determined the overall prevalence of smear positiv ... | 2012 | 22984333 |
| challenging a dogma: antimicrobial susceptibility testing breakpoints for mycobacterium tuberculosis. | the rise in multidrug-resistant tuberculosis makes it increasingly important that antimicrobial susceptibility testing of mycobacterium tuberculosis produce clinically meaningful and technically reproducible results. unfortunately, this is not always the case because mycobacteriology specialists have not followed generally accepted modern principles for the establishment of susceptibility breakpoints for bacterial and fungal pathogens. these principles specifically call for a definition of the m ... | 2012 | 22984314 |
| the c-terminal domain of the virulence factor mgtc is a divergent act domain. | mgtc is a virulence factor of unknown function important for survival inside macrophages in several intracellular bacterial pathogens, including mycobacterium tuberculosis. it is also involved in adaptation to mg(2+) deprivation, but previous work suggested that mgtc is not a mg(2+) transporter. in this study, we demonstrated that the amount of the m. tuberculosis mgtc protein is not significantly increased by mg(2+) deprivation. members of the mgtc protein family share a conserved membrane n-te ... | 2012 | 22984256 |
| the surprising diversity of mycobacterium tuberculosis: change you can believe in. | | 2012 | 22984117 |
| dynamic population changes in mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. | drug-resistant tuberculosis poses a growing challenge to global public health. however, the diversity and dynamics of the bacterial population during acquisition of drug resistance have yet to be carefully examined. | 2012 | 22984115 |
| chip-seq and the complexity of bacterial transcriptional regulation. | transcription factors (tfs) play a central role in regulating gene expression in all bacteria. yet, until recently, studies of tf binding were limited to a small number of factors at a few genomic locations. chromatin immunoprecipitation followed by sequencing enables mapping of binding sites for tfs in a global and high-throughput fashion. the niaid funded tb systems biology project http://www.broadinstitute.org/annotation/tbsysbio/home.html aims to map the binding sites for every transcription ... | 2013 | 22983621 |
| antigen-presenting cells transfected with hsp65 messenger rna fail to treat experimental tuberculosis. | in the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with dna or rna. however, comparative studies suggest that transfecting dendritic cells with messenger rna (mrna) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. in the present study, we evaluated a new therapeutic strategy to fight tuberculosis ... | 2012 | 22983180 |
| factors associated with genotype clustering of mycobacterium tuberculosis isolates in an ethnically diverse region of southern california, united states. | mycobacterium tuberculosis (mtb) isolates with identical genotypes, found in different patients, are most likely the result of recent transmission. mtb strains with closely related genotypes, called clonal complexes, are most likely derived from one another. we examined mtb genotypes from southern california tb patients from 2005 through 2008 to complete the first comprehensive molecular epidemiology analysis of this complicated and ethnically diverse region. mtb genotypes were characterized wit ... | 2012 | 22982156 |
| a comparison of four sputum pre-extraction preparation methods for identifying and characterising mycobacterium tuberculosis using gcxgc-tofms metabolomics. | in many pulmonary diseases, sputum is a valuable sample material for use in disease characterisation and diagnostics. however, due to its high viscosity and uneven consistency (lumpiness), it is difficult to obtain reproducible/repeatable results during compound extraction and analysis. we subsequently investigated and compared four sputum pre-extraction preparation methods using: 1) sputolysin; 2) a combination of n-acetyl-l-cysteine and sodium hydroxide (nalc-naoh); 3) naoh alone, and 4) a sim ... | 2012 | 22982125 |
| impact of cigarette smoking on rates and clinical prognosis of pulmonary tuberculosis in southern mexico. | to examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (tb) and treatment outcomes. | 2013 | 22982014 |
| evaluation of the antimycobacterium activity of the constituents from ocimum basilicum against mycobacterium tuberculosis. | ocimum basilicum belongs to the genus ocimum (lamiaceae). many species of this genus including o. basilicum have been traditionally used for the treatment of a variety of diseases including respiratory diseases and symptoms of tuberculosis. | 2012 | 22982011 |
| the xpert® mtb/rif assay evaluation in south korea, a country with an intermediate tuberculosis burden. | a central hospital laboratory in south korea. | 2012 | 22981162 |
| secondary metabolites from the unripe pulp of persea americana and their antimycobacterial activities. | the fruits of persea americana (avocado) are nowadays used as healthy fruits in the world. bioassay-guided fractionation of the active ethyl acetate soluble fraction has led to the isolation of five new fatty alcohol derivatives, avocadenols a-d (1-4) and avocadoin (5) from the unripe pulp of p. americana, along with 12 known compounds (6-17). these structures were elucidated by spectroscopic analysis. among the isolates, avocadenol a (1), avocadenol b (2), (2r,4r)-1,2,4-trihydroxynonadecane (6) ... | 2012 | 22980888 |
| evaluation of in-house mpt64 real-time pcr for rapid detection of mycobacterium tuberculosis in pulmonary and extra-pulmonary specimens. | | 2012 | 22980585 |
| efferocytosis is an innate antibacterial mechanism. | mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. although apoptosis of m. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. we find that after apoptosis, m. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocy ... | 2012 | 22980326 |
| probing the mycobacterial trehalome with bioorthogonal chemistry. | mycobacteria, including the pathogen mycobacterium tuberculosis, use the non-mammalian disaccharide trehalose as a precursor for essential cell-wall glycolipids and other metabolites. here we describe a strategy for exploiting trehalose metabolic pathways to label glycolipids in mycobacteria with azide-modified trehalose (treaz) analogues. subsequent bioorthogonal ligation with alkyne-functionalized probes enabled detection and visualization of cell-surface glycolipids. characterization of the m ... | 2012 | 22978752 |
| inhalable microparticles containing nitric oxide donors: saying no to intracellular mycobacterium tuberculosis. | although nitric oxide (no) is a bactericidal component of the macrophage's innate response to intracellular infections such as tuberculosis (tb), prolonged inhalation of no gas has little benefit in chemotherapy of tb. the impact of controlled release of no through intracellular delivery of no donors to macrophages infected in vitro with mycobacterium tuberculosis (mtb) was investigated. inhalable microparticles (mp) were prepared by spray-drying. isosorbide mononitrate (ismn), sodium nitropruss ... | 2012 | 22978290 |
| design, synthesis and evaluation of small molecule reactive oxygen species generators as selective mycobacterium tuberculosis inhibitors. | here, we report 5-hydroxy-1,2,3,4,4a,9a-hexahydro-1,4-ethano-9,10-anthraquinone (13), a small molecule generating reactive oxygen species (ros) in ph 7.4 buffer under ambient aerobic conditions that has selective and potent mycobacterium tuberculosis growth inhibitory activity. | 2012 | 22977884 |
| cord factors from atypical mycobacteria (mycobacterium alvei, mycobacterium brumae) stimulate the secretion of some pro-inflammatory cytokines of relevance in tuberculosis. | the ability to induce several cytokines relevant to tuberculosis (tnf-α, il-1β, il-6, il-12p40 and il-23) by cord factor (trehalose dimycolate) from mycobacterium alvei cr-21(t) and mycobacterium brumae cr-270(t) was studied in the cell lines raw 264.7 and thp-1, and compared to the ability of cord factor from mycobacterium tuberculosis h37rv, where this glycolipid appears to be implicated in the pathogenesis of tuberculosis. details of the fine structure of these molecules were obtained by nmr ... | 2012 | 22977091 |
| a dynamic c-terminal segment in the mycobacterium tuberculosis mn/fe r2lox protein can adopt a helical structure with possible functional consequences. | mycobacterium tuberculosis r2-like ligand-binding oxidase (mtr2lox) belongs to a recently discovered group of proteins that are homologous to the ribonucleotide reductase r2 proteins. mtr2lox carries a heterodinuclear mn/fe cofactor and, unlike r2 proteins, a large ligand-binding cavity. a unique tyrosine-valine cross link is also found in the vicinity of the active site. to date, all known structures of r2 and r2lox proteins show a disordered c-terminal segment. here, we present two new crystal ... | 2012 | 22976985 |
| synthesis and chromatography-free purification of pna-peo conjugates for the functionalisation of gold sensors. | peptide nucleic acids (pnas) linked to high molecular weight (mw) poly(ethylene oxide) (peo) derivatives could be useful conjugates for the direct functionalisation of gold surfaces dedicated to surface plasmon resonance (spr)-based dna sensing. however their use is hampered by the difficulty to obtain them through a convenient and economical route. in this work we compared three synthetic strategies to obtain pna-high mw peo conjugates composed of (a) a 15-mer pna sequence as the probe compleme ... | 2012 | 22976467 |
| a case of spinal tuberculosis from the middle ages in transylvania (romania). | case report. | 2012 | 22976345 |
| anthracostenosis associated with exposure to biomass smoke and presence of mycobacterium tuberculosis. | | 2013 | 22974769 |
| assessment of status of rpob gene in fnac samples of tuberculous lymphadenitis by real-time pcr. | introduction. multidrug resistance tuberculosis (mdr tb), the combined resistance of mycobacterium tuberculosis to isoniazid (inh) and rifampin (rfm) is a major public health problem in india as it ranks second among the mdr-tb high burden countries worldwide. who recommends rfm resistance as a "surrogate marker" for detecting mdr. fnac is the most widely used noninvasive investigative technique for tb lymphadenitis. real-time polymerase chain reaction, an extremely versatile technique can be us ... | 2012 | 22973508 |
| comparison of a dna based pcr approach with conventional methods for the detection of mycobacterium tuberculosis in morocco. | worldwide, tuberculosis (tb) is a major public health problem and the rapid diagnosis and appropriate chemotherapy become the first priority and a serious challenge to improve tb treatment. in the objective of early tb diagnosis and rapid detection of mycobacterium tuberculosis (mtb) in the clinical specimens, the utility of the polymerase chain reaction (pcr) using the insertion sequence 6110 "is6110" as target was compared to conventional methods. | 2012 | 22973493 |
| next-generation ion torrent sequencing of drug resistance mutations in mycobacterium tuberculosis strains. | a novel protocol for full-length mycobacterium tuberculosis gene analysis of first- and second-line drug resistance was developed using the ion torrent personal genome machine (pgm). five genes-rpob (rifampin), katg (isoniazid), pnca (pyrazinamide), gyra (ofloxacin/fluoroquinolone), and rrs (aminoglycosides)-were amplified and sequenced, and results were compared to those obtained by genotypic hain line probe assay (lpa) and phenotypic bactec mgit 960 analysis using 26 geographically diverse sou ... | 2012 | 22972833 |
| the diagnostic performance of the genotype mtbdrplus version 2 line probe assay is equivalent to that of the xpert mtb/rif assay. | molecular diagnostics for mycobacterium tuberculosis have recently been endorsed by the world health organization. the xpert mtb/rif assay was endorsed for use on patient material, regardless of smear gradation, while the genotype mtbdrplus (version 1) has been limited for use on smear-positive patient material. in this study, we evaluated the diagnostic performance of the xpert mtb/rif and genotype mtbdrplus (version 2) assays on smear-positive and smear-negative patient specimens submitted to ... | 2012 | 22972826 |
| novel primer-probe sets for detection and identification of mycobacteria by pcr-microarray assay. | a pcr-microarray assay was developed in which pcr primers and hybridization probes were designed for the 16s rrna genes of 16 clinically relevant mycobacteria and for is6110 of mycobacterium tuberculosis. the assay, based on a multiplex pcr followed by hybridization with oligonucleotide probes, was tested against 16 mycobacterium species and 70 clinical samples. | 2012 | 22972818 |
| new susceptibility breakpoints and the regional variability of mic distribution in mycobacterium tuberculosis isolates. | | 2012 | 22972799 |
| sample preparation of mycobacterium tuberculosis extracts for nuclear magnetic resonance metabolomic studies. | mycobacterium tuberculosis is a major cause of mortality in human beings on a global scale. the emergence of both multi- (mdr) and extensively-(xdr) drug-resistant strains threatens to derail current disease control efforts. thus, there is an urgent need to develop drugs and vaccines that are more effective than those currently available. the genome of m. tuberculosis has been known for more than 10 years, yet there are important gaps in our knowledge of gene function and essentiality. many stud ... | 2012 | 22971839 |
| tuberculosis genotyping--united states, 2004-2010. | tuberculosis (tb) genotyping is a laboratory-based genetic analysis of the bacteria that cause tb disease (i.e., any of the organisms in the mycobacterium tuberculosis complex). when combined with epidemiologic data, tb genotyping has sufficient discriminatory power to help find tb cases likely to be in the same chain of transmission or determine that cases are not related. since 2004, >70,000 m. tuberculosis isolates have been genotyped through partnerships between cdc, national genotyping labo ... | 2012 | 22971745 |
| neonatal tuberculosis: an experience that teaches. | this study reports on an experience following contact by a large number of newborn babies with a nurse infected by active tuberculosis (tb). | 2012 | 22958011 |
| amplified mycobacterium tuberculosis direct test for diagnosing tuberculous pleurisy--a diagnostic accuracy study. | the study was designed to investigate the clinical usefulness of amplified mycobacterium tuberculosis direct (amtd) tests for diagnosing tb pleurisy. | 2012 | 22970318 |
| within-subject interlaboratory variability of quantiferon-tb gold in-tube tests. | the quantiferon®-tb gold in-tube test (qft-git) is a viable alternative to the tuberculin skin test (tst) for detecting mycobacterium tuberculosis infection. however, within-subject variability may limit test utility. to assess variability, we compared results from the same subjects when qft-git enzyme-linked immunosorbent assays (elisas) were performed in different laboratories. | 2012 | 22970142 |
| substrate-bound crystal structures reveal features unique to mycobacterium tuberculosis n-acetyl-glucosamine 1-phosphate uridyltransferase and a catalytic mechanism for acetyl transfer. | n-acetyl-glucosamine-1-phosphate uridyltransferase (glmu), a bifunctional enzyme involved in bacterial cell wall synthesis is exclusive to prokaryotes. glmu, now recognized as a promising target to develop new antibacterial drugs, catalyzes two key reactions: acetyl transfer and uridyl transfer at two independent domains. hitherto, we identified glmu from mycobacterium tuberculosis (glmu(mtb)) to be unique in possessing a 30-residue extension at the c terminus. here, we present the crystal struc ... | 2012 | 22969087 |
| allylic thiocyanates as a new class of antitubercular agents. | tb is a global public health emergency in which new drugs are desperately needed. herein we report on the synthesis of a diverse panel of 41 aryl allylic azides, thiocyanates, isothiouronium salts, and n,n'-diacetylisothioureas that were evaluated for their in vitro activity against replicating and non-replicating mycobacterium tuberculosis (mtb) h(37)rv and toxicity to vero cells. we found a selective group of new and promising compounds having good (micromolar) to excellent (sub-micromolar) po ... | 2012 | 22967767 |
| altered fatty acid metabolism due to rifampicin-resistance conferring mutations in the rpob gene of mycobacterium tuberculosis: mapping the potential of pharmaco-metabolomics for global health and personalized medicine. | abstract we investigated the use of gas chromatography mass spectrometry (gc-ms) metabolomics to better characterize rifampicin-resistance by comparing the fatty acid metabolomes of two rpob mutant mycobacterium tuberculosis strains (s522l and s531l) to that of a fully susceptible wild-type parent strain. using the generated gc-ms metabolite data, principal component analysis (pca) showed a clear differentiation between all three sample groups analyzed. we subsequently identified those metabolit ... | 2012 | 22966781 |
| quinolinyl pyrimidines: potent inhibitors of ndh-2 as a novel class of anti-tb agents. | ndh-2 is an essential respiratory enzyme in mycobacterium tuberculosis (mtb), which plays an important role in the physiology of mtb. herein, we present a target-based effort to identify a new structural class of inhibitors for ndh-2. high-throughput screening of the astrazeneca corporate collection resulted in the identification of quinolinyl pyrimidines as the most promising class of ndh-2 inhibitors. structure-activity relationship studies showed improved enzyme inhibition (ic50) against the ... | 2012 | 24900541 |
| crystal structure of nird, the small subunit of the nitrite reductase nirbd from mycobacterium tuberculosis at 2.0 å resolution. | nird is part of the nitrite reductase complex nirbd that catalyses the reduction of nitrite to nh(3) in nitrate assimilation and anaerobic respiration. the crystal structure analysis of nird from mycobacterium tuberculosis shows a double β-sandwich fold. nird is related in three-dimensional structure and sequence to the rieske proteins; however, it does not contain any fe-s cluster or other cofactors that might be involved in electron transfer. a cysteine residue at the protein surface, conserve ... | 2012 | 22965870 |
| gene chip array for differentiation of mycobacterial species and detection of drug resistance. | gene chip array can differentiate isolated mycobacterial strains using various mycobacterium specific probes simultaneously. gene chip array can evaluate drug resistance to isoniazid and rifampin of tuberculosis strains by detecting drug resistance related gene mutation. this technique has great potential for clinical application. we performed a retrospective study to investigate the capability of gene chip array in the rapid differentiation of species and detection of drug resistance in mycobac ... | 2012 | 22964326 |
| mycobacterium tuberculosis meningitis as the first presentation of chronic granulomatous disease. | | 2012 | 22964288 |
| grading of a positive sputum smear and the risk of mycobacterium tuberculosis transmission. | after the diagnosis of a case of tuberculosis (tb), contact tracing is directed by the risk of transmission, for which sputum acid-fast bacilli (afb) staining results are highly relevant. limited data are available on the effect of the degree of acid-fast positivity, of a polymerase chain reaction (pcr) result or of bronchoalveolar lavage (bal) fluid results on the risk of transmission. | 2012 | 22964038 |
| pulmonary tcr γδ t cells induce the early inflammation of granuloma formation by a glycolipid trehalose 6,6'-dimycolate (tdm) isolated from mycobacterium tuberculosis. | we previously showed that formation of pulmonary granulomas in mice in response to a mycobacterial glycolipid, trehalose 6,6'-dimycolate (tdm) is due to the action of tnf-α and not of ifn-γ. however, the mechanisms of formation and maintenance of pulmonary granulomas are not yet clear. the purpose of the present study is to evaluate the mechanisms of granuloma formation by tdm at the early phase. histological analysis showed that inflammatory cells infiltrated the murine pulmonary interstitium o ... | 2012 | 22963130 |
| spontaneous latency in a rabbit model of pulmonary tuberculosis. | mycobacterium tuberculosis (mtb), the causative agent of tuberculosis (tb), is an exquisitely adapted human pathogen capable of surviving for decades in the lungs of immune-competent individuals in the absence of disease. the world health organization estimates that 2 billion people have latent tb infection (ltbi), defined by a positive immunological response to mtb antigens, with no clinical signs of disease. a better understanding of host and pathogen determinants of ltbi and subsequent reacti ... | 2012 | 22960076 |
| astraodoric acids a-d: new lanostane triterpenes from edible mushroom astraeus odoratus and their anti-mycobacterium tuberculosis h37ra and cytotoxic activity. | tuberculosis (tb) is one of the chronic infectious diseases caused by mycobacterium tuberculosis that causes about 2-3 million deaths per year. isoniazid and rifampicin are examples of first line drugs used for tb treatment; however, they are potentially hepatotoxic. more effective and safer drugs are urgently needed, especially from natural products. basidiomycete mushrooms are known as important sources of pharmaceutically active metabolites including an anti-tb agent. in this work, the chemic ... | 2012 | 22957940 |
| prevalence of pulmonary tuberculosis among adults in a rural sub-district of south india. | we conducted a survey to estimate point prevalence of bacteriologically positive pulmonary tb (ptb) in a rural area in south india, implementing tb program dots strategy since 2002. | 2012 | 22956993 |