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tuberculous gumma: a forgotten entity in the uk.a 24-year-old immunocompetent pakistani man presented with multiple subcutaneous abscesses that had developed and persisted over 2 months. after surgical incision and drainage, mycobacterium tuberculosis was isolated (mtb). further investigation yielded positive sputum cultures confirming pulmonary tuberculosis (tb) too. the patient was started on standard quadruple therapy for disseminated haematogenous tb in the form of tuberculous gumma and pulmonary tb.201324072828
persister populations of mycobacterium tuberculosis in sputum that grow in liquid but not on solid culture media.can the characteristics of persisters in cultures of mycobacterium tuberculosis also be found in bacilli from the sputum of pulmonary tuberculosis patients? the objective of this study was to explore whether the ability of persisters to grow in liquid but not on solid culture media, as in 100 day static cultures, can also be found in bacilli in sputum.201424072170
mutation rate and the emergence of drug resistance in mycobacterium tuberculosis.the emergence and spread of multidrug-resistant strains of mycobacterium tuberculosis remains a major concern of tuberculosis control programmes worldwide, as treatment depends on low-efficacy, toxic compounds that often lead to poor outcomes. m. tuberculosis develops drug resistance exclusively through chromosomal mutations, in particular single-nucleotide polymorphisms. moreover, in laboratory assays the organism exhibits a spontaneous mutation rate that is at the lower end of the bacterial sp ...201424072169
chemical constituents from the roots of ranunculus ternatus and their inhibitory effects on mycobacterium tuberculosis.two new benzophenones, methyl (r)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxyphenyl]-2-hydroxypropanoate (1) and n-butyl (r)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxyphenyl]-2-hydroxypropanoate (2), were isolated from the roots of ranunculus ternatus along with the two known compounds vanillic acid (3) and gallic acid (4). their structures were elucidated by physical and spectroscopic analysis. in addition, compound 1 exhibited obvious activity against tuberculosis, while the activity of a 1:1 mix ...201324071991
complex genetics of drug resistance in mycobacterium tuberculosis.three new studies have used whole-genome sequencing of m. tuberculosis to demonstrate unexpected complexity in the modern evolution of drug-resistant tuberculosis, and a fourth study suggests a close evolutionary relationship between the pathogen and its human host over a period of 70,000 years. collectively, the observations in these studies suggest that future strategies to tackle drug-resistant tuberculosis must integrate host genetics with detailed strain epidemiology.201324071843
laboratory investigations on the diagnosis of tuberculosis in the malnourished tribal population of melghat, india.malnutrition is a major risk factor for the development of tuberculosis (tb). in india, melghat is among the tribal regions which consist of highest number of malnutrition cases. because of the paucity of tb data from these malnourished areas there is an urgent need for the development and evaluation of improved tb diagnostic tests. in the present study, three in house developed diagnostic tests namely tb-ag(antigen) elisa, adenosine deaminase (ada) estimation and is6110 polymerase chain reactio ...201324069327
alterations in the peripheral blood b cell subpopulations of multidrug-resistant tuberculosis patients.the function of b cells in the immune response against mycobacterium tuberculosis (mtb) is still regarded as secondary, although major findings in mouse models of tuberculosis (tb) support their participation as regulators and antibody producers. however, studies in cohorts of tb or multidrug-resistant tb (mdr-tb) patients have failed to clearly identify changes in the circulating b cell pool. therefore, in the present study we aimed at identifying alterations in the different b cell subpopulati ...201424068613
comparison of heat inactivation and cell disruption protocols for identification of mycobacteria from solid culture media by use of vitek matrix-assisted laser desorption ionization-time of flight mass spectrometry.two novel protocols for inactivation and extraction were developed and used to identify 107 mycobacterium clinical isolates, including mycobacterium tuberculosis complex, from solid cultures using vitek matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry. the protocol using heat inactivation with sonication and cell disruption with glass beads resulted in 82.2% and 88.8% species and genus level identifications, respectively.201324068013
mycobacterium tuberculosis outbreak strain of danish origin spreading at worrying rates among greenland-born persons in denmark and greenland.transmission of mycobacterium tuberculosis continues at high rates among greenland-born persons in greenland and denmark, with 203 and 450 notified cases per 10(5) population, respectively, in the year 2010. here, we document that the predominant m. tuberculosis outbreak strain c2/1112-15 of danish origin has been transmitted to greenland-born persons in denmark and subsequently to greenland, where it is spreading at worrying rates and adding to the already heavy tuberculosis burden in this popu ...201324068008
rifampin heteroresistance in mycobacterium tuberculosis cultures as detected by phenotypic and genotypic drug susceptibility test methods.tuberculosis patients may harbor both drug-susceptible and -resistant bacteria, i.e., heteroresistance. we used mixtures of rifampin-resistant and -susceptible mycobacterium tuberculosis strains to simulate heteroresistance in patient samples. molecular tests can be used for earlier discovery of multidrug resistance (mdr), but the sensitivity to detect heteroresistance is unknown. conventional phenotypic drug susceptibility testing was the most sensitive, whereas two line probe assays and sequen ...201324068005
performance monitoring of mycobacterium tuberculosis dried culture spots for use with the genexpert system within a national program in south africa.the use of dried culture spots (dcss) has been reported in the verification of genexpert instruments as being "fit for purpose" for the south african national implementation program. we investigated and compared the performance of the dcss for verification across different bulk batches, testing the settings and cadre of staff, and the xpert mtb/rif assay version. four bulk batches (v005 to v008) were used to prepare (i) 619 dcs panels for laboratory testing on g3 or g4 cartridges by a technologi ...201324068004
the myd88 rs6853 and tirap rs8177374 polymorphic sites are associated with resistance to human pulmonary tuberculosis.toll-like receptors recognize several components of mycobacterium tuberculosis, the main causative agent of tuberculosis. the signaling pathways leading to activation of the immune response require the myd88 and tirap genes. the hypothesis that polymorphic variants of these genes influenced resistance to pulmonary tuberculosis was tested by a case-control study (400 cases and 400 controls). heterozygosity at the polymorphic sites myd88 rs6853 (alleles: a, g) or tirap rs8177374 (s180l) (alleles: ...201324067789
iron acquisition by mycobacterium tuberculosis residing within myeloid dendritic cells.the pathophysiology of mycobacterium tuberculosis (m.tb) infection is linked to the ability of the organism to grow within macrophages. lung myeloid dendritic cells are a newly recognized reservoir of m.tb during infection. iron (fe) acquisition is critical for m.tb growth. in vivo, extracellular fe is chelated to transferrin (tf) and lactoferrin (lf). we previously reported that m.tb replicating in human monocyte-dervied macrophages (mdm) can acquire fe bound to tf, lf, and citrate, as well as ...201324067451
sinomenine suppresses osteoclast formation and mycobacterium tuberculosis h37ra-induced bone loss by modulating rankl signaling pathways.receptor activator of nf-κb ligand (rankl) is essential for osteoclastogenesis. targeting rankl signaling pathways has been an encouraging strategy for treating lytic bone diseases such as osteoporosis and rheumatoid arthritis (ra). sinomenine (sin), derived from chinese medicinal plant sinomenioumacutum, is an active compound to treat ra, but its effect on osteoclasts has been hitherto unknown. in the present study, sin was found to ameliorate m. tuberculosis h37ra (mt)-induced bone loss in rat ...201324066131
the sensitivity of an interferon-γ release assay in microbiologically confirmed pediatric tuberculosis.this study aimed at determining the sensitivity of a whole blood interferon-γ release assay (igra) among children with microbiologically confirmed tuberculosis in a high-burden country. children with a diagnosis of tuberculosis based on clinical and radiographic assessment were tested with an igra in addition to microbiologic examination of appropriate specimens for acid-fast bacilli, mycobacterial rrna, and observation for growth of mycobacterium tuberculosis on appropriate culture media. of th ...201424065457
evaluation of multiplex polymerase chain reaction utilising multiple targets in mycobacterium tuberculosis direct test negative but culture positive cases: a potential method for enhancing the diagnosis of tuberculosis.to evaluate multiplex polymerase chain reaction (mpcr) utilising multiple targets (is6110, protein b [pab] and mpb64 genes) in mycobacterium tuberculosis direct test (mtd) negative but culture positive cases and comparison of mpcr with real-time polymerase chain reaction (rt-pcr) for diagnosis of tuberculosis.201324064644
diagnostic appraisal of simultaneous application of two nested pcrs targeting mpb64 gene and is6110 region for rapid detection of m. tuberculosis genome in culture proven clinical specimens.early diagnosis of tuberculosis is critical for its effective management and prevention. several gene amplification methods are used in the detection of tubercle bacilli from clinical specimens. mpb64 gene and is6110 region have been identified as potential gene targets for the specific detection of mycobacterium tuberculosis from direct clinical specimens.201324064643
construction of some new bioactive building block of thiazolidines.an efficient route for the synthesis of new series of n-[3-(1h-1,2,3-benzotriazol-1-yl)-propyl]-2-(substituted phenyl)-4-oxo-5-(substituted benzylidene)-1,3-thiazolidine-carboxamide has been devised; compounds 5a-j have been synthesized and characterized by ir, 1h nmr, 13c nmr, fab-ms and chemical elemental analysis. all final compounds were screened for their antimicrobial activity against some selected bacteria and fungi and antituberculosis study against mycobacterium tuberculosis and antiinf ...201224061320
in vitro susceptibility of mycobacterium tuberculosis to trimethoprim and sulfonamides in france.five type strains and 55 mycobacterium tuberculosis complex clinical isolates were found resistant to trimethoprim with a mic of >200 mg/liter and susceptible to both sulfadiazine and cotrimoxazole with a mic90 of 10 mg/liter. two m. canettii isolates uniquely yielded silent mutations c156 → t and g238 → c in the folp1 gene. combined with scarce published data, these data indicate that sulfamides could be considered alternative antituberculous antibiotics.201324060877
can inhibitor-resistant substitutions in the mycobacterium tuberculosis β-lactamase blac lead to clavulanate resistance?: a biochemical rationale for the use of β-lactam-β-lactamase inhibitor combinations.the current emergence of multidrug-resistant (mdr) and extensively drug-resistant (xdr) tuberculosis calls for novel treatment strategies. recently, blac, the principal β-lactamase of mycobacterium tuberculosis, was recognized as a potential therapeutic target. the combination of meropenem and clavulanic acid, which inhibits blac, was found to be effective against even extensively drug-resistant m. tuberculosis strains when tested in vitro. yet there is significant concern that drug resistance a ...201324060876
[papilledema secondary to tuberculous meningitis in a patient with type 1 diabetes mellitus].the case is presented of a 29-year-old woman who complained of headache over a period of several days, with loss of visual acuity and pain in her left eye. she had a 3-year history of type 1 diabetes mellitus, and was an immigrant from ecuador. the funduscopic examination revealed a papilledema. the polymerase chain reaction (pcr) study of the cerebrospinal fluid was positive for mycobacterium tuberculosis (mtb). she showed a marked improvement after treatment with anti-tb drugs.201324060305
[study on immunogenicity elicited by a recombinant vaccine of rbcg-rv3133c to fight against dormancy mycobacterium tuberculosis].to obtain a vaccine to defend from dormancy mycobacterium tuberculosis, we constructed the recombinant bacilli calmette-guérin (bcg) vaccine with rv3133c encoding dormancy-correlated transcriptional regulatory protein dosr in mycobacterium tuberculosis as a target gene, and evaluated its immunogenicity in balb/c mice. in this study, we constructed the recombinant plasmids of rpmv361-rv3133c using gene colon technology. we then transformed bcg strains with above-mentioned plasmids to obtain recom ...201324059063
the conservation and application of three hypothetical protein coding gene for direct detection of mycobacterium tuberculosis in sputum specimens.accurate and early diagnosis of tuberculosis (tb) is of major importance in the control of tb. one of the most important technical advances in diagnosis of tuberculosis is the development of nucleic acid amplification (naa) tests. however, the choice of the target sequence remains controversial in naa tests. recently, interesting alternatives have been found in hypothetical protein coding sequences from mycobacterial genome.201324058507
integrated gene co-expression network analysis in the growth phase of mycobacterium tuberculosis reveals new potential drug targets.we have carried out weighted gene co-expression network analysis of mycobacterium tuberculosis to gain insights into gene expression architecture during log phase growth. the differentially expressed genes between at least one pair of 11 different m. tuberculosis strains as source of biological variability were used for co-expression network analysis. this data included genes with highest coefficient of variation in expression. five distinct modules were identified using topological overlap base ...201324056838
systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in mycobacterium tuberculosis.improving our understanding of the relationship between the genotype and the drug resistance phenotype of mycobacterium tuberculosis will aid the development of more accurate molecular diagnostics for drug-resistant tuberculosis. studies that use direct genetic manipulation to identify the mutations that cause m. tuberculosis drug resistance are superior to associational studies in elucidating an individual mutation's contribution to the drug resistance phenotype.201424055765
differential expression of alpha ii spectrin in monocytes of tuberculosis patients.monocytes play a crucial role in immune response to tuberculosis. the present study focuses on identifying differences in the monocyte proteome profile of tuberculosis patients, household contacts and healthy controls. differential protein expression was studied by two-dimensional (2d) gel electrophoresis. one of the spots consistently showed either lower intensity or was absent in patients and was identified as alpha ii-spectrin. the decreased expression of αii-spectrin was further validated by ...201324055022
autophagy meets phagocytosis.autophagy can degrade intracellular bacteria, but how this pathway contributes to phagocytosis is unclear. in this issue of immunity, bonilla et al. (2013) demonstrate an additional role for autophagy in mycobacterium tuberculosis internalization by macrophages.201324054324
interferon-γ responses to mycobacterium tuberculosis rpf proteins in contact investigation.mycobacterium tuberculosis resuscitation-promoting factor proteins (rpf) induce stronger t-cell responses in latently infected individuals (ltbi) than in pulmonary tuberculosis patients (ptb), but there are scarce data concerning the responses to rpf among ltbi with different contact levels. we therefore enrolled ltbi individuals infected through household contacts with ptb as well as people with community exposure who were determined to be ltbi through interferon-γ (ifn-γ) release assays (igras ...201324053975
high clustering rates of multidrug-resistant mycobacterium tuberculosis genotypes in panama.tuberculosis continues to be one of the leading causes of death worldwide and in the american region. although multidrug-resistant tuberculosis (mdr-tb) remains a threat to tb control in panama, few studies have focused in typing mdr-tb strains. the aim of our study was to characterize mdr mycobacterium tuberculosis clinical isolates using pcr-based genetic markers.201324053690
variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a mexican population.the control of mycobacterium tuberculosis (mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (tlrs) and other pattern recognition receptors. our objective was to determine the influence of tlrs polymorphisms in the susceptibility to develop tuberculosis (tb) in amerindian individuals from a rural area of oaxaca, mexico with high tb incidence.201324053111
is6110-based differentiation of mycobacterium tuberculosis strains.in this study, 62 mycobacterium tuberculosis strains were characterized by fast ligation-mediated pcr (flip) and, previously performed, is6110 restriction fragment length polymorphism (rflp). flip proved a reproducible and specific method for differentiation between m. tuberculosis strains. the discriminatory power of flip was close to that of the reference is6110 rflp suggesting its usefulness in studying the genetic diversity of m. tuberculosis strains.201324053024
bead capture increases the sensitivity of sputum microscopy for the diagnosis of tuberculosis in beijing, china.a review of the scientific literature concluded that indirect smear can improve detection of tb in sputum compared to direct smear. however few laboratories have access to centrifugation in order to perform indirect smear. this study investigated whether an alternative method of magnetic bead concentration could enhance diagnosis of tb in china in laboratories which only perform direct smear microscopy.201324052595
mortality among hiv/aids patients coinfected with mycobacterium tuberculosis in southern thailand.the purpose of this study was to investigate the mortality rate among hiv/aids patients coinfected with mycobacterium tuberculosis in southern thailand. a prospective, hospital-based cohort study was conducted among 52,459 hiv/aids patients registered at hospitals in 14 provinces of southern thailand between january 1990 and april 2010. twenty-seven point nine percent of the subjects were coinfected with mycobacterium tuberculosis. coinfection with mycobacterium tuberculosis was not significantl ...201324050098
detection of heteroresistant mycobacterium tuberculosis by pyrosequencing.the ability of pyrosequencing to detect a resistant minority population of a heteroresistant mycobacterium tuberculosis strain was investigated by performing a titration study. a mutant signal was noted only when the proportion of mutant dna in the dna target was 35 to 50%, showing that the sensitivity is significantly lower than that of phenotypic drug susceptibility test methods.201324048543
[recent progress in the genotyping studies of mycobacterium tuberculosis]. 201324047816
[establishment of a mycobacterium tuberculosis proteasome inhibitor model in vitro].to establish a model for screening mycobacterium tuberculosis (m. tuberculosis) proteasome inhibitors in vitro.201324047812
[effects of different cytokines on proliferation and apoptosis of pleural mesothelial cells in human mycobacterium tuberculosis infection].to investigate the effects of different cytokines (il-22, il-17, ifn-γ) on proliferation and apoptosis of human pleural mesothelial cells (pmc) during mycobacterium tuberculosis infection.201324047807
primary multidrug-resistant mycobacterium tuberculosis in 2 regions, eastern siberia, russian federation.of 235 mycobacterium tuberculosis isolates from patients who had not received tuberculosis treatment in the irkutsk oblast and the sakha republic (yakutia), eastern siberia, 61 (26%) were multidrug resistant. a novel strain, s 256, clustered among these isolates and carried eis-related kanamycin resistance, indicating a need for locally informed diagnosis and treatment strategies.201324047678
antimycobacterial activity of cyclic dipeptides isolated from bacillus sp. n strain associated with entomopathogenic nematode.tuberculosis (tb) is one of the leading causes of morbidity and mortality with a global mortality rate of two million deaths per year; one-third of the world's population is infected with mycobacterium tuberculosis.201424047443
s100a8/a9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis.a hallmark of pulmonary tuberculosis (tb) is the formation of granulomas. however, the immune factors that drive the formation of a protective granuloma during latent tb, and the factors that drive the formation of inflammatory granulomas during active tb, are not well defined.201324047412
antibacterial activity of and resistance to small molecule inhibitors of the clpp peptidase.there is rapidly mounting evidence that intracellular proteases in bacteria are compelling targets for antibacterial drugs. multiple reports suggest that the human pathogen mycobacterium tuberculosis and other actinobacteria may be particularly sensitive to small molecules that perturb the activities of self-compartmentalized peptidases, which catalyze intracellular protein turnover as components of atp-dependent proteolytic machines. here, we report chemical syntheses and evaluations of structu ...201324047344
late onset mycobacterium tuberculosis infection after total knee arthroplasty: a systematic review and pooled analysis.mycobacterium tuberculosis (tb) is a rare cause of prosthetic joint infection. the purpose of this study was to provide an evidence-based summarization of the outcomes of tb infection after total knee arthroplasty (tka) with a pooled analysis of the reported cases.201324047227
magnitude of gene mutations conferring drug resistance in mycobacterium tuberculosis isolates from lymph node aspirates in ethiopia.resistance to drugs is due to particular genomic mutations in the specific genes of mycobacterium tuberculosis. timely genetic characterization will allow identification of resistance mutations that will optimize an effective antibiotic treatment regimen. we determine the magnitude of gene mutations conferring resistance to isoniazid (inh), rifampicin (rmp) and ethambutol (emb) among tuberculosis (tb) lymphadenitis patients.201324046537
male tuberculous mastitis: a rare entity.a 28-year old male presented to our clinic complaining of a recent onset of a painful right breast lump with redness and nipple discharge. fine-needle aspiration biopsy revealed caseating granulomas, with a culture positive for mycobacterium tuberculosis. he was found to have a positive ppd, but no other site of pulmonary or extra-pulmonary tuberculosis was identified. treatment with anti-tuberculous drugs lead to complete clinical resolution of the breast lesion. the breast is a rare site of ex ...201324045526
synthesis, characterization and in vitro biological evaluation of some novel 1,3,5-triazine-schiff base conjugates as potential antimycobacterial agents.a series of some novel 1,3,5-triazine-schiff base conjugates (1-32) have been synthesized and evaluated for their in vitro antimycobacterial activity against mycobacterium tuberculosis h37rv using alamar blue assay and the activity expressed as the minimum inhibitory concentration (mic) in μg/ml. compounds 4 (4-methoxy-6-methyl-n-(3,4,5-trimethoxybenzylidene)-1,3,5-triazin-2-amine), 11 (4-methoxy-6-methyl-n-(2-hydroxy-3-bromo-5-chloro-benzylidene)-1,3,5-triazin-2-amine) and 24 (4-methoxy-6-methy ...201324044875
[usefulness of thoracoscopy under local anesthesia in the diagnosis of tuberculous pleurisy occurring during infliximab administration: a case report].we report the case of a 71-year-old man with rheumatoid arthritis. infliximab administration was started as treatment for rheumatoid arthritis in january 2009. as he showed a positive result for the tuberculin test, he was treated with isoniazid for 9 months. he was subsequently referred to our department in october 2011 with a right-sided pleural effusion. when thoracoscopy was performed under local anesthesia, white and red protruding lesions of various sizes were observed in the pleural cavit ...201324044168
[a case of miliary tuberculosis complicated by a tuberculous aneurysm of the thoracic aorta].an 85-year-old woman was admitted to our hospital with the chief complaint of fever. antibiotics were not effective and a chest computed tomography scan revealed a diffuse micronodular shadow and thoracic aortic aneurysm. subsequently, a bronchoscopy sputum culture was positive for mycobacterium tuberculosis. two months after the initiation of chemotherapy, the thoracic aortic aneurysm enlarged despite the improvement in lung findings. tuberculous aneurysms are quite rare, but can be critical an ...201324044167
[clinical experience using rifabutin for treating infection with mycobacterium tuberculosis in elderly japanese patients].to clarify whether rifabutin (rbt) can be used for treating tuberculosis in elderly japanese patients in the clinical setting.201324044166
common recognition principles across diverse sequence and structural families of sialic acid binding proteins.sialic acids form a large family of 9-carbon monosaccharides and are integral components of glycoconjugates. they are known to bind to a wide range of receptors belonging to diverse sequence families and fold classes and are key mediators in a plethora of cellular processes. thus, it is of great interest to understand the features that give rise to such a recognition capability. structural analyses using a non-redundant data set of known sialic acid binding proteins was carried out, which includ ...201424043392
pott's paraplegia secondary to scrofuloderma is a rare association.spinal tuberculosis as all other osteoarticular tuberculosis occurs as a result of hematogenous dissemination of mycobacterium tuberculosis from a primarily infected visceral focus mainly lungs, but pott's paraplegia occurring secondarily to scrofuloderma has not been reported till date.201324042993
thioridazine pharmacokinetic-pharmacodynamic parameters "wobble" during treatment of tuberculosis: a theoretical basis for shorter-duration curative monotherapy with congeners.phenothiazines are being repurposed for treatment of tuberculosis. we examined time-kill curves of thioridazine and first-line drugs against log-growth-phase and semidormant bacilli under acidic conditions and nonreplicating persistent mycobacterium tuberculosis. while both the potency and the efficacy of first-line drugs declined dramatically as m. tuberculosis replication rates decreased, those of thioridazine improved. the mutation prevalence to 3 times the thioridazine mic was <1 × 10(-11), ...201324041886
interleukin 22 inhibits intracellular growth of mycobacterium tuberculosis by enhancing calgranulin a expression.previously, we found that interleukin 22 (il-22) inhibits intracellular growth of mycobacterium tuberculosis in human monocyte-derived macrophages (mdms). in the current study, we determined the mechanisms underlying these effects. we found that w7, a phagolysosomal fusion inhibitor, abrogates il-22-dependent m. tuberculosis growth inhibition in mdms, suggesting that il-22 acts through enhanced phagolysosomal fusion. our microarray analysis indicated that recombinant il-22 (ril-22) enhances the ...201424041785
blood cells and interferon-gamma levels correlation in latent tuberculosis infection.the mycobacterium tuberculosis (m. tb) infection is largely spread in world's population. most infected individuals develop latent tuberculosis infection (ltbi). tuberculin skin test (tst) and interferon-gamma release assays (igras) are the available tests to detect the infection. it has been reported that some individuals take a longer period of time to develop the infection than others with the same exposure level. it is suggested that the innate immunity, in which neutrophils have an importan ...201324040564
fate of pup inside the mycobacterium proteasome studied by in-cell nmr.the mycobacterium tuberculosis proteasome is required for maximum virulence and to resist killing by the host immune system. the prokaryotic ubiquitin-like protein, pup-gge, targets proteins for proteasome-mediated degradation. we demonstrate that pup-ggq, a precursor of pup-gge, is not a substrate for proteasomal degradation. using stint-nmr, an in-cell nmr technique, we studied the interactions between pup-ggq, mycobacterial proteasomal atpase, mpa, and mtb proteasome core particle (cp) inside ...201324040288
analysis of host responses to mycobacterium tuberculosis antigens in a multi-site study of subjects with different tb and hiv infection states in sub-saharan africa.tuberculosis (tb) remains a global health threat with 9 million new cases and 1.4 million deaths per year. in order to develop a protective vaccine, we need to define the antigens expressed by mycobacterium tuberculosis (mtb), which are relevant to protective immunity in high-endemic areas.201324040170
ficolin-2 defends against virulent mycobacteria tuberculosis infection in vivo, and its insufficiency is associated with infection in humans.human ficolin-2 (ficolin-2/p35) is a lectin complement pathway activator that is present in normal human plasma and is associated with infectious diseases; however, little is known regarding the roles and mechanisms of ficolin-2 during mycobacterium tuberculosis (mtb) infection. here, we describe our novel findings that the ficolin-2 serum levels of 107 pulmonary tuberculosis (tb) patients were much lower compared with 107 healthy controls. in vitro analysis showed that ficolin-2 bound to the vi ...201324040095
why you should ask your patients about their fishing hobbies.patients who use immunosuppressive agents, in particular medication that blocks tumour necrosis factor-a, are at risk for mycobacterial infections. besides the typical mycobacterium tuberculosis infection, a lso a typical mycobacterial disease may occur. here we demonstrate two patients with such atypical mycobacterial infection due to swimming and fishing water contact. we propose that patients, before starting with immunosuppressive therapy, are counselled about risk factors for mycobacterial ...201324038562
free mycolic acid accumulation in the cell wall of the mce1 operon mutant strain of mycobacterium tuberculosis.the lipid-rich cell wall of mycobacterium tuberculosis, the agent of tuberculosis, serves as an effective barrier against many chemotherapeutic agents and toxic host cell effector molecules, and it may contribute to the mechanism of persistence. mycobacterium tuberculosis strains mutated in a 13-gene operon called mce1, which encodes a putative abc lipid transporter, induce aberrant granulomatous response in mouse lungs. because of the postulated role of the mce1 operon in lipid importation, we ...201324037657
the dpre1 enzyme, one of the most vulnerable targets of mycobacterium tuberculosis.the re-emergence of tuberculosis in recent years led the world health organization (who) to launch the stop tb strategy program. beside repurposing the existing drugs and exploring novel molecular combinations, an essential step to face the burden of tuberculosis will be to develop new drugs by identifying vulnerable bacterial targets. recent studies have focused on decaprenylphosphoryl-d-ribose oxidase (dpre1) of mycobacterium tuberculosis, an essential enzyme involved in cell wall metabolism, ...201324037308
characterisation of pks15/1 in clinical isolates of mycobacterium tuberculosis from mexico.tuberculosis (tb) is an infectocontagious respiratory disease caused by members of the mycobacterium tuberculosis complex. a 7 base pair (bp) deletion in the locus polyketide synthase (pks)15/1 is described as polymorphic among members of the m. tuberculosis complex, enabling the identification of euro-american, indo-oceanic and asian lineages. the aim of this study was to characterise this locus in tb isolates from mexico. one hundred twenty clinical isolates were recovered from the states of v ...201324037193
proteomic analysis of mycobacterium tuberculosis isolates resistant to kanamycin and amikacin.kanamycin (km) and amikacin (ak) are the key aminoglycoside drugs against tuberculosis (tb) and resistance to them severely affects the options for treatment. many explanations have been proposed for drug resistance to these drugs but still some mechanisms are unknown. proteins are the functional moiety of the cell and manifest in most of the biological processes; so, these are potential foci for the development of new therapeutics, diagnostics and vaccine. we examined the km and ak resistant is ...201324036035
autophagy regulates phagocytosis by modulating the expression of scavenger receptors.autophagy and phagocytosis are conserved cellular functions involved in innate immunity. however, the nature of their interactions remains unclear. we evaluated the role of autophagy in regulating phagocytosis in macrophages from myeloid-specific autophagy-related gene 7-deficient (atg7⁻/⁻) mice. atg7⁻/⁻ macrophages exhibited higher bacterial uptake when infected with mycobacterium tuberculosis (mtb) or with m. tuberculosis var. bovis bcg (bcg). in addition, bcg-infected atg7⁻/⁻ mice showed incr ...201324035364
trimethoprim/sulfamethoxazole susceptibility of mycobacterium tuberculosis. 201324035198
application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in tanzania.lack of rapid and reliable susceptibility testing for second-line drugs used in the treatment of multidrug-resistant tuberculosis (mdr-tb) may limit treatment success.201324034230
automated screening for tuberculosis by multiparametric analysis of data obtained during routine complete blood count.the main goal of this study was to develop a multiparametric cell population data (cpd) model that combines information from several morphologic parameters generated by dxh800, in addition to the traditional parameters regularly reported in the cbc-diff, and to test the performance of this model in screening the general population for primary tuberculosis (tb).201424034225
comparison of sensitivity of quantiferon-tb gold test and tuberculin skin test in active pulmonary tuberculosis.to compare the sensitivity of tuberculin skin test (tst) and quantiferon-tb gold test (qft-g) in active pulmonary tuberculosis.201324034187
tuberculous sacroiliitis in a renal transplant recipient: a case report.although mycobacterium tuberculosis (tb) is the predominant infectious disease after solid organ transplantation worldwide, extrapulmonary involvement in the sacroiliac (si) joint has never been reported in renal transplant patients. herein we have described a 59-year-old man who presented with left hip pain and fever at 1 year after renal transplantation. he had a positive patrick's test on the left hip, elevated serum c-reactive protein, and widening of left si joint on pelvic radiograph. alth ...201324034053
secretion of atypical protein substrates by the esat-6 secretion system of staphylococcus aureus.staphylococcus aureus encodes the specialized esat-6 secretion system (ess). esxa and esxb are secreted by the ess pathway, and share sequence features of esat-6 and cfp-10 of the type vii secretion system (t7ss) of mycobacterium tuberculosis. unlike esat-6 and cfp-10, esxa and esxb do not interact. instead, esxb associates with a novel substrate, esxd, and esxa dimerizes with itself or esxc (esac). unlike esxa and esxb, esxc and esxd do not share obvious sequence features of wxg100 proteins nor ...201324033479
v-type allosteric inhibition is described by a shift in the rate-determining step for α-isopropylmalate synthase from mycobacterium tuberculosis.the kinetic parameters affected by allosteric mechanisms contain collections of rate constants that vary based on differences in the relative rates of individual steps in the reaction. thus, it may not be useful to compare enzymes with similar allosteric mechanisms unless the point of regulation has been identified. rapid reaction kinetics and kinetic isotope effects provide a detailed description of v-type feedback allosteric inhibition in α-isopropylmalate synthase from mycobacterium tuberculo ...201324033269
reinterpreting the mechanism of inhibition of mycobacterium tuberculosis d-alanine:d-alanine ligase by d-cycloserine.d-cycloserine is a second-line drug approved for use in the treatment of patients infected with mycobacterium tuberculosis, the etiologic agent of tuberculosis. the unique mechanism of action of d-cycloserine, compared with those of other clinically employed antimycobacterial agents, represents an untapped and exploitable resource for future rational drug design programs. here, we show that d-cycloserine is a slow-onset inhibitor of mtddl and that this behavior is specific to the m. tuberculosis ...201324033232
a simple, rapid and economic method for detecting multidrug-resistant tuberculosis.to evaluate multiplex allele specific polymerase chain reaction as a rapid molecular tool for detecting multidrug-resistant tuberculosis.201324029439
rapid detection of drug resistance and mutational patterns of extensively drug-resistant strains by a novel genotype® mtbdrsl assay.the emergence of extensively drug-resistant tuberculosis (xdr-tb) is a major concern in the india. the burden of xdr-tb is increasing due to inadequate monitoring, lack of proper diagnosis, and treatment. the genotype ® mycobacterium tuberculosis drug resistance second line (mtbdrsl) assay is a novel line probe assay used for the rapid detection of mutational patterns conferring resistance to xdr-tb.201524029194
current status of multidrug resistant tuberculosis in a tertiary care hospital of east delhi.multidrug resistant tuberculosis (mdr-tb) is caused by infection due to mycobacterium tuberculosis which is resistant to both isoniazid (inh) and rifampicin (rif). it is caused by selection of resistant mutant strains due to inadequate treatment and poor compliance. mdr-tb is a major public health problem as the treatment is complicated, cure rates are well below those for drug susceptible tuberculosis and patient remains infectious for months despite receiving the best available therapy. the dr ...201524029192
multiple deletions in the polyketide synthase gene repertoire of mycobacterium tuberculosis reveal functional overlap of cell envelope lipids in host-pathogen interactions.several specific lipids of the cell envelope are implicated in the pathogenesis of m. tuberculosis (mtb), including phthiocerol dimycocerosates (dim) that have clearly been identified as virulence factors. others, such as trehalose-derived lipids, sulfolipids (sl), diacyltrehaloses (dat) and polyacyltrehaloses (pat), are believed to be essential for mtb virulence, but the details of their role remain unclear. we therefore investigated the respective contribution of dim, dat/pat and sl to tubercu ...201424028583
detection of rpob gene mutations using helicase-dependent amplification.for patients infected with tuberculosis, detection of rpob gene mutations is critical for diagnosing drug-resistant strains of the causative pathogen, mycobacterium tuberculosis (mtb). traditional approaches to drug resistance include culture, which is very slow. recently described real-time polymerase chain reaction approaches have addressed turnaround time but at relatively high cost. here, we describe a novel amplification method, termed blocked-primer helicase-dependent amplification, for am ...201324026688
publisher's expression of concern: geographical differences associated with snps in nine gene targets among resistant clinical isolates of mycobacterium tuberculosis.the american society for microbiology (asm) and the journal of clinical microbiology (jcm) are issuing this expression of concern to alert readers to questions about the ownership of the data in the following publication: m. hoshide, l. qian, c. rodrigues, r. warren, t. victor, h. b. evasco ii, t. tupasi, v. crudu, and j. t. douglas. geographic differences associated with snps in nine gene targets among resistant clinical isolates of mycobacterium tuberculosis. j. clin. microbiol. published ahea ...201324025906
mycobacterium tuberculosis detection in blood using multiplex nested polymerase chain reaction.polymerase chain reaction (pcr) offers great promise for the rapid, sensitive and specific diagnosis of tuberculosis (tb). however, blood tb pcr is still not standardised.201324025388
epidemiological evaluation of spatiotemporal and genotypic clustering of mycobacterium tuberculosis in ontario, canada.in canada, tuberculosis (tb) rates are at a historic low, with the remaining risk concentrated in a few vulnerable population subgroups.201324025385
dpre1, a new taxonomic marker in mycobacteria.among the species of the mycobacterium genus, more than 50 have been recognized as human pathogens. in spite of the different diseases caused by mycobacteria, the interspecies genetic similarity ranges from 94% to 100%, and for some species, this value is higher than in other bacteria. consequently, it is important to understand the relationships existing among mycobacterial species. in this context, the possibility to use mycobacterium tuberculosis dpre1 gene as new phylogenetic/taxonomic marke ...201324024613
no association of ifng+874t/a snp and nos2a-954g/c snp variants with nitric oxide radical serum levels or susceptibility to tuberculosis in a brazilian population subset.tuberculosis (tb) is one of the most common infectious diseases in the world. mycobacterium tuberculosis infection leads to pulmonary active disease in approximately 5-10% of exposed individuals. both bacteria- and host-related characteristics influence latent infection and disease. host genetic predisposition to develop tb may involve multiple genes and their polymorphisms. it was reported previously that interferon gamma (ifn-γ) and nitric oxide synthase 2 (nos2) are expressed on alveolar macr ...201324024215
directed evolution of mycobacterium tuberculosis β-lactamase reveals gatekeeper residue that regulates antibiotic resistance and catalytic efficiency.directed evolution can be a powerful tool for revealing the mutational pathways that lead to more resistant bacterial strains. in this study, we focused on the bacterium mycobacterium tuberculosis, which is resistant to members of the β-lactam class of antibiotics and thus continues to pose a major public health threat. resistance of this organism is the result of a chromosomally encoded, extended spectrum class a β-lactamase, blac, that is constitutively produced. here, combinatorial enzyme lib ...201324023821
unusual presentation of a culture-positive right atrial mass.we report a patient with a mass in the right atrium which led to pulmonary embolism. postoperatively the mass was identified as a tuberculoma and it was culture-positive for mycobacterium tuberculosis. patient responded to modified antitubercular treatment and discharged from hospital in satisfactory condition.201324023479
evaluation of the 2007 who guideline to diagnose smear negative tuberculosis in an urban hospital in ethiopia.the 2007 world health organization (who) guideline to diagnose smear-negative tuberculosis (tb) in hiv-prevalent settings was mainly based on expert advice and therefore requires evaluation in real life situations.201324020936
tmc207 becomes bedaquiline, a new anti-tb drug.tb still represents a serious public health problem. the latest reports estimate an incidence of 8.7 million cases in 2011 and 1.4 million deaths. drug resistance contributed an estimated 630,000 cases of multidrug-resistant tb, making control of the disease harder. recent reports show cases of tb that were almost resistant to all available antibiotics. therefore, there is an urgent need to develop new anti-tb drugs with the potential of reducing the current length of treatment. bedaquiline, for ...201324020736
tuberculous tenosynovitis and ulnar bursitis of the wrist.tuberculous infection of the hand is a rare form of extrapulmonary tuberculosis that, left untreated, can cause serious joint and tendon damage. we report the case of a 65-year-old male patient who presented with an insidious flexor weakness of the fifth finger but without any history of trauma. magnetic resonance imaging revealed a partial tear of the fifth finger flexor tendon with a fluid collection in the tendon sheath and in the flexor compartment along the ulnar side. under ultrasound guid ...201324020040
systematic analysis and prediction of pupylation sites in prokaryotic proteins.prokaryotic ubiquitin-like protein (pup) is the first identified prokaryotic protein that is functionally analogous to ubiquitin. recent studies have shed light on the pup activation and conjugation to target proteins to be a signal for the selective degradation proteins in mycobacterium tuberculosis (mtb). by covalently conjugating the pup, pupylation functions as a critical post-translational modification (ptm) conserved in actinomycetes. detecting pupylation sites is crucial and fundamental f ...201324019945
structural and biochemical analyses of mycobacterium tuberculosis n-acetylmuramyl-l-alanine amidase rv3717 point to a role in peptidoglycan fragment recycling.peptidoglycan hydrolases are key enzymes in bacterial cell wall homeostasis. understanding the substrate specificity and biochemical activity of peptidoglycan hydrolases in mycobacterium tuberculosis is of special interest as it can aid in the development of new cell wall targeting therapeutics. in this study, we report biochemical and structural characterization of the mycobacterial n-acetylmuramyl-l-alanine amidase, rv3717. the crystal structure of rv3717 in complex with a dipeptide product sh ...201324019530
nitrite impacts the survival of mycobacterium tuberculosis in response to isoniazid and hydrogen peroxide.when access to molecular oxygen is restricted, mycobacterium tuberculosis (mtb) can respire an alternative electron acceptor, nitrate. we found that mtb within infected primary human macrophages in vitro at physiologic tissue oxygen tensions respired nitrate, generating copious nitrite. a strain of mtb lacking a functioning nitrate reductase was more susceptible than wild-type mtb to treatment with isoniazid during infection of macrophages. likewise, nitrate reductase-deficient mtb was more susc ...201324019302
synthesis and evaluation of α-ketotriazoles and α,β-diketotriazoles as inhibitors of mycobacterium tuberculosis.two series of α-ketotriazole and α,β-diketotriazole derivatives were synthesized and evaluated for antitubercular and cytotoxic activities. among them, two α,β-diketotriazole compounds, 6b and 9b, exhibited good activities (minimum inhibitory concentration = 7.6 μm and 6.9 μm, respectively) on mycobacterium tuberculosis and multi-drug resistant m. tuberculosis strains and presented no cytotoxicity (ic₅₀ > 50 μm) on colorectal cancer hct116 and normal fibroblast gm637h cell lines. these two compo ...201324016834
mycobacterium tuberculosis dna gyrase atpase domain structures suggest a dissociative mechanism that explains how atp hydrolysis is coupled to domain motion.dna gyrase, a type ii topoisomerase, regulates dna topology by creating a double-stranded break in one dna duplex and transporting another dna duplex [t-dna (transported dna)] through this break. the atpase domains dimerize, in the presence of atp, to trap the t-dna segment. hydrolysis of only one of the two atps, and release of the resulting pi, is rate-limiting in dna strand passage. a long unresolved puzzle is how the non-hydrolysable atp analogue amp-pnp (adenosine 5'-[β,γ-imido]triphosphate ...201324015710
[the un-healing cause of its management after operation of thoracolumbar tuberculosis].to analyze the un-healing cause and management after operation of thoracolumbar tuberculosis.201324015663
host targeted activity of pyrazinamide in mycobacterium tuberculosis infection.pyrazinamide (pza) is one of the first line antibiotics used for the treatment of tuberculosis (tb). in the present study, we have used in vitro and in vivo systems to investigate whether pza, in addition to its known anti-mycobacterial properties, modulate the host immune response during mycobacterium tuberculosis (mtb) infection. in vitro we have examined the effect of pza on cytokine and chemokine release by mtb-infected or toll-like receptor (tlr) -stimulated primary human monocytes. in vivo ...201324015316
improved synthesis of capuramycin and its analogues.capuramycin and its congeners are considered to be important lead molecules for the development of a new drug for multidrug-resistant (mdr) mycobacterium tuberculosis infections. extensive structure-activity relationship studies of capuramycin to improve the efficacy have been limited because of difficulties in selectively chemically modifying the desired position(s) of the natural product with biologically interesting functional groups. we have developed efficient syntheses of capuramycin and i ...201324014478
syntheses and anti-tubercular activity of β-substituted and α,β-disubstituted peptidyl β-aminoboronates and boronic acids.tuberculosis is still affecting millions of people worldwide, and new resistant strains of mycobacterium tuberculosis are being found. it is therefore necessary to find new compounds for treatment. in this paper, we report the synthesis and in vitro testing of peptidyl β-aminoboronic acids and β-aminoboronates with anti-tubercular activity.201324014472
comparative genomics of the mycobacterium signaling architecture and implications for a novel live attenuated tuberculosis vaccine.tuberculosis (tb), caused by mycobacterium tuberculosis (m.tb), remains a major threat to global public health. a new tb vaccine affording superior immune protection to m. bovis bacillus calmette-guérin (bcg) is imperative. the advantage of a live attenuated vaccine is that it can mimic the bona fide pathogen, elicit immune responses similar to natural infection, and potentially provide more protection than other vaccines. bcg, the only vaccine and a live attenuated vaccine that is the result of ...201424013364
evolution and role of corded cell aggregation in mycobacterium tuberculosis cultures.the aim of this study was to evaluate the evolution and role of corded cell aggregation in mycobacterium tuberculosis cultures according to growth time and conditions. thus, in standard culture using aerated 7h9 middlebrook broth supplemented with 0.05% tween 80, a dramatic cfu decrease was observed at the end of the exponential phase. this phase was followed by a stable stationary phase that led to dissociation between the optical density (o.d.) and cfu values, together with the formation of op ...201324011631
ethnicity-tailored novel set of esat-6 peptides for differentiating active and latent tuberculosis.differentiation between active and latent tb is a diagnostic challenge in tb-endemic regions. the commercially available ifn-γ-release assays are unsuitable for achieving this discrimination. we, therefore, screened esat-6 and cfp-10 proteins through population coverage analysis to identify minimal sets of peptides that can discriminate between these two forms of tb in a north indian population. comparing the diagnostic performance of a set of 2 esat-6 peptides (positions: 16-36; 59-79) to that ...201324011630
aminopeptidase n facilitates entry and intracellular survival of mycobacterium tuberculosis in monocytes.aminopeptidase n (cd13) is an ectoenzyme located in the outer membrane of a variety of cells. proteomic profiling indicates an increased expression of cd13 in phagocytes during mycobacterium tuberculosis infection. the purpose of this study was to investigate the role of cd13 on the internalization and intracellular survival of m. tuberculosis in monocytes.201424011358
molecular characterization of t cell receptor beta variable in the peripheral blood t cell repertoire in subjects with active tuberculosis or latent tuberculosis infection.t cells are closely linked to the clinical manifestations of subjects with mycobacterium tuberculosis (mtb) infection. t cell receptor beta variable (tcrbv) is a signal and indicative molecule on the membrane of t lymphocytes, reflecting the composition and specificity of t cells. the molecular profiles of tcrbv in peripheral blood mononuclear cells (pbmcs) and their subpopulations (cd4+ and cd8+ t cells) from subjects with active tuberculosis (tb) or latent tb infection (ltbi) have not been wel ...201324010943
prospective multicentre evaluation of the direct nitrate reductase assay for the rapid detection of extensively drug-resistant tuberculosis.to perform a multicentre study evaluating the performance of the direct nitrate reductase assay (nra) for the detection of multidrug-resistant (mdr) and extensively drug-resistant (xdr) tuberculosis in sputum samples.201424008825
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