| characterization of pyrazinamide resistance in consecutive multidrug-resistant mycobacterium tuberculosis isolates in sweden between 2003 and 2015. | the first line anti-tuberculosis drug pyrazinamide (pza) is important when treating pza susceptible multidrug-resistant tuberculosis (mdr-tb). several drug resistance surveys have however reported pza resistance among a significant proportion of multidrug-resistant (mdr) cases and this undoubtedly highlights the need for accurate and reliable detection of pza resistance. unfortunately, the testing of pza susceptibility is associated with technical difficulties and even though the introduction of ... | 2017 | 28559517 |
| in silico structure-based drug screening of novel antimycobacterial pharmacophores by dock-gold tandem screening. | enzymes responsible for cell wall development in mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (tb) agents. mycobacterial cyclopropane mycolic acid synthase 1 (cmaa1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. | 2017 | 28559515 |
| diagnostic performance of genotype(®) mtbdrplus line probe assay in bronchoalveolar lavage for pulmonary tuberculosis diagnosis in sputum scarce and smear-negative patients. | mtbdrplus line probe assay (lipa) has been endorsed by the world health organization for pulmonary tuberculosis (tb) diagnosis. however, its value for mycobacterium tuberculosis (mtb) detection in bronchoalveolar lavage (bal) needs exploration. this study determined the diagnostic performance of mtbdrplus in bal for mtb complex detection and isoniazid/rifampicin resistance in smear-negative and sputum scarce patients. | 2017 | 28559511 |
| rapid detection of in vitro antituberculous drug resistance among smear-positive respiratory samples using microcolony detection-based direct drug susceptibility testing method. | with the rise in multidrug-resistant tuberculosis, there is a search for newer techniques that will rapidly detect drug-resistant mycobacterium tuberculosis. although molecular techniques can detect resistance, culture is still considered gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. the aim of the study was to evaluate microcolony method thin layer agar (tla) for quick detection of resistance against the first- and second-line antitub ... | 2017 | 28559510 |
| rifamycin action on rna polymerase in antibiotic-tolerant mycobacterium tuberculosis results in differentially detectable populations. | mycobacterium tuberculosis (mtb) encounters stresses during the pathogenesis and treatment of tuberculosis (tb) that can suppress replication of the bacteria and render them phenotypically tolerant to most available drugs. where studied, the majority of mtb in the sputum of most untreated subjects with active tb have been found to be nonreplicating by the criterion that they do not grow as colony-forming units (cfus) when plated on agar. however, these cells are viable because they grow when dil ... | 2017 | 28559332 |
| pharmacokinetic evidence from the hirif trial to support increased doses of rifampin for tuberculosis. | rifamycins exhibit concentration-dependent killing of mycobacterium tuberculosis; higher exposures potentially induce better outcomes. we randomized 180 tuberculosis patients in peru to receive rifampin at 10, 15, or 20 mg/kg/day. a total of 168 had noncompartmental pharmacokinetic analyses; 67% were sampled twice, and 33% were sampled six times. the doses administered were well tolerated. the median area under the concentration-time curve from 0 to 6 h (interquartile range) was 24.9 (17.6 to 32 ... | 2017 | 28559269 |
| metformin adjunctive therapy does not improve the sterilizing activity of the first-line antitubercular regimen in mice. | preliminary preclinical and observational studies suggest the potential utility of metformin as an adjunctive, host-directed agent for treatment of tuberculosis (tb). in this study, we sought to investigate the bactericidal and sterilizing activities of human-like exposures of metformin when given in combination with the first-line regimen against chronic tuberculosis in balb/c mice. mice receiving metformin adjunctive therapy had similar lung bacillary burdens with control mice during treatment ... | 2017 | 28559262 |
| evaluation of gene xpert for routine diagnosis of hiv-associated tuberculosis in nigeria: a prospective cohort study. | xpert mtb/rif (xpert) is described as a game changer in tuberculosis (tb) control. we evaluated the impact of xpert on diagnosis, time to treatment, and treatment outcome among patients with hiv associated tb in nigeria. | 2017 | 28558662 |
| prediabetes is associated with the modulation of antigen-specific th1/tc1 and th17/tc17 responses in latent mycobacterium tuberculosis infection. | type 2 diabetes mellitus (dm) is associated with the down modulation of th1, th2 and th17 responses in latent mycobacterium tuberculosis infection but the role of prediabetes (pdm) in this setting is not well understood. to examine the role of cd4+ and cd8+ t cell cytokines in latent tuberculosis (ltb) with coincident pdm, we studied the baseline, mycobacterial, control antigen and mitogen-stimulated t cell cytokine responses in ltb individuals with (ltb-pdm; n = 20) or without (ltb-ndm; n = 20) ... | 2017 | 28558065 |
| microrna 26a (mir-26a)/klf4 and creb-c/ebpβ regulate innate immune signaling, the polarization of macrophages and the trafficking of mycobacterium tuberculosis to lysosomes during infection. | for efficient clearance of mycobacterium tuberculosis (mtb), macrophages tilt towards m1 polarization leading to the activation of transcription factors associated with the production of antibacterial effector molecules such as nitric oxide (no) and proinflammatory cytokines such as interleukin 1 β (il-1β) and tumor necrosis factor α (tnf-α). at the same time, resolution of inflammation is associated with m2 polarization with increased production of arginase and cytokines such as il-10. the tran ... | 2017 | 28558034 |
| distance learning course for healthcare professionals: continuing education in tuberculosis. | continuing education of healthcare workers (hcws) is an essential strategy for the control of tuberculosis (tb) transmission, enabling hcws in early detection and appropriate treatment of tb cases. | 2017 | 28557658 |
| what we have learned and what we have missed in tuberculosis pathophysiology for a new vaccine design: searching for the "pink swan". | this is a call to encourage the search for a new vaccine to stop the progression of mycobacterium tuberculosis infection to tuberculosis (tb) disease. tb is a highly discreet and stigmatized disease, with a massive impact on human health. it has killed 1.2 billion people in the last 200 years and still kills 1.5 million people per year. over the last 20 years, the tb vaccine field has experienced spectacular developments, and we have learned about (1) the importance of the th1 response in contro ... | 2017 | 28555137 |
| strategic incorporation of fluorine in the drug discovery of new-generation antitubercular agents targeting bacterial cell division protein ftsz. | this article presents an account of our research on the discovery and development of new-generation fluorine-containing antibacterial agents against drug-resistant tuberculosis, targeting ftsz. ftsz is an essential protein for bacterial cell division and a highly promising therapeutic target for antibacterial drug discovery. through design, synthesis and semi-htp screening of libraries of novel benzimidazoles, followed by sar studies, we identified highly potent lead compounds. however, these le ... | 2017 | 28555087 |
| multiplex pcr assay for genotyping of mycobacterium tuberculosis in lima, peru. | | 2017 | 28554706 |
| electrochemical determination of m. tuberculosis antigen based on poly(3,4-ethylenedioxythiophene) and functionalized carbon nanotubes hybrid platform. | an electrochemical dna aptasensor for the detection of mycobacterium tuberculosis (m. tb) antigen mpt64, was developed using poly(3,4-ethylenedioxythiophene) (pedot) doped with carbon nanotubes (cnts). the biotinylated aptamer was immobilized onto streptavidin attached to -cooh functionalized cnts via streptavidin-biotin interaction. various characterization studies as ft-ir, fe-sem, eis and dpv were done to validate each fabrication step of the aptasensor. optimization studies related to aptame ... | 2017 | 28551117 |
| [multidrug-resistant tuberculosis by strains of beijing family, in patients from lisbon, portugal: preliminary report]. | beijing family strains of mycobacterium tuberculosis are associated with multidrug-resistance. although strains of the lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the beijing family. however, the features of patients from whom they were isolated, are not yet known. | 2017 | 28550826 |
| the role of molecular techniques for the detection of mycobacterium tuberculosis complex in paraffin-embedded biopsies. | extrapulmonary tuberculosis (eptb) is increasingly frequent in developed countries. when it is not clinically suspected, samples are not collected for culture and the only material available is a tissue paraffin block. | 2017 | 28549036 |
| efficacy of β-lactam/β-lactamase inhibitor combination is linked to whib4-mediated changes in redox physiology of mycobacterium tuberculosis. | mycobacterium tuberculosis (mtb) expresses a broad-spectrum β-lactamase (blac) that mediates resistance to one of the highly effective antibacterials, β-lactams. nonetheless, β-lactams showed mycobactericidal activity in combination with β-lactamase inhibitor, clavulanate (clav). however, the mechanistic aspects of how mtb responds to β-lactams such as amoxicillin in combination with clav (referred as augmentin [ag]) are not clear. here, we identified cytoplasmic redox potential and intracellula ... | 2017 | 28548640 |
| restimulation-induced t-cell death through ntb-a/sap signaling pathway is impaired in tuberculosis patients with depressed immune responses. | production of ifn-γ contributes to host defense against mycobacterium tuberculosis (mtb) infection. we previously demonstrated that signaling lymphocytic activation molecule-associated protein (sap) expression on cells from tuberculosis (tb) patients was inversely correlated with ifn-γ production. here we first investigated the role of nk, t- and b-cell antigen (ntb-a)/sap pathway in the regulation of th1 response against mtb. upon antigen stimulation, ntb-a phosphorylation rapidly increases and ... | 2017 | 28546549 |
| genetic diversity of mycobacterium tuberculosis isolates from tochigi prefecture, a local region of japan. | foreign-born patients with tuberculosis (tb) may introduce globally disseminated isolates of mycobacterium tuberculosis into large cities in japan. the risk of dissemination of these isolates into local regions, however, has not been determined. this study analyzed the molecular epidemiology of m. tuberculosis isolates obtained from tb patients living in a local region of japan. | 2017 | 28545488 |
| thymoquinone (tq) inhibits the replication of intracellular mycobacterium tuberculosis in macrophages and modulates nitric oxide production. | human tuberculosis, which is caused by the pathogen mycobacterium tuberculosis, remains a major public health concern. increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. thymoquinone (tq), an essential compound of nigella sativa, was previously reported as an active anti-tuberculosis agent. | 2017 | 28545436 |
| structural insight into the inactivation of mycobacterium tuberculosis non-classical transpeptidase ldtmt2 by biapenem and tebipenem. | the carbapenem subclass of β-lactams is among the most potent antibiotics available today. emerging evidence shows that, unlike other subclasses of β-lactams, carbapenems bind to and inhibit non-classical transpeptidases (l,d-transpeptidases) that generate 3 → 3 linkages in bacterial peptidoglycan. the carbapenems biapenem and tebipenem exhibit therapeutically valuable potencies against mycobacterium tuberculosis (mtb). | 2017 | 28545389 |
| assessment of the quantiferon-tb gold in-tube test for the detection of mycobacterium tuberculosis infection in united states navy recruits. | immunologic tests such as the tuberculin skin test (tst) and quantiferon®-tb gold in-tube test (qft-git) are designed to detect mycobacterium tuberculosis infection, both latent m. tuberculosis infection (ltbi) and infection manifesting as active tuberculosis disease (tb). these tests need high specificity to minimize unnecessary treatment and high sensitivity to allow maximum detection and prevention of tb. | 2017 | 28545136 |
| pkng senses amino acid availability to control metabolism and virulence of mycobacterium tuberculosis. | sensing and response to changes in nutrient availability are essential for the lifestyle of environmental and pathogenic bacteria. serine/threonine protein kinase g (pkng) is required for virulence of the human pathogen mycobacterium tuberculosis, and its putative substrate gara regulates the tricarboxylic acid cycle in m. tuberculosis and other actinobacteria by protein-protein binding. we sought to understand the stimuli that lead to phosphorylation of gara, and the roles of this regulatory sy ... | 2017 | 28545104 |
| prevalence and extent of heteroresistance by next generation sequencing of multidrug-resistant tuberculosis. | amplicon-based next generation sequencing (ngs) is an emerging method for mycobacterium tuberculosis drug susceptibility testing (dst) but has not been well described. we examined 158 clinical multidrug-resistant m. tuberculosis isolates via ngs of 11 resistance-associated gene regions covering 3519 nucleotides. across these gene regions, complete resistance or heteroresistance (defined as 1%-99% mutation) was present in at least one isolate in 6.3% of loci. the number of isolates with heterores ... | 2017 | 28545050 |
| phenotypic assays for mycobacterium tuberculosis infection. | tuberculosis (tb) is still a major global threat, killing more than one million persons each year. with the constant increase of mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of tb. although screenings of small molecules on axenic m. tuberculosis cultures were successful for the identification of novel putative anti-tb drugs, new drugs in the development pipeline remains scarce. ho ... | 2017 | 28544095 |
| application of molecular, microbiological, and immunological tests for the diagnosis of bone and joint tuberculosis. | to evaluate the application of interferon gamma release assay (igra), rifampicin resistant real-time fluorescence quantitative pcr technique xpert mycobacterium tuberculosis/rifampicin (xpert mtb/rif), and the levels of tnf-α and tgf-β in the diagnosis of bone and joint tuberculosis. | 2017 | 28543876 |
| influence of diabetes mellitus on immunity to human tuberculosis. | type 2 diabetes mellitus(dm) is a major risk factor for the development of active pulmonary tuberculosis (tb), with development of dm pandemic in countries where tb is also endemic. understanding the impact of dm on tb and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. despite the clinical and public health significance posed by the dual burden of tb and dm, little is known about the immunological and bioche ... | 2017 | 28543817 |
| activation of mmps in macrophages by mycobacterium tuberculosis via the mir-223-bmal1 signaling pathway. | an interaction between mycobacterium tuberculosis and macrophages constitutes an essential step in tuberculosis development, as macrophages exert both positive and negative effects on m. tuberculosis-triggered organ lesions. in this study, we focused on the regulation of the expression of matrix metalloproteinases (mmps), which is responsible for lung matrix degradation and bacteria dissection, in macrophages following m. tuberculosis infection. female balb/c mice were intravenously injected wit ... | 2017 | 28543681 |
| gallium nanoparticles facilitate phagosome maturation and inhibit growth of virulent mycobacterium tuberculosis in macrophages. | new treatments and novel drugs are required to counter the growing problem of drug-resistant strains of mycobacterium tuberculosis (m.tb). our approach against drug resistant m.tb, as well as other intracellular pathogens, is by targeted drug delivery using nanoformulations of drugs already in use, as well as drugs in development. among the latter are gallium (iii) (ga)-based compounds. in the current work, six different types of ga and rifampin nanoparticles were prepared in such a way as to en ... | 2017 | 28542623 |
| mycobacterium tuberculosis arrests host cycle at the g1/s transition to establish long term infection. | signals modulating the production of mycobacterium tuberculosis (mtb) virulence factors essential for establishing long-term persistent infection are unknown. the whib3 redox regulator is known to regulate the production of mtb virulence factors, however the mechanisms of this modulation are unknown. to advance our understanding of the mechanisms involved in whib3 regulation, we performed mtb in vitro, intraphagosomal and infected host expression analyses. our mtb expression analyses in conjunct ... | 2017 | 28542477 |
| detection of mycobacterium tuberculosis from the stool of hiv sero-positive individuals suspected of pulmonary tuberculosis. | the impact of tuberculosis (tb) is exacerbated in africa because of the human immunodeficiency virus (hiv) pandemic. pulmonary tuberculosis (ptb) diagnosis is difficult in hiv-infected patients and negative sputum results are more common which leads to diagnostic delay and increases morbidity and mortality. extra-pulmonary samples such as stool may be easier to obtain and our approach may therefore significantly improve ptb detection in people living with hiv. | 2017 | 28542255 |
| genital tuberculosis: current status of diagnosis and management. | genitourinary tuberculosis (gutb) is the second most common extra-pulmonary manifestation of tuberculosis (tb) and an isolated involvement of genital organs is reported in 5-30% of the cases. genital involvement results from primary reactivation of latent bacilli either in the epididymis or the prostate or by secondary spread from the already infected urinary organs. the epididymis are the commonest involved organs affected primarily by a hematogenous mode of spread. tb is characterized by exten ... | 2017 | 28540230 |
| mannose-binding lectin (mbl) gene polymorphisms in susceptibility to pulmonary tuberculosis among the lur population of lorestan province of iran. | tuberculosis (tb) is caused by infection of mycobacterium tuberculosis. host genetic variability is an important determinant of the risk of developing tb in humans. although the association between mbl polymorphisms and tb has been studied in various populations, the results are controversial. the aim of this study was to investigate mannose-binding lectin (mbl) gene polymorphisms with susceptibility to pulmonary tuberculosis (ptb) in a lur population of iran. | 2017 | 28540182 |
| low levels of extensively drug-resistant tuberculosis among multidrug resistant tuberculosis isolates and their relationship to risk factors: surveillance in tehran, iran; 2006 to 2014. | extensively drug-resistant tuberculosis (xdr-tb) is more expensive and difficult to treat than multidrug-resistant tuberculosis (mdr-tb), and outcomes for patients are much worse; therefore, it is important that clinicians understand the magnitude and distribution of xdr-tb. we conducted a retrospective study to compare the estimated incidence of and risk factors for m/xdr-tb with those of susceptible tb controls. | 2017 | 28540155 |
| protecting pyrazinamide, a priority for improving outcomes in multidrug-resistant tuberculosis treatment. | | 2017 | 28539498 |
| the tyrosine kinase inhibitor gefitinib restricts mycobacterium tuberculosis growth through increased lysosomal biogenesis and modulation of cytokine signaling. | host-directed therapeutics have the potential to combat the global tuberculosis pandemic. we previously identified gefitinib, an inhibitor of egfr, as a potential host-targeted therapeutic effective against mycobacterium tuberculosis infection of macrophages and mice. here we examine the functional consequences of gefitinib treatment on m. tuberculosis infected macrophages. using phosphoproteomic and transcriptional profiling, we identify two mechanisms by which gefitinib influences macrophage r ... | 2017 | 28537707 |
| expansion of cd25-negative forkhead box p3-positive t cells during hiv and mycobacterium tuberculosis infection. | tuberculosis (tb) and hiv alter the immune system, and coinfected (hiv-tb) individuals usually present deregulations of t-lymphocytic immune response. we previously observed an increased frequency of "unconventional" cd4(+)cd25(-)foxp3(+) treg (utreg) population during hiv-tb disease. therefore, we aimed to explore the phenotype and function of utreg and conventional cd4(+)cd25(+)foxp3(+) treg subsets (ctreg) in this context. we evaluated the expression of cd39, programmed cell death protein 1 ( ... | 2017 | 28536578 |
| comparative proteomic analysis of mycobacterium tuberculosis lineage 7 and lineage 4 strains reveals differentially abundant proteins linked to slow growth and virulence. | in order to decipher the nature of the slowly growing mycobacterium tuberculosis (m.tuberculosis) lineage 7, the differentially abundant proteins in strains of m. tuberculosis lineage 7 and lineage 4 were defined. comparative proteomic analysis by mass spectrometry was employed to identify, quantitate and compare the protein profiles of strains from the two m. tuberculosis lineages. label-free peptide quantification of whole cells from m. tuberculosis lineage 7 and 4 yielded the identification o ... | 2017 | 28536560 |
| effects of hmasp-2 on the formation of bcg infection-induced granuloma in the lungs of balb/c mice. | tuberculosis, caused by mycobacterium tuberculosis, affects the functions of the lung and causes high morbidity and mortality rates worldwide. masp-2 is an executioner enzyme, which plays an essential role in the activation of lectin pathway. in our previous studies, the masp-2 played a dual role in promoting the progress of lesions in bcg-infected rabbit skin models. however, the really effects of masp-2 on tuberculosis are unknown. the aim of this study was to investigate the effects of masp-2 ... | 2017 | 28536447 |
| treatment of latent tuberculosis in patients with juvenile rheumatic diseases: a systematic review. | children and adolescents with rheumatic diseases receiving tnf blockers are at risk for the activation of latent mycobacterium tuberculosis infection (ltbi). although ltbi treatment is indicated in this group, there are different therapeutic regimens in the literature, without a definite consensus. | 2017 | 28535897 |
| differential carriage of virulence-associated loci in the new zealand rangipo outbreak strain of mycobacterium tuberculosis. | the rangipo strain of mycobacterium tuberculosis achieved notoriety in new zealand due to its role in several tuberculosis (tb) outbreaks. why this strain should be the source of relatively large clusters of the disease is unknown. in this work, we performed an in-depth analysis of the genome of the rangipo strain to determine whether it offers clues to understanding its prevalence. | 2017 | 28535727 |
| are moxifloxacin and levofloxacin equally effective to treat xdr tuberculosis? | moxifloxacin retains partial activity against some fluoroquinolone-resistant mutants of mycobacterium tuberculosis . levofloxacin is presumed to be as active as moxifloxacin against drug-susceptible tuberculosis and to have a better safety profile. | 2017 | 28535203 |
| genomic insight into mechanisms of reversion of antibiotic resistance in multidrug resistant mycobacterium tuberculosis induced by a nanomolecular iodine-containing complex fs-1. | drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. however, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. induction of antibiotic resistance reversion by a new anti-tuberculosis drug fs-1 has been reported. fs-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug r ... | 2017 | 28534009 |
| ifn-γ and il-2 responses to recombinant aladh against esat-6/cfp-10 fusion antigens in the diagnosis of latent versus active tuberculosis infection. | discriminating latent tuberculosis infection (ltbi) from active tbi may be challenging. the objective of this study was to produce the recombinant l-alanine dehydrogenase (aladh) antigen and evaluate individuals with ltbi, those with active tbi, and uninfected individuals by enzyme-linked immunospot assay (elispot) in order to distinguish ltbi from active tbi. | 2017 | 28533576 |
| host-directed therapies offer novel opportunities for the fight against tuberculosis. | tuberculosis (tb) remains a leading global health problem that is exacerbated by the emergence of multidrug and extensively drug-resistant mycobacterium tuberculosis strains. control of the disease requires novel therapeutic strategies. modulating host homeostasis appears to be a promising approach, and recent studies have identified novel potential host targets and compounds that could be investigated for host-directed therapies (hdts). moreover, the recent development of intracellular high-thr ... | 2017 | 28533187 |
| the novel gene mtb192 is a candidate marker for the detection of multidrug-resistant mycobacterium tuberculosis strains. | multi-drug resistant tuberculosis (tb) is one of the most main threats to the global tb control work at present. and it's very difficult to detect. from a screen of differentially expressed genes in multidrug-resistant tuberculosis (mdr-tb) strains, we identified a new gene, mtb192. in the present study, we verified the association of mtb192 with tb drug resistance by detecting its expression in clinical isolates from paediatric tb patients. | 2017 | 28533124 |
| utility of th1-cell immune responses for distinguishing active tuberculosis from non-active tuberculosis: a case-control study. | currently available interferon-γ release assay (igra) cannot reliably differentiate active tb (atb) from non-active tb (non-atb). a study was performed to evaluate the value of mycobacterium tuberculosis (mtb) specific th1 cell immune responses which test ifn-γ and il-2 simultaneous for differentiating atb from non-atb. forty-nine newly diagnosed inpatients with atb (26 pulmonary tb and 23 extrapulmonary tb) were enrolled as the atb group. forty-five volunteers with latent tuberculosis infection ... | 2017 | 28531231 |
| metabolic anticipation in mycobacterium tuberculosis. | humans serve as both host and reservoir for mycobacterium tuberculosis, making tuberculosis a theoretically eradicable disease. how m. tuberculosis alternates between host-imposed quiescence and sporadic bouts of replication to complete its life cycle, however, remains unknown. here, we identify a metabolic adaptation that is triggered upon entry into hypoxia-induced quiescence but facilitates subsequent cell cycle re-entry. catabolic remodelling of the cell surface trehalose mycolates of m. tub ... | 2017 | 28530656 |
| association of single-nucleotide polymorphism in the hepcidin promoter gene with susceptibility to extrapulmonary tuberculosis. | hepcidin is a 25-amino acid peptide produced by the liver in response to inflammation and iron overload. it is encoded by the hepcidin antimicrobial peptide (hamp) gene and plays a key role in innate immunity. previous studies have reported that a -582 a>g polymorphism in the hamp promoter (hamp-p) affects hepcidin expression, causing susceptibility to various bacterial and viral pathogens. however, it is not known whether the hamp-p -582 a>g polymorphism is associated with tuberculosis (tb) sus ... | 2017 | 28530443 |
| tuberculous spondylitis of the craniovertebral junction. | craniovertebral junction tuberculosis is rare, accounting for 0.3 to 1% of all tuberculous spondylitis cases. mr imaging is the modality of choice to detect bone involvement, abscess formation and subligamentous spreading of the pus, to differentiate from other lesions affecting the craniovertebral junction, and to determine the efficacy of treatment. given the fact that surgical treatment of patients with craniovertebral junction tuberculosis has been associated with a high mortality rate rangi ... | 2016 | 28529850 |
| copper and antibiotics: discovery, modes of action, and opportunities for medicinal applications. | copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. however, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including dna, lipids, and proteins. to restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copp ... | 2017 | 28528648 |
| molecular diagnosis of tubercular lymphadenopathy from fine-needle aspirates in pediatric patients. | the diagnosis of peripheral tubercular lymphadenopathy (tbln) in pediatric patients is often a challenge because features evident on fine-needle aspiration cytology (fnac) or tissue biopsy can be deceptive for the reason that they result from an immunological response. this study aimed to evaluate polymerase chain reaction (pcr) for mycobacterium tuberculosis complex (mtbc) in pediatric patients under clinical suspicion for tbln and to assess its role in the evaluation of cases cytodiagnosed as ... | 2017 | 28528339 |
| immuno-pcr, a new technique for the serodiagnosis of tuberculosis. | rapid and accurate diagnosis of tuberculosis (tb) is essential to control the disease. the conventional microbiological tests have limitations and there is an urgent need to devise a simple, rapid and reliable point-of-care (poc) test. the failure of tb diagnostic tests based on antibody detection due to inconsistent and imprecise results has stimulated renewed interest in the development of rapid antigen detection methods. however, the world health organization (who) has emphasized to continue ... | 2017 | 28527886 |
| new 1-hydroxy-2-thiopyridine derivatives active against both replicating and dormant mycobacterium tuberculosis. | tuberculosis (tb) treatment is confounded by the range of metabolic states displayed by mycobacterium tuberculosis, by the long duration required and by the increasing prevalence of drug-resistant strains. latent tb infection is especially difficult to treat due to the phenotypic antibiotic resistance of non-replicating m. tuberculosis. therefore, the development of new drugs effective against both active and latent tb infection is needed. new 1-hydroxy-2-thiopyridine derivatives were synthesize ... | 2017 | 28527650 |
| [identification of the mycobacterium tuberculosis beijing lineage in ecuador]. | mycobacterium tuberculosis beijing lineage isolates are considered to be especially virulent, transmissible and prone to acquire resistances. beijing strains have been reported worldwide, but studies in latin america are still scarce. the only multinational study performed in the region indicated a heterogeneous distribution for this lineage, which was absent in chile, colombia and ecuador, although further studies found the lineage in chile and colombia. | 2017 | 28527287 |
| [performance of led fluorescence microscopy for the detection of acid-fast bacilli from respiratory samples in peripheral laboratories in argentina]. | light-emitting diode fluorescence microscopy (led-fm) has been endorsed by the world health organization (who) for tuberculosis diagnosis, but its accuracy in hiv-infected patients remains controversial, and only some few studies have explored procedural factors that may affect its performance. | 2017 | 28527280 |
| [prevalence of mycobacterium tuberculosis resistance to quinolones and injectables in colombia, 2012-2013]. | tuberculosis is a health problem worldwide. the world health organization estimated 9.6 million new cases and 480,000 multirresistant cases for 2014. the assessment of resistance to quinolones and injectables was implemented only a few years ago, so its prevalence is not known. | 2017 | 28527253 |
| [characterization of clinical isolates of mycobacterium tuberculosis from hiv positive individuals in colombia, 2012]. | one third of the increase in tuberculosis cases is attributed to the spread of hiv. in 2012, 1,397 hiv-associated tuberculosis cases were reported in colombia, i.e., 11.8% of the total cases. molecular epidemiology tools help to understand the transmission of tuberculosis. | 2017 | 28527252 |
| [description of mycobacterium tuberculosis mutations conferring resistance to rifampicin and isoniazid detected by genotype® mtbdrplus v.2 in colombia]. | the genotype®mtbdrplusv.2 assay is a molecular technique endorsed by the world health organization and the pan american health organization that allows for the identification of the mycobacterium tuberculosis complex and the detection of mutations in the rpoβ gene for rifampicin resistance, and katg and inha genes for isoniazid resistance. due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these ... | 2017 | 28527245 |
| adoptive transfer of phosphoantigen-specific γδ t cell subset attenuates mycobacterium tuberculosis infection in nonhuman primates. | the dominant vγ2vδ2 t cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. despite the discovery of γδ t cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the vγ2vδ2 t cell subset is protective against mycobacterium tuberculosis and other infections. in this study, we used an adoptive cell-transfer strategy to define the protective role of vγ2vδ2 t cells in a primate tuberculosis (tb) model. vγ2vδ2 t cells for adoptive trans ... | 2017 | 28526681 |
| challenges in the estimation of the annual risk of mycobacterium tuberculosis infection in children aged under 5 years. | accurate estimates of mycobacterium tuberculosis (m.tb) infection in young children provide a critical indicator of on-going community m.tb transmission. cross reactions due to infection with environmental mycobacteria and/or bacille calmette-guérin (bcg) vaccination compromise the estimates derived from population-level tuberculin skin test surveys using traditional cut-off methods. newer statistical approaches are prone to failure of model convergence, especially in settings where the prevalen ... | 2017 | 28525582 |
| unaffected reaction level in tuberculin skin test by long-term therapy with tumor necrosis factor inhibitors for rheumatoid arthritis. | the tuberculin skin test (tst) is used to diagnose tuberculosis; however, the influence of tumor necrosis factor (tnf) inhibitors on the test is unclear. this study investigated whether therapy with tnf inhibitors suppresses the tst reaction due to immunosuppression or whether the tst reaction increases due to reactivation of latent mycobacterium tuberculosis infection. | 2017 | 28524434 |
| discovery of fluorine-containing benzoxazinyl-oxazolidinones for the treatment of multidrug resistant tuberculosis. | a novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. compound 21 exhibited not only outstanding in vitro activity with a mic value of 0.25-0.50 μg/ml against drug-susceptible h37rv strain and two clinically isolated drug-resistant mycobacterium tuberculosis strains, but also acceptable in vitro adme/t properties. moreover, this compound displayed ex ... | 2017 | 28523106 |
| evaluation of xpert mtb/rif assay performance in the diagnosis of abdominal tuberculosis. | the use of genetic probes for the diagnosis of pulmonary tuberculosis (tb) has been well described. however, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. we therefore assessed the diagnostic utility of the xpert mycobacterium tuberculosis/rifampicin (mtb/rif) assay, and estimated the prevalence of multidrug-resistant (mdr) tb in the indian population. | 2017 | 28522948 |
| knowns and unknowns of membrane lipid synthesis in streptomycetes. | bacteria belonging to the genus streptomyces are among the most prolific producers of antibiotics. research on cellular membrane biosynthesis and turnover is lagging behind in streptomyces compared to related organisms like mycobacterium tuberculosis. while natural products discovery in streptomyces is evidently a priority in order to discover new antibiotics to combat the increase in antibiotic resistant pathogens, a better understanding of this cellular compartment should provide insights into ... | 2017 | 28522365 |
| potential of multi-component antigens for tuberculosis diagnosis. | tuberculosis is one of the top ten causes of deaths worldwide. the cause of tuberculosis is a bacterium, mycobacterium tuberculosis, which has been surviving for centuries. immunological tests based on detecting the presence of antibodies in the sera of active tb patients against various antigens of m. tuberculosis are useful for diagnosis of tb and offer simple, rapid and cost effective methods most suitable for poor and developing countries. several recombinant antigens have been reported so f ... | 2017 | 28522247 |
| disseminated bacillus calmette-guérin osteomyelitis in twin sisters related to stat1 gene deficiency. | mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as bacillus calmette-guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. since 1996, 9 genes including 7 autosomal ( stat1, ifngr1, ifngr2, il12b, il12rb1, isg15, and irf8) and 2 x-linked genes ( nemo and cybb) have been identified. allelic heterogeneity ... | 2017 | 28521627 |
| bis(diphenylphosphino)amines-containing ruthenium cymene complexes as potential anti-mycobacterium tuberculosis agents. | several ruthenium complexes have been investigated regarding anti-mycobacterium tuberculosis (anti-mtb) activity, with some diphosphine-containing ruthenium complexes comparable to first and second line drugs. however, to the best of our knowledge, there is no pnp-containing ruthenium complexes applied as metallodrugs. thus, this study focused on the synthesis, characterization and anti-mtb activity of a new series of coordination compounds with general formula [rucl(η(6)-p-cymene)(pn(r)p)]x (r= ... | 2017 | 28521188 |
| the changing epidemiology of spinal tuberculosis: the influence of international immigration in catalonia, 1993-2014. | the overall incidence of spinal tuberculosis (tb) appears to be stable or declining in most european countries, but with an increasing proportion of cases in the foreign-born populations. we performed a retrospective observational study (1993-2014), including all cases of spinal tb diagnosed at a barcelona hospital to assess the epidemiological changes. fifty-four episodes (48·1% males, median age 52 years) of spinal tb were diagnosed. the percentage of foreign-born residents with spinal tb incr ... | 2017 | 28516818 |
| the history of tuberculosis: from the first historical records to the isolation of koch's bacillus. | tuberculosis (tb) is a contagious, infectious disease, due to mycobacterium tuberculosis (mt) that has always been a permanent challenge over the course of human history, because of its severe social implications. it has been hypothesized that the genus mycobacterium originated more than 150 million years ago. in the middle ages, scrofula, a disease affecting cervical lymph nodes, was described as a new clinical form of tb. the illness was known in england and france as "king's evil", and it was ... | 2017 | 28515626 |
| characterization of a secretory hydrolase from mycobacterium tuberculosis sheds critical insight into host lipid utilization by m. tuberculosis. | mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. to survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. for example, m. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. m. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question aris ... | 2017 | 28515317 |
| pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immunopathogenesis: emerging concepts and perspectives. | pattern recognition receptors (prrs) play a central role in the recognition of numerous pathogens, including mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. besides toll like receptors, c-type lectin receptors and nod like receptors are now being recognized for their involvement in inducing immune response against m. tuberculosis infection. although, a functional redundancy of the prrs has also been reported in many studies, emerging evidences support ... | 2017 | 28514713 |
| evaluation of improved is6110 lamp assay for diagnosis of pulmonary and extra pulmonary tuberculosis. | in the present study, is6110 loop mediated isothermal amplification (lamp) assay was modified using dutp-ung (uracil-dna n-glycosylase) strategy to prevent carryover contamination, and was evaluated using clinical specimens. the clinical specimens were collected from 236 suspected patients of pulmonary tuberculosis and 315 specimens of suspected patients of extra pulmonary tuberculosis. dna was extracted from specimens and used as template for nucleic acid amplification. the results were evaluat ... | 2017 | 28514671 |
| fragment screening against the ethr-dna interaction by native mass spectrometry. | native nanoelectrospray ionization mass spectrometry is an underutilized technique for fragment screening. in this study, the first demonstration is provided of the use of native mass spectrometry for screening fragments against a protein-dna interaction. ethr is a transcriptional repressor of etha expression in mycobacterium tuberculosis (mtb) that reduces the efficacy of ethionamide, a second-line antitubercular drug used to combat multidrug-resistant mtb strains. a small-scale fragment screen ... | 2017 | 28513917 |
| clinical and bacteriological characteristics associated with clustering of multidrug-resistant tuberculosis. | the impact of the genetic characteristics of mycobacterium tuberculosis on the clustering of multidrug-resistant tuberculosis (mdr-tb) has not been analyzed together with clinical and demographic characteristics. | 2017 | 28513421 |
| the role of esx-1 in mycobacterium tuberculosis pathogenesis. | in this article, we have described several cellular pathological effects caused by the mycobacterium tuberculosis esx-1. the effects include induction of necrosis, nod2 signaling, type i interferon production, and autophagy. we then attempted to suggest that these pathological effects are mediated by the cytosolic access of m. tuberculosis-derived materials as a result of the phagosome-disrupting activity of the major esx-1 substrate esat-6. such activity of esat-6 is most likely due to its pore ... | 2017 | 28513416 |
| effect of trichilia monadelpha (meliaceae) extracts on bone histomorphology in complete freund's adjuvant-induced arthritis. | this study aimed to assess the effect of petroleum ether extract (pee), ethyl acetate extract (ethe), and ethanol extract (eae) of trichilia monadelpha stem bark on bone histomorphology in arthritis. | 2017 | 28512599 |
| synthesis, antimycobacterial activity and docking study of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1h)-one derivatives and related hydrazide-hydrazones. | a new convenient method for preparation of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1h)-one derivatives 5b-g and coumarin containing hydrazide-hydrazone analogues 4a-e was presented. the antimycobacterial activity against reference strain mycobacterium tuberculosis h37rv and cytotoxicity against the human embryonic kidney cell line hek-293 were tested in vitro. all compounds demonstrated significant minimum inhibitory concentrations (mic) ranging 0.28-1.69μm, which were comparable to those of ison ... | 2017 | 28512022 |
| diagnostic performance of anyplex ii mtb/mdr/xdr for detection of resistance to first and second line drugs in mycobacterium tuberculosis. | genotypic methods have considerably improved the diagnosis of multidrug-resistant (mdr) tuberculosis. one of these tests is anyplex ii mtb/mdr/xdr (anyplex). our aim was to evaluate the diagnostic performance of this multiplex pcr. | 2017 | 28511895 |
| sputum microscopy with fluorescein diacetate predicts tuberculosis infectiousness. | sputum from patients with tuberculosis contains subpopulations of metabolically active and inactive mycobacterium tuberculosis with unknown implications for infectiousness. | 2017 | 28510693 |
| conjugation reaction with 8-arm peg markedly improves the immunogenicity of mycobacterium tuberculosis cfp10-tb10.4 fusion protein. | mycobacterium tuberculosis (mtb) is a serious fatal pathogen responsible for tuberculosis (tb). effective vaccination is highly desired for immunoprotection against mtb infection. cfp10 and tb10.4 are two important immunodominant mtb-secreted protein antigens, which suffer from poor immunogenicity. thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. a cfp10-tb10.4 fusion protein (ct) was used as the antigen in the present study. conjugatio ... | 2017 | 28510418 |
| the phytochemical bergenin enhances t helper 1 responses and anti-mycobacterial immunity by activating the map kinase pathway in macrophages. | tuberculosis (tb) remains one of the greatest health concerns worldwide, which has hindered socioeconomic development in certain parts of the world for many centuries. although current tb therapy, "directly observed treatment short-course," is effective, it is associated with unwanted side effects and the risk for the generation of drug-resistant organisms. the majority of infected individuals successfully confine the mycobacterial organisms and remain asymptotic unless immune responses are pert ... | 2017 | 28507951 |
| the mycobacterium tuberculosis mmpl11 cell wall lipid transporter is important for biofilm formation, intracellular growth, and nonreplicating persistence. | the mycobacterial cell wall is crucial to the host-pathogen interface, because it provides a barrier against antibiotics and the host immune response. in addition, cell wall lipids are mycobacterial virulence factors. the mycobacterial membrane protein large (mmpl) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and mycobacterium tuberculosis pathogenesis. mmpl3 and mmpl11 are conserved across pathogenic and nonpathogenic mycobacteria, a feature co ... | 2017 | 28507063 |
| chloroquine enhances the antimycobacterial activity of isoniazid and pyrazinamide by reversing inflammation-induced macrophage efflux. | mycobacterium tuberculosis (mtb) is notorious for persisting within host macrophages. efflux pumps decrease intracellular drug levels, thus fostering persistence of mtb during therapy. isoniazid (inh) and pyrazinamide (pza) are substrates of the efflux pump breast cancer resistance protein-1 (bcrp-1), which is inhibited by chloroquine (cq). in this study, bcrp-1 was found to be expressed on macrophages of human origin and on foamy giant cells at the site of mtb infection. in the current in vitro ... | 2017 | 28506804 |
| comparison of antibody responses against mycobacterium tuberculosis antigen rv0679c in tuberculosis patients from the endemic and non-endemic regions of the beijing genotype: a case control study. | strains of the beijing genotype of mycobacterium tuberculosis (mtb) are reportedly associated with the virulence of tuberculosis (tb) infection, unfavorable outcomes of anti-tb treatment, and the global tb pandemic. rv0679c, a hypothetical membrane protein related to host cell invasion, has a beijing genotype-specific mutation at residue 142 (asn142lys). antigenicity differences between rv0679c-asn142 (n-type) and rv0679c-lys142 (k-type) have been previously observed in mice antigen-antibody res ... | 2017 | 28506215 |
| systematic, multiparametric analysis of mycobacterium tuberculosis intracellular infection offers insight into coordinated virulence. | a key to the pathogenic success of mycobacterium tuberculosis (mtb), the causative agent of tuberculosis, is the capacity to survive within host macrophages. although several factors required for this survival have been identified, a comprehensive knowledge of such factors and how they work together to manipulate the host environment to benefit bacterial survival are not well understood. to systematically identify mtb factors required for intracellular growth, we screened an arrayed, non-redunda ... | 2017 | 28505176 |
| antitubercular activity of mycelium-associated ganoderma lanostanoids. | in a continuation of our research into antitubercular lanostane triterpenoids from submerged cultures of ganoderma species, three strains, ganoderma orbiforme bcc 22325, ganoderma sp. bcc 60695, and ganoderma australe bcc 22314, have been investigated. fourteen new lanostane triterpenoids, together with 35 known compounds, were isolated. antitubercular activities of these mycelium-associated ganoderma lanostanoids against mycobacterium tuberculosis h37ra were evaluated. taken together with the a ... | 2017 | 28504879 |
| nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. | nitric oxide contributes to protection from tuberculosis. it is generally assumed that this protection is due to direct inhibition of mycobacterium tuberculosis growth, which prevents subsequent pathological inflammation. in contrast, we report that nitric oxide primarily protects mice by repressing an interleukin-1- and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes bacterial replication. using m. tuberculosis mutants as indicators of the pathogen's environment, we in ... | 2017 | 28504669 |
| commentary: modification of host responses by mycobacteria. | | 2017 | 28503174 |
| humanized nog mice as a model for tuberculosis vaccine-induced immunity: a comparative analysis with the mouse and guinea pig models of tuberculosis. | the humanized mouse model has been developed as a model to identify and characterize human immune responses to human pathogens and has been used to better identify vaccine candidates. in the current studies, the humanized mouse was used to determine the ability of a vaccine to affect the immune response to infection with mycobacterium tuberculosis. both human cd4(+) and cd8(+) t cells responded to infection in humanized mice as a result of infection. in humanized mice vaccinated with either bcg ... | 2017 | 28502122 |
| molecular detection of rifampicin resistance by genexpert(®) assay among treated and untreated pulmonary tuberculosis patients from khyber pakhtunkhwa, pakistan. | drug-resistant tuberculosis (tb) is an emerging health problem. rifampicin (rif) is the major first-line drug against tb. rif resistance can be used as a marker for the detection of multidrug-resistant tb (mdr-tb). the purpose of this study was to determine the rif resistance pattern of mycobacterium tuberculosis complex isolates among treated and untreated patients in khyber pakhtunkhwa, pakistan. | 2017 | 28501582 |
| tuberculosis in liver transplant recipients: a report of eight cases during a five year period. | tuberculosis incidence in portugal ranged from 20 to 22 cases per 100 000 inhabitants between 2010 and 2014. tuberculosis incidence in liver transplant recipients is not precisely known, but it is estimated to be higher than among the general population. tuberculosis in liver transplant recipients is particularly challenging because of the atypical clinical presentation and side effects of the antibacillary drugs and their potential interactions with immunosuppressive therapies. | 2017 | 28501036 |
| first insight into the fluoroquinolone and aminoglycoside resistance of multidrug-resistant mycobacterium tuberculosis in saudi arabia. | abstractin saudi arabia, there were no nationwide screening studies conducted so far to determine the aminoglycoside and fluoroquinolone resistance among multidrug-resistant tuberculosis (mdr-tb) isolates. therefore, as the first attempt in the country, a retrospective analysis has been conducted on a nationwide collection of 2,956 m. tuberculosis clinical isolates screened with phenotypic drug susceptibility testing to define mdr-tb. enrolled mdr-tb isolates were subjected to second-line drug s ... | 2017 | 28500800 |
| structural and mechanistic insights into mycothiol disulphide reductase and the mycoredoxin-1-alkylhydroperoxide reductase e assembly of mycobacterium tuberculosis. | mycobacteria employ a versatile machinery of the mycothiol-dependent system, containing the proteins mycothiol disulfide reductase (mtr), the oxido-reductase mycoredoxin-1 (mrx-1) and the alkyl-hydroperoxide subunit e (ahpe). the mycothiol-dependent protein ensemble regulates the balance of oxidized-reduced mycothiol, to ensure a reductive intracellular environment for optimal functioning of its proteins even upon exposure to oxidative stress. here, we determined the first low-resolution solutio ... | 2017 | 28499823 |
| cystic fibrosis carriership and tuberculosis: hints toward an evolutionary selective advantage based on data from the brazilian territory. | the reason why cystic fibrosis (cf) is the most common fatal genetic disease among caucasians has been incompletely studied. we aimed at deepening the hypothesis that cf carriers have a relative protection against mycobacterium tuberculosis (mtb) infection. | 2017 | 28499359 |
| mycobacterium tuberculosis whole genome sequences from southern india suggest novel resistance mechanisms and the need for region-specific diagnostics. | india is home to 25% of all tuberculosis cases and the second highest number of multidrug resistant cases worldwide. however, little is known about the genetic diversity and resistance determinants of indian mycobacterium tuberculosis, particularly for the primary lineages found in india, lineages 1 and 3. | 2017 | 28498943 |
| safety and immunogenicity of an inactivated whole cell tuberculosis vaccine booster in adults primed with bcg: a randomized, controlled trial of dar-901. | development of a tuberculosis vaccine to boost bcg is a major international health priority. srl172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a phase 3 trial. in the present study we sought to determine if a three-dose series of dar-901 manufactured from the srl172 master cell bank by a new, scalable method was safe and immunogenic. | 2017 | 28498853 |
| natural and synthetic flavonoids as potent mycobacterium tuberculosis ugm inhibitors. | this study reports a novel class of inhibitors of uridine 5'-diphosphate (udp) galactopyranose mutase (ugm) derived from a screening of natural products. this enzyme is an essential biocatalyst involved in the cell wall biosynthesis of mycobacterium tuberculosis. flavonoids are potent inhibitors of ugm. the synthesis of novel methylated flavonoids allowed a structure-activity relationship analysis to be performed and which functional groups and structural elements were required for ugm inhibitio ... | 2017 | 28497493 |
| bortezomib warhead-switch confers dual activity against mycobacterial caseinolytic protease and proteasome and selectivity against human proteasome. | mycobacteria harbor two main degradative proteolytic machineries, the caseinolytic protease clpp1p2 and a proteasome. we recently showed that bortezomib inhibits clpp1p2 and exhibits whole cell activity against mycobacterium tuberculosis. bortezomib, a dipeptide with a boronic acid warhead, is a human proteasome inhibitor approved for cancer therapy. the boronic acid warhead of the compound has been shown to drive potency against both the human proteasome and clpp1p2 protease. selectivity for th ... | 2017 | 28496439 |