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qsar, docking studies of 1,3-thiazinan-3-yl isonicotinamide derivatives for antitubercular activity.the enzyme - enoyl acyl carrier protein reductase (enoyl acp reductase) is a validated target for antitubercular activity. inhibition of this enzyme interferes with mycolic acid synthesis which is crucial for mycobacterium tuberculosis cell growth. in the present work 2d and 3d quantitative structure activity relationship (qsar) studies were carried out on a series of thiazinan-isoniazid pharmacophore to design newer analogues. for 2d qsar, the best statistical model was generated using sa-mlr m ...201728411471
synthesis and immunogenicity of pg-tb1 monovalent glycoconjugate.a pg-tb1 hapten from the west beijing strains of mycobacterium tuberculosis cell wall has been efficiently synthesized and conjugated to crm197 in a simple way as linker-equipped carbohydrate by applying squaric acid chemistry for an original neoglycoprotein, creating a potent t-dependent conjugate vaccine. the intermediate monoester can be easily purified and the degree of incorporation can be monitored by maldi-tof mass spectrometry. after administered systemically in mice without any adjuvant ...201728411454
detection of pyrazinamide resistance of mycobacterium tuberculosis using nicotinamide as a surrogate.despite the importance of pyrazinamide (pza) in tuberculosis treatment, pza susceptibility testing is not routinely performed because of its acid ph requirement. we evaluated the microplate alamar blue assay (maba) to detect resistance to pza using nicotinamide (nic) as a surrogate in neutral ph and identify the appropriate cutoff point for the assay.201728411185
multifocal pure tubercular osteomyelitis: an unusual presentation in childhood.tuberculosis is a major health problem in the developing world. one-third of children infected with mycobacterium tuberculosis have extra pulmonary involvement. skeletal tuberculosis occurs in 1-6% of them with vertebra being the commonest site. pure tubercular osteomyelitis without joint involvement occurs in only 2-3% cases of osteoarticular tuberculosis. common sites are femur, tibia, and fibula. disseminated skeletal involvement is very rare in children (7%) and calvarial osteomyelitis is ev ...201728410697
pyridines: multidrug-resistant tuberculosis (mdr-tb) inhibitors.mycobacterium tuberculosis (mtb) infection has become an increasing health threat due to the worldwide emergence of multidrug-resistant mtb (mdr-mtb) strain. isoniazid (pyridine) resistance problem is a complex process and is associated with mutations in several genes. however, the emergence of isoniazid (inh) resistant m. tuberculosis strains dictates the necessity for redesigning this old drug in order to create analogs effective against inh-resistant strains by using rational approach. in lig ...201728410694
diallyl polysulfides from allium sativum as immunomodulators, hepatoprotectors, and antimycobacterial agents.mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. the medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. the current study evaluated the efficacy of six allium sativum l. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. the microtitre prestoblue assay was used to determine t ...201728410455
treatment of latent tuberculosis infection.there are approximately 56 million people who harbor mycobacterium tuberculosis that may progress to active tuberculosis (tb) at some point in their lives. modeling studies suggest that if only 8% of these individuals with latent tb infection (ltbi) were treated annually, overall global incidence would be 14-fold lower by 2050 compared to incidence in 2013, even in the absence of additional tb control measures. this highlights the importance of identifying and treating latently infected individu ...201728409555
use of video directly observed therapy for treatment of latent tuberculosis infection - johnson county, kansas, 2015.tuberculosis (tb) is caused by the bacterium mycobacterium tuberculosis and is spread from person to person through the air. tb can be spread in congregate settings, such as school environments, to varying degrees, based on factors including duration of contact and air ventilation (1); therefore, evaluating potential contacts and exposures can be challenging. in february 2015, a student at a kansas high school received a diagnosis of active pulmonary tb disease. screening of 385 (91%) school con ...201728406884
increased tuberculosis patient mortality associated with mycobacterium tuberculosis mutations conferring resistance to second-line antituberculous drugs.rapid molecular diagnostics have great potential to limit the spread of multidrug-resistant tuberculosis (mdr-tb) and extensively drug-resistant tuberculosis (xdr-tb) (m/xdr-tb). these technologies detect mutations in the mycobacterium tuberculosis genome that confer phenotypic drug resistance. however, there have been few data published regarding the relationships between the detected m. tuberculosis resistance mutations and m/xdr-tb treatment outcomes, limiting our current ability to exploit t ...201728404672
frequency of rrs and rpsl mutations in streptomycin-resistant mycobacterium tuberculosis isolates from iranian patients.streptomycin (sm) is one of the most effective drugs for the treatment of multidrug-resistant (mdr) tuberculosis. however, resistance to sm is increasingly reported, mainly due to mutations in the rpsl and rrs genes. this study was designed with the aim of determining the nature of sm resistance and the type and frequency of rpsl and rrs mutations among sm-resistant mycobacterium tuberculosis (mtb) isolates from iran.201728404234
molecular detection of drug resistance to ofloxacin and kanamycin in mycobacterium tuberculosis by using multiplex allele-specific pcr.drug resistance in tuberculosis (tb) is the biggest global health challenge as it hinders the tuberculosis control program and makes the disease more worsen. molecular methods interrupt the spread of drug resistance by facilitating the appropriate anti- tuberculosis therapy at correct time through rapid diagnosis of multi drug resistant (mdr) and extensively drug resistant tuberculosis (xdr-tb). in this study we standardized and evaluated the diagnostic utility of multiplex allele specific pcr ( ...201728404233
tuberculosis among prison staff in rio grande do sul.to evaluate the risk of infection and illness caused by mycobacterium tuberculosis among health care and security staff in prisons in two regions of rio grande do sul (rs).201728403282
association of vitamin d deficiency, season of the year, and latent tuberculosis infection among household contacts.vitamin d (vd) enhances the immune response against mycobacterium tuberculosis in vitro, and vd deficiency has been described in patients with active tuberculosis (tb). however, the role of hypovitaminosis d in the pathogenesis of early tb infection acquisition is unclear. we aimed to evaluate the association of vd deficiency, season of the year, and latent tb infection in household contacts (hhc), given that this is a potentially modifiable condition often related to nutritional deficiencies an ...201728403225
the risk of mycobacterium tuberculosis transmission from pediatric index cases to school pupils.this study is the largest report on mycobacterium tuberculosis transmission rate (tr) from children with pulmonary tuberculosis to school pupils. higher tr (around 21.6%) was observed in contacts of smear-positive children. tr from pediatric smear-negative index cases was around 0. if our data are confirmed, school contacts of a smear-negative index case could be screened only by clinical evaluation and tuberculin skin test, avoiding the routine use of chest radiographs in children less than 5 y ...201728403060
bcl-xl mediates ripk3-dependent necrosis in m. tuberculosis-infected macrophages.virulent mycobacterium tuberculosis (mtb) triggers necrosis in host mϕ, which is essential for successful pathogenesis in tuberculosis. here we demonstrate that necrosis of mtb-infected mϕ is dependent on the action of the cytosolic receptor interacting protein kinase 3 (ripk3) and the mitochondrial bcl-2 family member protein b-cell lymphoma-extra large (bcl-xl). ripk3-deficient mϕ are able to better control bacterial growth in vitro and in vivo. mechanistically, cytosolic ripk3 translocates to ...201728401933
tuberculosis in children with sickle cell anaemia: a retrospective study in french tertiary care centres.tuberculosis (tb) and sickle cell anaemia (sca) may affect the same population of patients, particularly in africa but also in high-tb incidence areas in developed countries. however, few data are available from children with sca who develop tb. the aim of this study was to describe the clinical features and outcome of tb diagnosed in children with sca. we conducted a retrospective, descriptive study in three referral centre of sickle cell disease in paris, france. we included 11 patients with s ...201728401342
nontuberculous mycobacterial infection of the musculoskeletal system in immunocompetent hosts.nontuberculous mycobacteria (ntm) were considered saprophytic organisms for many years but now are recognized as human pathogens. although humans are routinely exposed to ntm, the rate of clinical infection is low. such infections usually occur in the elderly and in patients who are immunocompromised. however, there has been an increasing incidence in recent years of infections in immunocompetent hosts. ntm infections in immunocompetent individuals are secondary to direct inoculation either cont ...201728400668
targeting energy metabolism in mycobacterium tuberculosis, a new paradigm in antimycobacterial drug discovery.drug-resistant mycobacterial infections are a serious global health challenge, leading to high mortality and socioeconomic burdens in developing countries worldwide. new innovative approaches, from identification of new targets to discovery of novel chemical scaffolds, are urgently needed. recently, energy metabolism in mycobacteria, in particular the oxidative phosphorylation pathway, has emerged as an object of intense microbiological investigation and as a novel target pathway in drug discove ...201728400527
type-1 polarised dendritic cells are a potent immunogen against mycobacterium tuberculosis.application of immunotherapy using dendritic cells (dcs) is considered an effective treatment strategy against persistent mycobacterium tuberculosis infection. with the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (tb), we tested the ability of ex vivo-generated dcs to induce an effective tb antigen-specific type-1 immune response.201728399967
impact of euro-american sublineages of mycobacterium tuberculosis on new infections among named contacts.the impact of demographic, clinical, and bacterial factors on new infection by euro-american lineage mycobacterium tuberculosis among contacts of patients with tuberculosis (tb) has not been evaluated.201728399965
pooling sputum samples to improve the feasibility of xpert(®) mtb/rif in systematic screening for tuberculosis.systematic screening for tuberculosis (tb) using xpert® mtb/rif.201728399964
tuberculosis of the glans penis: an important differential diagnosis of genital ulcer disease.we report a 45-year-old, apparently healthy sero-negative man, presenting with multiple ulcers on the glans penis for a duration of three months. there was no significant inguinal lymphadenopathy. he showed no improvement on systemic antibiotics and acyclovir. histopathology revealed the diagnosis of genital tuberculosis (tb), and polymerase chain reaction for mycobacterium tuberculosis tested positive. the patient responded well to category i anti-tubercular treatment with complete resolution o ...201728399708
nicotine impairs macrophage control of mycobacterium tuberculosis.pure nicotine impairs macrophage killing of mycobacterium tuberculosis (mtb) but it is not known whether the nicotine component in cigarette smoke (cs) plays a role. moreover, the mechanisms by which nicotine impairs macrophage immunity against mtb have not been explored. to neutralize the effects of nicotine in cs extract, we utilized a competitive inhibitor to the nicotinic acetylcholine receptor (nachr) - mecamylamine - as well as macrophages derived from mice with genetic disruption of speci ...201728398760
drug resistance in newly presenting and previously treated tuberculosis patients in guangxi province, people's republic of china.drug-resistant mycobacterium tuberculosis strains are a major threat to the control of tuberculosis (tb), but the prevalence of drug-resistant tb is still unknown in the southern ethnic region of china. a cluster-randomized sampling method was used to include the study population. isolates were tested for resistance to 6 antituberculosis drugs, and genotyped to identify beijing strains. overall, 11.3% (139/1229) of new cases and 33.0% (126/382) of retreated cases had drug-resistant tuberculosis. ...201728397531
the activity of a hexameric m17 metallo-aminopeptidase is associated with survival of mycobacterium tuberculosis.mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. moreover, tuberculosis (tb) treatment has become increasingly challenging owing to the emergence of multidrug resistant m. tuberculosis strains. thus, there is an immediate need for the development of new anti-tb drugs. proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant tb. although the m. tuberculosis genome predicts ...201728396657
enhanced respiration prevents drug tolerance and drug resistance in mycobacterium tuberculosis.persistence, manifested as drug tolerance, represents a significant obstacle to global tuberculosis control. the bactericidal drugs isoniazid and rifampicin kill greater than 99% of exponentially growing mycobacterium tuberculosis (mtb) cells, but the remaining cells are persisters, cells with decreased metabolic rate, refractory to killing by these drugs, and able to generate drug-resistant mutants. we discovered that the combination of cysteine or other small thiols with either isoniazid or ri ...201728396391
[application of the bacspreader™ microbe dispersion counter in drug susceptibility test on mycobacterium tuberculosis].objective: to evaluate the application of the bacspreader™ microbe dispersion counter in drug susceptibility test (dst) on mycobacterium tuberculosis (mtb). methods: the mtb strains were dispersed and diluted to 1.0 mcfarland standard turbidity, by means of bacspreader™ microbe dispersion counter and manual grinding method, respectively. the bacterial dispersion effect and bacterial activity were tested by microscope and colony counting method. during jan. 2015 to june 2015, a total of 726 isola ...201728395409
an opposing view on including high school students in a latent tuberculosis infection control program in korea.the korea centers for diseases control and prevention (kcdc) has announced a control program against latent mycobacterium tuberculosis infection (ltbi), for a "tb-safe country" this year with the goal of a "tb-free korea" by 2025. the program includes high school students as one target group; however, some school health teachers and parents have expressed their opposition to this. the 2015 world health organization guidelines do not recommend inclusion of asymptomatic high school students in ltb ...201728395400
genomic analyses of the ancestral manila family of mycobacterium tuberculosis.with its airborne transmission and prolonged latency period, mycobacterium tuberculosis spreads worldwide as one of the most successful bacterial pathogens and continues to kill millions of people every year. m. tuberculosis lineage 1 is inferred to originate ancestrally based on the presence of the 52-bp tbd1 sequence and analysis of single nucleotide polymorphisms. previously, we briefly reported the complete genome sequencing of m. tuberculosis strains 96121 and 96075, which belong to the anc ...201728394899
18f-fdg pet/ct of tuberculosis meningitis and carotid pseudoaneurysm.a 26-year-old woman presented with a headache, left-sided weakness of the body, and pulsatile swelling above the sternal notch. she was treated for abdominal tuberculosis in the past, two years later she developed miliary tuberculosis and was put on modified regimen of antitubercular drugs in view of drug induced hepatitis. ultrasound neck revealed saccular aneurysm measuring 4 x 3 cm, located in between common carotid arteries with an eccentric thrombus. mri brain revealed multiple tuberculoma ...201728394836
structure of the mycobacterial esx-5 type vii secretion system membrane complex by single-particle analysis.mycobacteria are characterized by their impermeable outer membrane, which is rich in mycolic acids(1). to transport substrates across this complex cell envelope, mycobacteria rely on type vii (also known as esx) secretion systems(2). in mycobacterium tuberculosis, these esx systems are essential for growth and full virulence and therefore represent an attractive target for anti-tuberculosis drugs(3). however, the molecular details underlying type vii secretion are largely unknown, due to a lack ...201728394313
association of c-type lectin mincle with fcεriβγ subunits leads to functional activation of rbl-2h3 cells through syk.macrophage-inducible c-type lectin (mincle) interacts with the γ-subunit of high-affinity ige receptor (fcεriγ) and activates syk by recognizing its specific ligand, trehalose-6,6'-dimycolate, a glycolipid produced by mycobacterium tuberculosis. it has been suggested that mast cells participate in the immune defense against pathogenic microbes including m. tuberculosis, although the functions are still uncertain. in this study, we examined the mincle-mediated signaling pathway and cellular respo ...201728393919
improving basic and membrane protein ms detection of the culture filtrate proteins from mycobacterium tuberculosis h37rv by biomimetic affinity pre-fractionation.the culture filtrate proteins (cfps) from mycobacterium tuberculosis (mtb) have been shown to induce protective immune responses in human and animal models, making them a promising source of candidate targets for tuberculosis drugs, vaccines and diagnostics. the constituents of the mtb cfp proteome are complex and vary with growth conditions. to effectively profile cfps, gel-based pre-fractionation is usually performed before ms analysis. in this study, we describe a novel pre-fractionation appr ...201728393466
early diagnosis of tuberculosis-associated iga nephropathy with esat-6.iga nephropathy (igan) is the most common cause of primary renal diseases worldwide, and the early secreted antigenic target of 6 (esat-6) which was secreted by mycobacterium tuberculosis (mtb) may be involved in the development and progression of igan. this study aimed to investigate the role of esat-6 for early diagnosis of igan caused by mtb infection. from 2011 to 2014, 21 patients with renal tuberculosis (rtb), 25 with igan, and 46 with igan infected with mtb (igan/mtb) were enrolled. serum ...201728392505
anti-inflammatory, antimycobacterial and genotoxic evaluation of doliocarpus dentatus.doliocarpus dentatus is a medicinal plant widely used in mato grosso do sul state for removing the swelling pain caused by the inflammation process and for treating urine retention.201728392458
prevalence of latent mycobacterium tuberculosis infection (ltbi) in saudi arabia; population based survey.the annual risk of tuberculosis infection (arti) data in saudi arabia has not been updated since 1993.201728392316
hybrid mass spectrometry approaches to determine how l-histidine feedback regulates the enzyzme mtatp-phosphoribosyltransferase.mtatp-phosphoribosyltransferase (mtatp-prt) is an enzyme catalyzing the first step of the biosynthesis of l-histidine in mycobacterium tuberculosis, and proposed to be regulated via an allosteric mechanism. native mass spectrometry (ms) reveals mtatp-prt to exist as a hexamer. conformational changes induced by l-histidine binding and the influence of buffer ph are determined with ion mobility ms, hydrogen deuterium exchange (hdx) ms, and analytical ultracentrifugation. the experimental collision ...201728392260
structural basis of mycobacterium tuberculosis transcription and transcription inhibition.mycobacterium tuberculosis (mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. mtb rna polymerase (rnap) is the target of the first-line antituberculosis drug rifampin (rif). we report crystal structures of mtb rnap, alone and in complex with rif, at 3.8-4.4 å resolution. the results identify an mtb-specific structural module of mtb rnap and establish that rif functions by a steric-occlusion mechanism that prevents extension of rna. we also report non-rif-related comp ...201728392175
lung tissue concentrations of pyrazinamide among patients with drug-resistant pulmonary tuberculosis.improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass ...201728373198
stratification of latent mycobacterium tuberculosis infection by cellular immune profiling.recently acquired and remotely acquired latent mycobacterium tuberculosis infection (ltbi) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to tuberculosis in immunocompetent individuals. we aimed to evaluate the ability of cellular immune signatures that differ between active tuberculosis and ltbi to distinguish recently from remotely acquired ltbi.201728329119
evaluation of quantiferon-tb gold-plus in health care workers in a low-incidence setting.although launched in 2015, little is known about the accuracy of quantiferon-tb gold-plus (qft-plus) for diagnosis of latent m. tuberculosis infection (ltbi). unlike its predecessor, qft-plus utilizes two antigen tubes to elicit an immune response from cd4(+) and cd8(+) t lymphocytes. we conducted a cross-sectional study in low-risk health care workers (hcws) at a single u.s. center to compare qft-plus to quantiferon-tb gold in-tube (qft). a total of 989 hcws were tested with both qft and qft-pl ...201728298455
concentration-dependent antagonism and culture conversion in pulmonary tuberculosis.there is scant evidence to support target drug exposures for optimal tuberculosis outcomes. we therefore assessed whether pharmacokinetic/pharmacodynamic (pk/pd) parameters could predict 2-month culture conversion.201728205671
oxidative stress and tb outcomes in patients with diabetes mellitus?in patients with diabetes mellitus, tb treatment outcomes are poorer. most parameters, when measured, reflect the slower bacteriological conversion from positivity to negativity and higher risks of disease relapse and mortality, as well as a greater propensity to develop drug-resistant tb. aside from the well-known immunological dysfunction inherent to patients with diabetes mellitus, oxidative stress is likely a major underlying mechanism adversely impacting their tb treatment outcomes. mycobac ...201728204508
interaction of rifampin and darunavir-ritonavir or darunavir-cobicistat in vitro.treatment of hiv-infected patients coinfected with mycobacterium tuberculosis is challenging due to drug-drug interactions (ddis) between antiretrovirals (arvs) and antituberculosis (anti-tb) drugs. the aim of this study was to quantify the effect of cobicistat (cobi) or ritonavir (rtv) in modulating ddis between darunavir (drv) and rifampin (rif) in a human hepatocyte-based in vitro model. human primary hepatocyte cultures were incubated with rif alone or in combination with either cobi or rtv ...201728193650
clinical impact and cost-effectiveness of xpert mtb/rif testing in hospitalized patients with presumptive pulmonary tuberculosis in the united states.microscopic examination of acid-fast-stained sputum smears is the current standard of care in the united states to determine airborne infection isolation (aii) of inpatients with presumptive pulmonary tuberculosis (ptb). however, nucleic acid amplification testing (naat) with the xpert mtb/rif assay (xpert) may be more efficient and less costly.201728172666
profile of tuberculous cervical lymphadenopathy in children.analyze clinical profile of tuberculous cervical lymphadenopathy in children.201728158382
effect of pregnancy on interferon gamma release assay and tuberculin skin test detection of latent tb infection among hiv-infected women in a high burden setting.peripartum immunologic changes may affect latent tuberculosis infection (ltbi) diagnostic performance among hiv-infected women.201728141782
tackling drug-resistant tuberculosis: current trends and approaches.tuberculosis is very much rampant in our society and accounts for a large number of deaths annually. in spite of consistent efforts being made, the disease has not been curtailed yet. the emergence of mdr and xdr strains in the society along with an increase in the number of hiv cases and that of latent tb, have further aggravated the problem making the disease very much persistent. the current situation clearly manifests the need to discover and develop new potent molecules/approaches that coul ...201727280980
cell wall associated factors of mycobacterium tuberculosis as major virulence determinants: current perspectives in drugs discovery and design.mycobacteria genus is responsible for deadly diseases like tuberculosis and leprosy. cell wall of bacteria belonging to this genus is unique in many ways. it plays a major role in pathogenesis and intracellular survival inside the host. in intracellular pathogens, their cell wall acts as molecular shield and interacts with host cell milieu to modulate host defense responses. unique role of cell wall associated factors that play crucial roles in the biosynthesis of mycobacterial cell wall compone ...201728699515
tuberculosis in kidney transplant recipients: a case series.solid organ transplant recipients have an elevated risk of tuberculosis (tb) with high mortality. data about tb in this population in the united states is sparse. we present four cases of active tuberculosis in kidney transplant recipients at our center. all patients had possible tb exposure prior to transplant and all were diagnosed with active tb within the first year of transplant. disseminated tb was seen in half of the patients with extra-pulmonary tb being more common affecting lymph nodes ...201728698838
antigens rv0310c and rv1255c are promising novel biomarkers for the diagnosis of mycobacterium tuberculosis infection.this study aimed to identify novel immunogenic epitopes from mycobacterium tuberculosis (mtb) that could be used in tuberculosis (tb) diagnostics. to determine the diagnostic potential of mycobacterial antigens in serodiagnosis of tb, 256 patients were enrolled in a study and divided into two groups: 126 smear-positive pulmonary tb patients (sppt) and 130 smear-negative pulmonary tb patients (snpt); 152 bacillus calmette-guerin (bcg)-vaccinated healthy people were used as a control. murine resul ...201728698665
a novel protein kinase inhibitor imb-yh-8 with anti-tuberculosis activity.protein kinase b (pknb) is one of the mycobacterium tuberculosis serine/threonine protein kinases and has an essential role in sustaining mycobacterial growth. here, we identified and characterized a novel small molecule compound named imb-yh-8 that inhibited pknb and served as anti-mycobacteria lead compound. imb-yh-8 inhibited pknb auto-phosphorylation and the phosphorylation of gara by pknb in a dose-dependent manner. the compound did not inhibit human akt1 or other serine/threonine kinases i ...201728698545
multidrug-resistant/extensively drug-resistant tuberculosis in greece: predominance of mycobacterium tuberculosis genotypes endemic in the former soviet union countries. 201728698038
pyrazinamide resistance-conferring mutations in pnca and the transmission of multidrug resistant tb in georgia.the ongoing epidemic of multidrug-resistant tuberculosis (mdr-tb) in georgia highlights the need for more effective control strategies. a new regimen to treat mdr-tb that includes pyrazinamide (pza) is currently being evaluated and pza resistance status will largely influence the success of current and future treatment strategies. pza susceptibility testing was not routinely performed at the national reference laboratory (nrl) in tbilisi between 2010 and september 2015. we here provide a first i ...201728697808
plumbago auriculata leaf extract-mediated agnps and its activities as antioxidant, anti-tb and dye degrading agents.in the present work, silver nanoparticles have been biosynthesized by utilizing the alcoholic extract of plumbago auriculata. the optimization of reaction conditions was carried out by monitoring the reactions with the help of uv-visible absorption spectroscopy. the characterization of agnp was carried out by infrared spectroscopy, transmission electron microscopy and x-ray diffraction (xrd) studies. the biogenic agnps were tested against mycobacterium tuberculosis using microplate almar blue as ...201728697688
ethambutol partitioning in tuberculous pulmonary lesions explains its clinical efficacy.clinical trials and practice have shown that ethambutol is an important component of the first-line tuberculosis (tb) regime. this contrasts the drug's rather modest potency and lack of activity against nongrowing persister mycobacteria. the standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value. here, we hypothesized that this apparent contradiction may be explained by favorable penetration of the drug into tb lesions. ...201728696241
sterilizing effect of ertapenem-clavulanate in a hollow-fiber model of tuberculosis and implications on clinical dosing.carbapenems are now being explored for treatment of multidrug-resistant tuberculosis (mdr-tb), especially in conjunction with clavulanate. clinical use is constrained by the need for multiple parenteral doses per day and the lack of knowledge of the optimal dose for sterilizing effect. our objective was to identify the ertapenem exposure associated with optimal sterilizing effect and then design a once-a-day dose for clinical use. we utilized the hollow-fiber system model of tuberculosis in a 28 ...201728696238
innate scavenger receptor-a regulates adaptive t helper cell responses to pathogen infection.the pattern recognition receptor (prr) scavenger receptor class a (sr-a) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. however, little is known about the role of sr-a in the host adaptive immune responses to pathogen infection. here we show with mouse models of helminth schistosoma japonicum infection and heat-inactivated mycobacterium tuberculosis stimulation that sr-a is regulated by pathogens and suppresses irf5 ...201728695899
the cording phenotype of mycobacterium tuberculosis induces the formation of extracellular traps in human macrophages.the causative agent of tuberculosis, mycobacterium tuberculosis, shares several characteristics with organisms that produce biofilms during infections. one of these is the ability to form tight bundles also known as cords. however, little is known of the physiological relevance of the cording phenotype. in this study, we investigated whether cord-forming m. tuberculosis induce the formation of macrophage extracellular traps (mets) in human monocyte-derived macrophages. macrophages have previousl ...201728695112
abdominal tuberculosis after removal of an adjustable gastric band - report of an unusual case.laparoscopic adjustable gastric banding (lagb) is the third most popular bariatric procedure. despite its reversibility and minimal invasiveness, band infection affects 1.2% of patients. we present a case of a 25-year-old, obese woman who was experiencing malaise and feverishness 3 years after gastric band placement. due to port site infection the port was removed, which did not improve the patient's condition. after 2 years the band was removed via laparotomy with a minor surgical site infectio ...201728694906
benzoxazoles, phthalazinones, and arylurea-based compounds with impdh-independent antibacterial activity against francisella tularensis.francisella tularensis is the causative agent of tularemia and a potential biowarfare agent. the virulence of f. tularensis is decreased by deletion of guab, the gene encoding inosine monophosphate dehydrogenase (impdh), suggesting that this enzyme is a target for antibacterial design. here we report that f. tularensis growth is blocked by inhibitors of bacterial impdhs. seventeen compounds from two different frameworks, designated d and q, display antibacterial activity with minimum inhibitory ...201728739786
environmental aspects related to tuberculosis and intestinal parasites in a low-income community of the brazilian amazon.we carried out a cross-sectional study from january to december 2015 on 1,425 inhabitants from a floating population in the brazilian amazon (murinin district, pará state) to describe the population-based prevalence of tuberculosis (tb) from 2011 to 2014, recent tb contacts (rcts) latently infected with mycobacterium tuberculosis (ltbi) , the coverage of the local health network, socio-environmental factors, and frequency of intestinal parasitic infection (ipi). we found that the sanitary struct ...201728793025
the arms race between man and mycobacterium tuberculosis: time to regroup.an arms race is an appropriate metaphor to use for the interaction of man and mycobacterium tuberculosis (m.tb) through the millennia. estimates of the time of infection of modern humans with m.tb often pre-date the out-of-africa migration. humans have adapted to the changing environment during the migration with respect to climate, food sources and encounters with local pathogens. more recently, there has been adaptation to the demographic changes brought about in the majority of the human popu ...201728843547
"transition state analogue inhibitors of 5'-deoxyadenosine/5'-methylthioadenosine nucleosidase from mycobacterium tuberculosis".mycobacterium tuberculosis 5'-deoxyadenosine/5'-methylthioadenosine nucleosidase (rv0091) catalyzes the n-riboside hydrolysis of its substrates 5'-methylthioadenosine (mta) and 5-deoxyadenosine (5'-dado). 5'-dado is the preferred substrate, a product of radical sam-dependent enzyme reactions. rv0091 is characterized by a ribocation-like transition state, with low n-ribosidic bond order, an n7 protonated adenine leaving group and an activated but weakly bonded water nucleophile. dadme-immucillin ...201728836767
local genes for local bacteria: evidence of allopatry in the genomes of transatlantic campylobacter populations.the genetic structure of bacterial populations can be related to geographical locations of isolation. in some species, there is a strong correlation between geographical distance and genetic distance, which can be caused by different evolutionary mechanisms. patterns of ancient admixture in helicobacter pylori can be reconstructed in concordance with past human migration, whereas in mycobacterium tuberculosis it is the lack of recombination that causes allopatric clusters. in campylobacter, anal ...201728493321
the conserved actinobacterial two-component system mtrab coordinates chloramphenicol production with sporulation in streptomyces venezuelae nrrl b-65442.streptomyces bacteria make numerous secondary metabolites, including half of all known antibiotics. production of antibiotics is usually coordinated with the onset of sporulation but the cross regulation of these processes is not fully understood. this is important because most streptomyces antibiotics are produced at low levels or not at all under laboratory conditions and this makes large scale production of these compounds very challenging. here, we characterize the highly conserved actinobac ...201728702006
prognostic markers in hiv mono-and co-infected individuals: a study from karachi-pakistan.multiple infections are the most common problem among hiv infected individuals. the prognostic impact of these co infections in hiv-population in resource-limited countries like pakistan has not been fully elucidated. the aim of this study was to assess cd4 and hemoglobin (hb) levels in patients with hiv mono infection and hiv co-infection with hepatitis c (hcv), hepatitis b (hbv) and mycobacterium tuberculosis (mtb).201728844443
the burden and epidemiology of community-acquired central nervous system infections: a multinational study.risk assessment of central nervous system (cns) infection patients is of key importance in predicting likely pathogens. however, data are lacking on the epidemiology globally. we performed a multicenter study to understand the burden of community-acquired cns (ca-cns) infections between 2012 and 2014. a total of 2583 patients with ca-cns infections were included from 37 referral centers in 20 countries. of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) p ...201728397100
epidemiology of drug-resistant tuberculosis in a tertiary care center in oman, 2006-2015.the aim of this study was to estimate the prevalence and identify the risk factors for the development of drug-resistant mycobacterium tuberculosis infection in a tertiary care center in oman.201728042401
performance of xpert mtb/rif on ascitic fluid samples for detection of abdominal tuberculosis.diagnosis of abdominal tuberculosis (tb) from ascitic fluid samples using routinely available diagnostic methods is challenging due to its paucibacillary nature. although performance of xpert mtb/rif assay has been evaluated extensively on pulmonary samples, its performance on extrapulmonary samples is still under evaluation.201728042217
synthesis, identification and in vitro biological evaluation of some novel quinoline incorporated 1,3-thiazinan-4-one derivatives.the present study describes the synthesis of two new series of 3-hydroxy-n-(4-oxo-2-phenyl-1,3-thiazinan-3-yl)-8-(trifluoromethyl)quinoline-2-carboxamide derivatives (4a-j) and 3-((7-chloroquinolin-4-ylamino)methyl)-2-phenyl-1,3-thiazinan-4-one derivatives (5a-7j). all the compounds were synthesized in moderate to good yield by one-pot three component cyclo-condensation reaction. the newly synthesized compounds were characterized by ft-ir, (1)h, (13)c nmr and elemental analysis. the compounds we ...201728065567
disruption of redox catalytic functions of peroxiredoxin-thioredoxin complex in mycobacterium tuberculosis h37rv using small interface binding molecules.mycobacterium tuberculosis has distinctive ability to detoxify various microbicidal superoxides and hydroperoxides via a redox catalytic cycle involving thiol reductants of peroxiredoxin (prx) and thioredoxin (trx) systems which has conferred on it resistance against oxidative killing and survivability within host. we have used computational approach to disrupt catalytic functions of prx-trx complex which can possibly render the pathogen vulnerable to oxidative killing in the host. using protein ...201728063347
dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model.cell biology differs between traditional cell culture and 3-dimensional (3-d) systems, and is modulated by the extracellular matrix. experimentation in 3-d presents challenges, especially with virulent pathogens. mycobacterium tuberculosis (mtb) kills more humans than any other infection and is characterised by a spatially organised immune response and extracellular matrix remodelling. we developed a 3-d system incorporating virulent mycobacteria, primary human blood mononuclear cells and collag ...201728063256
mycobacterium tuberculosis complex exhibits lineage-specific variations affecting protein ductility and epitope recognition.the advent of whole-genome sequencing has provided an unprecedented detail about the evolution and genetic significance of species-specific variations across the whole mycobacterium tuberculosis complex. however, little attention has been focused on understanding the functional roles of these variations in the protein coding sequences. in this work, we compare the coding sequences from 74 sequenced mycobacterial species including m. africanum, m. bovis, m. canettii, m. caprae, m. orygis, and m. ...201728062754
tuberculous scleral abscess with choroidal detachment.we present a case of ocular tuberculosis (tb) presenting as scleral abscess with choroidal detachment. a 60-year-old woman presented with intense pain, redness, watering and decreased vision in the right eye (re) for 1 week duration. slit lamp examination of re revealed diffuse scleritis with two pus-pointing areas in the supero-temporal quadrant suggesting scleral abscess. fundus examination of the re showed choroidal detachment in the temporal and inferior quadrant. left eye examination was un ...201728062426
rna expression analysis of efflux pump genes in clinical isolates of multidrug-resistant and extensively drug-resistant mycobacterium tuberculosis in south korea.tuberculosis (tb), caused by infection with mycobacterium tuberculosis, is an important communicable disease. various mechanisms of resistance to antituberculosis drugs have been reported; these are principally mutations in target genes. however, not all m. tuberculosis resistance can be explained by mutations in such genes. other resistance mechanisms associated with drug transport, such as efflux pumps, have also been reported. in this study, we investigated the expression levels of three puta ...201728062386
new tuberculosis drug leads from naturally occurring compounds.tuberculosis (tb) continues to be a significant cause of mortality and morbidity worldwide. an estimated 2 billion individuals are infected with mycobacterium tuberculosis and annually there are approximately 10 million new cases of clinical tb and 1.5 million deaths. currently available drugs and vaccines have had no significant impact on tb control. in addition, the emergence of drug resistant tb is considered a public health crisis, with some strains now resistant to all available drugs. unfo ...201728062229
hyperthermostable binding molecules on phage: assay components for point-of-care diagnostics for active tuberculosis infection.tuberculosis is the leading cause of death from infectious disease worldwide. the low sensitivity, extended processing time, and high expense of current diagnostics are major challenges to the detection and treatment of tuberculosis. mycobacterium tuberculosis ornithine transcarbamylase (mtb otc, rv1656) has been identified in the urine of patients with active tb infection and is a promising target for point-of-care diagnostics. specific binding proteins with low nanomolar affinities for mtb otc ...201728062210
molecular identification of mycobacterium tuberculosis in cattle.bovine tuberculosis continued to be a re-emerging problem in some countries especially in endemic areas due to the fact that human and animal health surveillance system is not adopted to diagnose the infection. this crisis can be attributed due to sharing of the same habitat especially in rural areas. in the present study, a total of 148 samples were collected from cattle for isolation over a period of 3 years from cattle with and without lesions, of which 67 isolates were obtained by culture. f ...201728062011
multiple cytokine responses in discriminating between active tuberculosis and latent tuberculosis infection.cytokines play an important role in cell-mediated immune responses against mycobacterium tuberculosis (mtb) infection. cytokine profile specifically associated with active tuberculosis (atb) patients, subjects with latent tuberculosis infection (ltbi) and non-infected individuals remains to be determined.201728061954
advances in basic and translational tuberculosis research: proceedings of the first meeting of report international.report international is a collaborative research network of investigators from multiple countries and institutions with the goal of establishing a bio-repository of specimens and clinical data for the study of active tb and latent tb infection (ltbi). during the first meeting of report international in boston, massachusetts, the results of research pertinent to tb control and eradication were presented, including advances in the research of mycobacterium tuberculosis (mtb) persistence and drug r ...201728061953
role and contribution of pulmonary cd103(+) dendritic cells in the adaptive immune response to mycobacterium tuberculosis.despite international control programmes, the global burden of tuberculosis remains enormous. efforts to discover novel drugs have largely focused on targeting the bacterium directly. alternatively, manipulating the host immune response may represent a valuable approach to enhance immunological clearance of the bacilli, but necessitates a deeper understanding of the immune mechanisms associated with protection against mycobacterium tuberculosis infection. here, we examined the various dendritic ...201728061951
levels of microrna mir-16 and mir-155 are altered in serum of patients with tuberculosis and associate with responses to therapy.identification of blood biomarkers that can be useful for predicting mycobacterium tuberculosis (m.tb) infection, effect of therapy and multi drug resistant (mdr) tb infected individuals is clinically useful for combating tuberculosis epidemic. in this study, we have evaluated the levels of selected mirnas in serum of tb and mdr tb patients. in addition, we have studied their levels in serum of patients post-therapy. the levels of 4-mirnas (mir-16, mir-29a, mir-125b and mir-155) were measured in ...201728061948
diagnostic yield of nontuberculous mycobacteria in patients booked for endoscopy at the university teaching hospital, lusaka.the intestinal carriage of nontuberculous mycobacteria (ntm) is associated with disease, especially in severely immunocompromised individuals. these organisms, although often considered contaminants, have been known to cause various types of illnesses. we aimed to determine the prevalence of and associated factors for ntm among patients booked for colonoscopy at the university teaching hospital (uth) in lusaka.201728061885
il-37 confers protection against mycobacterial infection involving suppressing inflammation and modulating t cell activation.interleukin-37 (il-37), a novel member of the il-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (tb) has not been clearly elucidated. in this study, single nucleotide polymorphism (snp) analysis demonstrated an association of the genetic variant rs3811047 of il-37 with tb susceptibility. in line with previous report, a significant elevated il-37 abundance in the ...201728076390
biosynthesis of the methylthioxylose capping motif of lipoarabinomannan in mycobacterium tuberculosis.lipoarabinomannan (lam) is a lipoglycan found in abundant quantities in the cell envelope of all mycobacteria. the nonreducing arabinan termini of lam display species-specific structural microheterogeneity that impacts the biological activity of the entire molecule. mycobacterium tuberculosis, for instance, produces mannoside caps made of one to three α-(1 → 2)-manp-linked residues that may be further substituted with an α-(1 → 4)-linked methylthio-d-xylose (mtx) residue. while the biological fu ...201728075556
discovery of imidazo[1,2-a]pyridine ethers and squaramides as selective and potent inhibitors of mycobacterial adenosine triphosphate (atp) synthesis.the approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (atp) synthase as an attractive target to kill mycobacterium tuberculosis (mtb). herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (ipe) and squaramides (sqa) as inhibitors of mycobacterial atp synthesis. through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an atp synth ...201728075132
binding and processing of β-lactam antibiotics by the transpeptidase ldtmt2 from mycobacterium tuberculosis.β-lactam antibiotics represent a novel direction in the chemotherapy of tuberculosis that brings the peptidoglycan layer of the complex mycobacterial cell wall in focus as a therapeutic target. peptidoglycan stability in mycobacterium tuberculosis, especially during infection, relies on the nonconventional peptide cross-links formed by l,d-transpeptidases. these enzymes are known to be inhibited by β-lactams, primarily carbapenems, leading to a stable covalent modification at the enzyme active s ...201728075068
dynamics of fluoroquinolones induced resistance in dna gyrase of mycobacterium tuberculosis.dna gyrase is a validated target of fluoroquinolones which are key components of multidrug resistance tuberculosis (tb) treatment. most frequent occurring mutations associated with high level of resistance to fluoroquinolone in clinical isolates of tb patients are a90v, d94g, and a90v-d94g (double mutant [dm]), present in the larger subunit of dna gyrase. in order to explicate the molecular mechanism of drug resistance corresponding to these mutations, molecular dynamics (md) and mechanics appro ...201728071975
the ppe2 protein of mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production.mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. it has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. here, we show that one of the unique ppe family member proteins of m. tuberculosis, ppe2, can limit nitric oxide (no) production by inhibiting inos gene transcription. ppe2 protein has a leucine zipper dna-binding motif and a functional n ...201728071726
whole-genome sequences of mycobacterium tuberculosis tb282 and tb284, a widespread and a unique strain, respectively, identified in a previous study of tuberculosis transmission in central los angeles, california, usa.we report here the genome sequences of two mycobacterium tuberculosis clinical isolates previously identified in central los angeles, ca, in the 1990s using a pacbio platform. isolate tb282 represents a large-cluster strain that caused 27% of the tuberculosis cases, while tb284 represents a strain that caused disease in only one patient.201728082486
oligomeric state of hypoxanthine-guanine phosphoribosyltransferase from mycobacterium tuberculosis.sedimentation equilibrium and size-exclusion chromatography experiments on mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase (mthgprt) have established the existence of this enzyme as a reversibly associating mixture of dimeric and tetrameric species in 0.1 m tris-hcl-0.012 m mgcl2, ph 7.4. displacement of the equilibrium position towards the larger oligomer by phosphate signifies the probable existence of mthgprt as a tetramer in the biological environment. these data th ...201728082125
the bare essentials of antibiotic target validation.the convergence of competitive fitness experiments and phenotypic screening would seem to be an auspicious beginning for validation of an antibacterial target. impdh was already identified an essential protein in mycobacterium tuberculosis when not one, but two, groups discovered inhibitors with promising antitubercular activity. a new target appeared to be born. surprisingly, the two groups came to completely different conclusions about the vulnerability of impdh and its future as a drug target ...201728081610
structure-activity relationships of spectinamide antituberculosis agents: a dissection of ribosomal inhibition and native efflux avoidance contributions.spectinamides are a novel class of antitubercular agents with the potential to treat drug-resistant tuberculosis infections. their antitubercular activity is derived from both ribosomal affinity and their ability to overcome intrinsic efflux mediated by the mycobacterium tuberculosis rv1258c efflux pump. this study explores the structure-activity relationships through analysis of 50 targeted spectinamides. compounds are evaluated for ribosomal translational inhibition, mic activity in rv1258c ef ...201728081607
diagnostic accuracy of genexpert mtb/rif assay in comparison to conventional drug susceptibility testing method for the diagnosis of multidrug-resistant tuberculosis.xpert mtb/rif assay is regarded as a great achievement of modern medicine for the rapid diagnosis of multidrug-resistant tuberculosis (mdr-tb). the main purpose of this study was to determine the performance of xpert mtb/rif assay compared to conventional drug susceptibility testing (dst) method for the diagnosis of mdr-tb. a comparative cross sectional study was carried out at german-nepal tuberculosis project, kathmandu, nepal, from april 2014 to september 2014. a total of 88 culture positive ...201728081227
assessment of a 96-well plate assay of quantitative drug susceptibility testing for mycobacterium tuberculosis complex in china.to evaluate the performance of the sensitire mycotb mic plate (mycotb) which could measure the twelve anti-tuberculosis drugs susceptibility on one 96-wells plate.201728081169
isoniazid: a review of characteristics, properties and analytical methods.isoniazid is a synthetic antimicrobial and one of the most important first-line drugs used in the treatment of tuberculosis. since it was introduced in the therapy in 1952, the drug remains at the front line of the antituberculosis treatment mainly due to its potency and high selectivity against mycobacterium tuberculosis. pharmaceutical analysis and therapeutic drug monitoring of isoniazid in both, pharmaceuticals and biological samples, plays an important role to comprehend aspects regarding t ...201728080136
the quantiferon-tb gold in-tube assay in neuro-ophthalmology.although quantiferon-tb gold in-tube (qft-git) testing is regularly used to detect infection with mycobacterium tuberculosis, its utility in a patient population with a low risk for tuberculosis (tb) has been questioned. the following is a cohort study analyzing the efficacy of qft-git testing as a method for detection of active tb disease in low-risk individuals in a neuro-ophthalmologic setting.201728079759
corrigendum: construction and application of a co-expression network in mycobacterium tuberculosis. 201728079164
synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents.resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a-5c) have been synthesized and screened for their antitubercular activity against mycobacterium tuberculosis h37ra (h37ra). the triazolethiones 4b and 4v showed high antitubercular activity (both mic and ic50 ) against the dormant h37ra by in vitro and ex vivo. they were ...201728083914
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