Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
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
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
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
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
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
working conditions and tuberculosis mortality in england and wales, 1890-1912: a retrospective analysis of routinely collected data.modelling studies suggest that workplaces may be important sites of mycobacterium tuberculosis transmission in high burden countries today. contemporary data on tuberculosis by occupation from these settings are scarce. however, historical data on tuberculosis risk in different occupations are available and may provide insight into workplace transmission. we aimed to ascertain whether, in a high burden setting, individuals working in crowded indoor environments (exposed) had greater tuberculosis ...201627207086
design, synthesis and biological evaluation of novel quinoline-based carboxylic hydrazides as anti-tubercular agents.in this study, seventeen novel quinoline-based carboxylic hydrazides were designed as potential anti-tubercular agents using molecular hybridization approach and evaluated in-silico for drug-likeness behavior. the compounds were synthesized, purified, and characterized using spectral techniques (like ftir, (1) h nmr, and mass). the in-vitro anti-tubercular activity (against mycobacterium tuberculosish37ra) and cytotoxicity against human lung fibroblast cells were studied. among the tested hydraz ...201627203404
role of alanine dehydrogenase of mycobacterium tuberculosis during recovery from hypoxic nonreplicating persistence.mycobacterium tuberculosis can maintain a nonreplicating persistent state in the host for decades, but must maintain the ability to efficiently reactivate and produce active disease to survive and spread in a population. among the enzymes expressed during this dormancy is alanine dehydrogenase, which converts pyruvate to alanine, and glyoxylate to glycine concurrent with the oxidation of nadh to nad. it is involved in the metabolic remodeling of m. tuberculosis through its possible interactions ...201627203084
modular organization of the esx-5 secretion system in mycobacterium tuberculosis.mycobacteria utilize type vii secretion systems (t7ss) to export many of their important virulence proteins. the t7ss encompasses five homologous secretion systems (esx-1 to esx-5). most pathogenic mycobacterial species, including the human pathogen mycobacterium tuberculosis, possess all five esx systems. the esx-1, -3, and -5 systems are important for virulence of mycobacteria but the molecular mechanisms of their secretion apparatus and the identity and activity of secreted effector proteins ...201627200304
multi-fluorescence real-time pcr assay for detection of rif and inh resistance of m. tuberculosis.failure to early detect multidrug-resistant tuberculosis (mdr-tb) results in treatment failure and poor clinical outcomes, and highlights the need to rapidly detect resistance to rifampicin (rif) and isoniazid (inh).201627199947
scenario analysis for programmatic tuberculosis control in western province, papua new guinea.tuberculosis (tb) and multidrug-resistant tb (mdr-tb) are major health problems in western province, papua new guinea. while comprehensive expansion of tb control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. we parameterized our previously described mathematical model of mycobacterium tuberculosis dynamics in western province, following an epidemiologic assessment. five hypothetical scenarios representing a ...201627199387
complete genome sequence of mycobacterium tuberculosis clinical isolate spoligotype sit745/eai1-mys.mycobacterium tuberculosis is known to cause pulmonary and extrapulmonary tuberculosis. this organism showed special phylogeographical specificity. here, we report the complete genome sequence of m. tuberculosis clinical isolate spoligotype sit745/eai1-mys, which was isolated from a malaysian tuberculosis patient.201627198011
functional characterization of pyrg, an unusual nonribosomal peptide synthetase module from the pyridomycin biosynthetic pathway.pyridomycin is an antimycobacterial cyclodepsipeptide assembled by a nonribosomal peptide synthetase/polyketide synthase hybrid system. analysis of its cluster revealed a nonribosomal peptide synthetase (nrps) module, pyrg, that contains two tandem adenylation domains and a pks-type ketoreductase domain. in this study, we biochemically validated that the second a domain recognizes and activates α-keto-β-methylvaleric acid (2-kvc) as the native substrate; the first a domain was not functional but ...201627197800
capillary electrophoresis as a method to determine underivatized urinary lipoarabinomannans, a biomarker of active tuberculosis caused by mycobacterium tuberculosis.tuberculosis is a devastating contagious disease caused by mycobacterium tuberculosis. this is the first report describing the development of novel capillary electrophoresis methods to detect lipoarabinomannans shed into the blood circulation by replicating bacteria. the novelty of the methods is the detection without derivatization. the lipoarabinomannan is detected owing to the ionization of the diverse functional groups of the structure, such as the multibranched mannan domain or the phosphat ...201627196985
in vitro activity of copper(ii) complexes, loaded or unloaded into a nanostructured lipid system, against mycobacterium tuberculosis.tuberculosis (tb) is an infectious disease caused mainly by the bacillus mycobacterium tuberculosis (mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. the aim of this study was to evaluate a nanostructured lipid system (nls) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and eumulgin(®) hre 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer ph = 7.4) as a tactic to ...201627196901
[preclinical and clinical trials of the new tuberculosis drug perchlozon].the paper sets forth the stages of design and introduction of the new russian tuberculosis (tb) drug perchlozon registered in the russian federation in 2012. based on the results of phases i-iii clinical trials, the authors evaluate the efficacy and safety of the agent and consider the adverse effects of its treatment for respiratory tb. the use of perchlozon as a component of combination therapy versus standard chemotherapy regimens significantly reduces abacillation time in pulmonary tb caused ...201627195324
evaluation of the effect of pulicaria gnaphalodes and perovskia abrotanoides essential oil extracts against mycobacterium tuberculosis strains.mycobacterium tuberculosis (mtb) is the causative agent of tuberculosis (tb), which remains one of the major public health problems in the world. the increasing incidence of multidrug-resistant tuberculosis (mdr-tb) and extensively drug-resistant tuberculosis (xdr-tb) worldwide highlights the urgent need to search for alternative antimycobacterial agents. more and more people in developing countries utilize traditional medicine for their major primary health care needs. it has been determined th ...201627195252
interleukin-10 family and tuberculosis: an old story renewed.the interleukin-10 (il-10) family of cytokines consists of six immune mediators, namely il-10, il-19, il-20, il-22, il-24 and il-26. il-10, il-22, il-24 and il-26 are critical for the regulation of host defense against mycobacterium tuberculosis infections. specifically, il-10 and il-26 can suppress the antimycobacterial immunity and promote the survival of pathogen, while il-22 and il-24 can generate protective responses and inhibit the intracellular growth of pathogen. knowledge about the new ...201627194948
the emergence of latent infection in the early evolution of mycobacterium tuberculosis.mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. from the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a détente with the host immune response. however, a small fraction of latent infections reactivate to the disease state. thus, latency has been argued to provide a safe harbour for future infections ...201627194699
standard genotyping overestimates transmission of mycobacterium tuberculosis among immigrants in a low-incidence country.immigrants from regions with a high incidence of tuberculosis (tb) are a risk group for tb in low-incidence countries such as switzerland. in a previous analysis of a nationwide collection of 520 mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat [miru-vntr] typing and spoligotyping). here, we used whole-genome sequencing (wgs) to re ...201627194683
triclosan-induced genes rv1686c-rv1687c and rv3161c are not involved in triclosan resistance in mycobacterium tuberculosis.a key issue towards developing new chemotherapeutic approaches to fight mycobacterium tuberculosis is to understand the mechanisms underlying drug resistance. previous studies have shown that genes rv1686c-rv1687c and rv3161c, predicted to encode an atp-binding cassette transporter and a dioxygenase respectively, are induced in the presence of triclosan and other antimicrobial compounds. therefore a possible role in drug resistance has been suggested for the products of these genes although no f ...201627193696
anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of melophlus sp.tuberculosis (tb), caused by mycobacterium tuberculosis infection, is a major world health problem that is responsible for the deaths of 1.5 million people each year. in addition, the requirement for long-term therapy to cure tb complicates treatment of the disease. one of the major reasons for the extended chemotherapeutic regimens and wide epidemicity of tb is that m. tuberculosis has the ability to persist in a dormant state. we therefore established a new screening system to search for subst ...201627193014
molecular characterization of mycobacterium tuberculosis isolates from tehran, iran by restriction fragment length polymorphism analysis and spoligotyping.introduction characterization of mycobacterium tuberculosis (mtb) isolates by dna fingerprinting has contributed to tuberculosis (tb) control. the aim of this study was to determine the genetic diversity of mtb isolates from tehran province in iran. methods mtb isolates from 60 iranian and 10 afghan tb patients were fingerprinted by standard is6110-restriction fragment length polymorphism (rflp) analysis and spoligotyping. results the copy number of is6110 ranged from 10-24 per isolate. the isol ...201627192590
total synthesis of teixobactin.the first total synthesis of the cyclic depsipeptide natural product teixobactin is described. synthesis was achieved by solid-phase peptide synthesis, incorporating the unusual l-allo-enduracididine as a suitably protected synthetic cassette and employing a key on-resin esterification and solution-phase macrolactamization. the synthetic natural product was shown to possess potent antibacterial activity against a range of gram-positive pathogenic bacteria, including a virulent strain of mycobact ...201627191730
3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamides bearing hydrophobic substituents at the 7-position of the benzodioxane nucleus potently inhibit methicillin-resistant sa and mtb cell division.lipophilic substituents at benzodioxane c (7) of 3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamide improve the antibacterial activity against methicillin-resistant staphylococcus aureus strains to mic values in the range of 0.2-2.5 μg/ml, whereas hydrophilic substituents at the same position and modifications at the benzodioxane substructure, excepting for replacement with 2-cromanyl, are deleterious. some of the lead compounds also exhibit good activity against mtb. parallel sars to those of 3- ...201627191617
next-generation sequencing of mycobacterium tuberculosis. 201627191040
structure-based epitope mapping of mycobacterium tuberculosis secretary antigen mtc28.secretary proteins of mycobacterium tuberculosis are key players of the mycobacterial infection pathway. mtc28 is a 28-kda proline-rich secretary antigen of mycobacterium tuberculosis and is only conserved in pathogenic strains of mycobacteria. here we report the crystal structure of mtc28 at 2.8- and 2.15-å resolutions for the structure-based epitope design. mtc28 shares a "mog1p"-fold consisting of seven antiparallel β strands stacked between α helices. five probable epitopes have been located ...201627189947
bacillus calmette-guérin-inoculation at different time points influences the outcome of c57bl/6 mice infected with plasmodium chabaudi chabaudi as.bacillus calmette-guérin (bcg) is an attenuated mycobacterium tuberculosis vaccine. we performed a series of co-infection experiments with bcg-plasmodium chabaudi chabaudi landau, 1965 as using c57bl/6 mice to analyse whether bcg can affect the development of protective immunity to infection with plasmodium spp. and the mechanism of this protection. we divided mice into four groups: bcg-inoculation 4 weeks prior to p. c. chabaudi as infection (b-4w-pc); simultaneous bcg-inoculation and p. c. cha ...201627188912
mutations in pepq confer low-level resistance to bedaquiline and clofazimine in mycobacterium tuberculosis.the novel atp synthase inhibitor bedaquiline recently received accelerated approval for treatment of multidrug-resistant tuberculosis and is currently being studied as a component of novel treatment-shortening regimens for drug-susceptible and multidrug-resistant tuberculosis. in a limited number of bedaquiline-treated patients reported to date, ≥4-fold upward shifts in bedaquiline mic during treatment have been attributed to non-target-based mutations in rv0678 that putatively increase bedaquil ...201627185800
[eales' disease].the syndrome of recurrent vitreous hemorrhages in young men was described for the first time by henry eales in 1880. the association with a clinical manifestation of ocular inflammation was reported 5years later. eales disease affects young adults who present with ischemic retinal vasculitis, with the peripheral retina most commonly affected. most cases have been reported in south asia. although the etiology of this abnormality is unknown, it may be related to an immune sensitivity to mycobacter ...201627185661
synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine-3-carboxamides.a series of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine carboxamides 7a-s were designed and synthesized. the required building block, 2-dibenzo[b,d]thiophenyl imidazo[1,2-a]pyridine carboxylic acid (5) was synthesized from commercial dibenzo[b,d]thiophene in good yields following five-step reaction sequence. the desired carboxamides 7a-s was prepared through coupling of acid 5 with various benzyl amines. all the new analogues 7a-s was characterized by their nmr and mass spectral ...201627184765
the effect of growth rate on pyrazinamide activity in mycobacterium tuberculosis - insights for early bactericidal activity?pyrazinamide (pza) plays an essential part in the shortened six-month tuberculosis (tb) treatment course due to its activity against slow-growing and non-replicating organisms. we tested whether pza preferentially targets slow growing cells of mycobacterium tuberculosis that could be representative of bacteria that remain after the initial kill with isoniazid (inh), by observing the response of either slow growing or fast growing bacilli to differing concentrations of pza.201627184366
[molecular characteristics of the multidrug-resistant mycobacterium tuberculosis strains in the northwest russia].the goal of this work was to study the genotypic characteristics of the multidrug-resistant (mdr, i.e., resistant to at least rifampicine and isoniazid) mycobacterium tuberculosis strains isolated in 2011-2012 from tuberculosis (tb) patients in the northwest russia. spoligotyping of 195 m. tuberculosis isolates identified 14 different spoligotypes and assigned isolates to the genetic families beijing (n = 162, 83%), lam (n = 15), h3/ural (n = 14), as well as t, haarlem and x. spoligotypes sit1 ( ...201627183719
heme oxygenase-1 regulates inflammation and mycobacterial survival in human macrophages during mycobacterium tuberculosis infection.mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. we previously showed that m. tuberculosis infection in mice induces expression of the co-producing enzyme heme oxygenase (ho1) and that co is sensed by m. tuberculosis to initiate a dormancy program. further, mice deficient in ho1 succumb to m. tuberculosis infection more readily than do wild-type mice. although mouse macrophages control intracellular m. tuberculosis infection through ...201627183573
maintenance of mycobacterium tuberculosis-specific t cell responses in end stage renal disease (esrd) and implications for diagnostic efficacy.end-stage renal disease (esrd) patients exhibit elevated risk of tuberculosis (tb) reactivation, but current diagnostics, including the interferon gamma release assay (igra), exhibit poor sensitivity in esrd. we tested 80 esrd patients and found an 18.75% prevalence of igra positivity. a subset of patients was assessed for mtb-specific expression of 44 cytokines/chemokines, and cd4+ t cell phenotype and function. similar to non-esrd igra+ individuals, mtb-specific ifnγ, il-1ra, ip-10, mcp-3 and ...201627181992
targeting multiple response regulators of mycobacterium tuberculosis augments the host immune response to infection.the genome of m. tuberculosis (mtb) encodes eleven paired two component systems (tcss) consisting of a sensor kinase (sk) and a response regulator (rr). the sks sense environmental signals triggering rr-dependent gene expression pathways that enable the bacterium to adapt in the host milieu. we demonstrate that a conserved motif present in the c-terminal domain regulates the dna binding functions of the ompr family of mtb rrs. molecular docking studies against this motif helped to identify two m ...201627181265
reynosin and santamarine: two sesquiterpene lactones from ambrosia confertiflora with bactericidal activity against clinical strains of mycobacterium tuberculosis.tuberculosis is primarily caused by mycobacterium tuberculosis (mtb). previous studies have shown that the dichloromethanic extract of ambrosia confertiflora dc (asteraceae) inhibited mtb.201627180996
[analysis on the polymorphisms of human b cell epitopes of 5 specificity antigens in mycobacterium tuberculosis in china].to study the diversities of human b cell epitopes of five proteins (mpt83, mpt70, lpqh, psts3, groes) in mycobacterium tuberculosis isolates from china.201627180592
profiling esterases in mycobacterium tuberculosis using far-red fluorogenic substrates.enzyme-activated, fluorogenic probes are powerful tools for studying bacterial pathogens, including mycobacterium tuberculosis (mtb). in prior work, we reported two 7-hydroxy-9h-(1,3-dichloro-9,9-dimethylacridin-2-one) (ddao)-derived acetoxymethyl ether probes for esterase and lipase detection. here, we report four-carbon (c4) and eight-carbon (c8) acyloxymethyl ether derivatives, which are longer-chain fluorogenic substrates. these new probes demonstrate greater stability and lipase reactivity ...201627177211
high persister mutants in mycobacterium tuberculosis.mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. while genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. the mechanism of persister formation in m. tuberculosis is not well understood. in this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. in ...201627176494
Refresh
firstprev
...11121314151617181920...
nextlast
Displaying items 1801 - 1900 of 53400