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new mycobacterium tuberculosis beijing clonal complexes in china revealed by phylogenetic and bayesian population structure analyses of 24-loci miru-vntrs.beijing lineage of mycobacterium tuberculosis constitutes the most predominant lineage in east asia. beijing epidemiology, evolutionary history, genetics are studied in details for years revealing probable origin from china followed by worldwide expansion, partially linked to higher mutation rate, hypervirulence, drug-resistance, and association with cases of mixed infections. considering huge amount of data available for 24-loci mycobacterial interspersed repetitive units-variable number of tan ...201728729708
high proportion of modern genotypes of m. tuberculosis and their affinity with drug resistance in northern region of india.comparative genomics on the basis of tbd1 deletion has differentiated the members of mycobacterium tuberculosis complex (mtc) in two major genogroups. they exhibit differential distribution and virulence potential. the present study was carried out to see the proportion of these genogroups and their association with drug resistance.201728729202
[changes and differences of dna methylation in human macrophages infected with virulent and avirulent mycobacterium tuberculosis].objective: to profile dna methylation and compare differentially methylated region (dmr) of macrophages infected with virulent and avirulent strains of mycobacterium tuberculosis (mtb). methods: pma(50 ng/ml) treated thp-1 macrophages were left uninfected or infected with the virulent h37rv(thp-1/rv) or avirulent h37ra(thp-1/ra). the genomic dna was then extracted and dna methylation was profiled via reduced representation bisulfite sequencing (rrbs). the dna methylation pattern and dmrs between ...201728728275
performance of clinical prediction rules for diagnosis of pleural tuberculosis in a high-incidence setting.diagnosis of pleural tuberculosis (pt) is still a challenge, particularly in resource-constrained settings. alternative diagnostic tools are needed. we aimed at evaluating the utility of clinical prediction rules (cprs) for diagnosis of pleural tuberculosis in peru.201728727272
cyclic di-gmp regulates mycobacterium tuberculosis resistance to ethionamide.tuberculosis is still on the top of infectious diseases list on both mobility and mortality, especially due to drug-resistance of mycobacterium tuberculosis (m.tb). ethionamide (eth) is one of effective second line anti-tb drugs, a synthetic compound similar to isoniazid (inh) structurally, with existing severe problem of eth resistance. eth is a prodrug, which is activated by etha inside m.tb, and etha is transcriptionally repressed by ethr. we found that c-di-gmp could bind ethr, enhanced the ...201728725053
novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children.pediatric tuberculosis (tb) is challenging to diagnose, confirmed by growth of mycobacterium tuberculosis at best in 40% of cases. the who has assigned high priority to the development of non-sputum diagnostic tools. we therefore sought to identify transcriptional signatures in whole blood of indian children, capable of discriminating intra-thoracic tb disease from other symptomatic illnesses. we investigated the expression of 198 genes in a training set, comprising 47 tb cases (19 definite/28 p ...201728724962
co-expression network analysis of toxin-antitoxin loci in mycobacterium tuberculosis reveals key modulators of cellular stress.research on toxin-antitoxin loci (ta loci) is gaining impetus due to their ubiquitous presence in bacterial genomes and their observed roles in stress survival, persistence and drug tolerance. the present study investigates the expression profile of all the seventy-nine ta loci found in mycobacterium tuberculosis. the bacterium was subjected to multiple stress conditions to identify key players of cellular stress response and elucidate a ta-coexpression network. this study provides direct experi ...201728724903
matrixlysis, an improved sample preparation method for recovery of mycobacteria from animal tissue material.mycobacterium caprae, a member of the mycobacterium tuberculosis complex, is the main causative agent of bovine tuberculosis in alpine regions. bacterial culture is the gold standard in bovine tuberculosis diagnostic but takes up to twelve weeks. this increases the time and costs for stocks affected with bovine tuberculosis. hence this study focused on the implementation of a fast and precise mycobacterial detection method and compared it with currently used methods. matrix lysis is a chemical l ...201728723969
asymptomatic congenital tuberculosis: a case report.congenital tuberculosis (tb) is described as a rare, but severe disease. in contrast to the cases with severe symptoms reported so far, we describe a child with asymptomatic congenital tb.201728723785
molecular characterization of mycobacterium tuberculosis strains with tb-sprint.we evaluated tuberculosis-spoligo-rifampicin-isoniazid typing (tb-sprint), a microbead-based method for spoligotyping and detection of rifampicin and isoniazid resistance in mycobacterium tuberculosis. for that, 67 m. tuberculosis complex strains were retrospectively selected. membrane-based spoligotyping, restriction fragment length polymorphism, dna sequencing/pyrosequencing of rpob, katg, and inha promoter, tb-sprint, and snp typing were performed. concordance between spoligotyping methods wa ...201728722603
mycobacterium tuberculosis infection in close childhood contacts of adults with pulmonary tuberculosis is increased by secondhand exposure to tobacco.tobacco use is a major risk factor for tuberculosis (tb). secondhand smoke (shs) is also a risk factor for tb and to a lesser extent, mycobacterium tuberculosis infection without disease. we investigated the added risk of m. tuberculosis infection due to shs exposure in childhood contacts of tb cases in the gambia. participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary tb (ptb) cases. the intensity of exposure to the case was categorized according to whether ...201728722570
contribution of brain ct in the diagnosis of tuberculous meningitis: a case report from djibouti.tuberculous meningitis, a serious disease with high mortality and morbidity, remains frequent in countries with endemic tuberculosis. its non-specific presentation often delays the introduction of appropriate treatment. its definitive diagnosis requires isolation of mycobacterium tuberculosis from cerebrospinal fluid, although this test may be negative without conclusively ruling out this diagnosis. a presumptive diagnosis should be reached as soon as possible through a body of clinical evidence ...201728721934
mapping and characterization of g-quadruplexes in mycobacterium tuberculosis gene promoter regions.mycobacterium tuberculosis is the causative agent of tuberculosis (tb), one of the top 10 causes of death worldwide in 2015. the recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. g-quadruplexes are nucleic acids secondary structures that may form in g-rich regions to epigenetically regulate cellular functions. here we implemented a computational tool to scan the presence of putative g-quadruplex forming sequences in the g ...201728720801
predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells.tuberculosis (tb) is a deadly infectious disease, which kills millions of people every year. the causative pathogen, mycobacterium tuberculosis (mtb), is estimated to have infected up to a third of the world's population; however, only approximately 10% of infected healthy individuals progress to active tb. despite evidence for heritability, it is not currently possible to predict who may develop tb. to explore approaches to classify susceptibility to tb, we infected with mtb dendritic cells (dc ...201728720766
serologic responses in childhood pulmonary tuberculosis.identification of the mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (tb). we investigated igg antibody responses against m. tuberculosis antigens in children with well-characterized tb.201728719497
case report: disseminated talaromyces (penicillium) marneffei and mycobacterium tuberculosis coinfection in a japanese patient with acquired immunodeficiency syndrome.talaromyces marneffei is a dimorphic fungus endemic mainly in southeast and south asia. it causes severe mycosis, usually in immunocompromised individuals, such as those with human immunodeficiency virus (hiv) infection. concomitant infection with t. marneffei and other opportunistic pathogens is plausible because the majority of t. marneffei infections occur in patients with advanced hiv infection. nonetheless, coinfection in the same site has rarely been reported, and poses a considerable diag ...201728719322
regional differences in the prevalence of major opportunistic infections among antiretroviral-naïve human immunodeficiency virus patients in japan, northern thailand, northern vietnam, and the philippines.to identify regional differences in the distribution of opportunistic infections (ois) among human immunodeficiency virus (hiv)-infected patients in asia, the medical records of antiretroviral therapy (art)-naïve patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: nagoya medical center (nmc, nagoya, japan), lampang hospital (lph, lampang, northern thailand), bach mai hospital (bmh, hanoi, northern vietnam), and philippine general hospital (pgh, manila, philipp ...201728719295
the human microbiome in the fight against tuberculosis.abstractthe human microbiome is an intriguing potentially modifiable risk factor in our arsenal against mycobacterium tuberculosis, the leading infectious disease killer globally. previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (tb) infection or disease remain unclear. immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against tb, incl ...201728719264
deletion of sigb causes increased sensitivity to para-aminosalicylic acid and sulfamethoxazole in mycobacterium tuberculosis.although the de novo folate biosynthesis pathway has been well studied in bacteria, little is known about its regulation. in this study, the sigb gene in mycobacterium tuberculosis (m. tb) was deleted. subsequent drug susceptibility tests revealed that m. tb δsigb was more sensitive to para-aminosalicylic acid (pas) and sulfamethoxazole (smx). comparative transcriptional analysis was performed and down-regulation of pabb was observed in the sigb deleted strain, which was further verified by qrt- ...201728717039
incidence of active tuberculosis in individuals with latent tuberculosis infection in rural china: follow-up results of a population-based, multicentre, prospective cohort study.the management of latent mycobacterium tuberculosis infection is a new priority action for the who end tuberculosis (tb) strategy. however, national guidelines on latent tuberculosis infection testing and treatment have not yet been developed in china. here, we present the results from the 2-year follow-up of a study that aimed to track the development of active disease in individuals with latent tuberculosis infection, identify priority populations for latent infection management, and explore t ...201728716677
a comparative study of phenotypic and genotypic first- and second-line drug resistance testing of mycobacterium tuberculosis.this study aimed to evaluate the frequency of resistance to first- and second-line drugs using phenotypic and genotypic methods and its correlation with resistance-linked mutations in mycobacterium tuberculosis (m. tb) isolated in iran. three different methods, including the indirect proportion method(pm), direct and indirect nitrate reductase assay(nra), and direct sequencing were used to assess drug resistance. in this study, sensitivity, specificity, agreement, costs, and turnaround time of t ...201728716625
rapid identification of a mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum.resistance to second-line tuberculosis drugs is common, but slow to diagnose with phenotypic drug sensitivity testing. rapid molecular tests speed up diagnosis, but can only detect limited mutations. whole genome sequencing (wgs) of culture isolates can generate a complete genetic drug resistance profile, but is delayed by the initial culture step. in the case presented here, successful wgs directly from sputum was achieved using targeted enrichment.201728716462
the role of efflux pumps in tuberculosis treatment and their promise as a target in drug development: unraveling the black box.insight into drug transport mechanisms is highly relevant to the efficacious treatment of tuberculosis (tb). major problems in tb treatment are related to the transport of antituberculosis (anti-tb) drugs across human and mycobacterial membranes, affecting the concentrations of these drugs systemically and locally. firstly, transporters located in the intestines, liver, and kidneys all determine the pharmacokinetics and pharmacodynamics of anti-tb drugs, with a high risk of drug-drug interaction ...201728715978
new findings of toll-like receptors involved in mycobacterium tuberculosis infection.tuberculosis (tb), an important issue in the present age, affects millions of people each year. the infectious agent of tb, mycobacterium tuberculosis (mtb), interacts with the immune system which prevents the development of this bacterium as much as possible. in fact, the receptors on the surface of immune cells identify the bacteria, one of which is toll-like receptors (tlrs). different tlrs including 2, 4, 9 and 8 play critical roles in tuberculosis infection. in this paper, we focused on the ...201728715935
design, synthesis and 2d qsar study of novel pyridine and quinolone hydrazone derivatives as potential antimicrobial and antitubercular agents.the increased development of highly resistant bacterial strains and tuberculosis, constitute a serious public health threat, highlighting the urgent need of novel antibacterial agents. in this work, two novel series of nicotinic acid hydrazone derivatives (6a-r) and quinolone hydrazide derivatives (12a-l) were synthesized and evaluated as antimicrobial and antitubercular agents. the synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antimycobacterial activities ...201728715707
antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes.isonicotinyl and pyrazinyl ferrocenyl-derived complexes were prepared using various hydrazides and ferrocenyl aldehydes. three heterobimetallic complexes were also synthesized from the schiff base-derived isonicotinyl ferrocene complex using various platinum group metal dimers based on ruthenium, rhodium and iridium. all complexes were evaluated in vitro for antimycobacterial and antiparasitic activity. against mycobacterium tuberculosis h37rv, the platinum group metal complexes showed glycerol- ...201728713884
role of interferons in the development of diagnostics, vaccines, and therapy for tuberculosis.tuberculosis (tb) is an airborne infection caused by mycobacterium tuberculosis (mtb). about one-third of the world's population is latently infected with tb and 5-15% of them will develop active tb in their lifetime. it is estimated that each case of active tb may cause 10-20 new infections. host immune response to mtb is influenced by interferon- (ifn-) signaling pathways, particularly by type i and type ii interferons (ifns). the latter that consists of ifn-γ has been associated with the prom ...201728713838
generation of monoclonal antibodies against ag85a antigen of mycobacterium tuberculosis and application in a competitive elisa for serodiagnosis of bovine tuberculosis.the ag85 complex functions as the main secretory protein of mycobacterium tuberculosis (m. tuberculosis) and bcg. this complex is composed of the proteins, ag85a, ag85b, and ag85c, with ag85a thought to play the largest role within the complex. however, the lack of commercially available monoclonal antibodies (mabs) against ag85a still hinders the biological and applicative research on this protein. in this study, we developed and identified anti-ag85a mabs, and five hybridoma cells were establi ...201728713817
first insight into a nationwide genotypic diversity of mycobacterium tuberculosis among previously treated pulmonary tuberculosis cases in benin, west africa.molecular studies on tuberculosis (tb) are rare in low-resource countries like benin, where data on molecular study on previously treated tb cases is unavailable.201728713434
nanoparticle-formulated curcumin prevents posttherapeutic disease reactivation and reinfection with mycobacterium tuberculosis following isoniazid therapy.curcumin, the bioactive component of turmeric also known as "indian yellow gold," exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. even though considered as a wonder drug pertaining to a myriad of reported benefits, the translational potential of curcumin is limited by its low systemic bioavailability due to its poor intestinal absorption, rapid metabolism, and rapid systemic elimination. therefore, the translational potential of this compound is specif ...201728713372
structural insight into the activation of pkni kinase from m. tuberculosis via dimerization of the extracellular sensor domain.protein kinases play central roles in the survival of mycobacterium tuberculosis within host. here we report the individual high-resolution crystal structures of the sensor domain (in both monomer and dimer forms) and the kinase domain of pkni, a transmembrane protein member of the serine/threonine protein kinases (stpks) family. pkni is the first stpk identified whose sensor domain exists in a monomer-dimer equilibrium. inspection of the two structures of the sensor domain (pkni_sd) revealed co ...201728712808
synthesis and biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents.a library of seventeen novel 1,2,3-triazole derivatives were efficiently synthesized in excellent yields by the popular 'click chemistry' approach and evaluated in vitro for their anti-tubercular activity against mycobacterium tuberculosis h37ra (atcc 25177 strain). among the series, six compounds exhibited significant activity with minimum inhibitory concentration (mic) values ranging from 3.12 to 0.78μg/ml and along with no significant cytotoxicity against mbmdmqs (mouse bone marrow derived ma ...201728712709
striking the right immunological balance prevents progression of tuberculosis.tuberculosis (tb) caused by infection with mycobacterium tuberculosis (mtb) is a major burden for human health worldwide. current standard treatments for tb require prolonged administration of antimycobacterial drugs leading to exaggerated inflammation and tissue damage. this can result in the reactivation of latent tb culminating in tb progression. thus, there is an unmet need to develop therapies that would shorten the duration of anti-tb treatment and to induce optimal protective immune respo ...201728711989
a multistage subunit vaccine effectively protects mice against primary progressive tuberculosis, latency and reactivation.adult tuberculosis (tb) is the main cause of tb epidemic and death. the infection results mainly by endogenous reactivation of latent tb infection and secondarily transmitted by exogenous infection. there is no vaccine for adult tb. to this end, we first chose antigens from a potential antigenic reservoir. the antigens strongly recognized t cells from latent and active tb infections that responded to antigens expressed by mycobacterium tuberculosis cultured under different metabolic states. fusi ...201728711483
breaking transmission with vaccines: the case of tuberculosis.members of the mycobacterium tuberculosis complex (mtbc) have evolved causing tuberculosis (tb) in different mammalian hosts. mtbc ecotypes have adapted to diverse animal species, with m. bovis being the most common cause of tb in livestock. cattle-to-human transmission of m. bovis through ingestion of raw milk was common before introduction of the pasteurization process. tb in humans is mainly caused by m. tuberculosis. this bacterium is considered a genetically clonal pathogen that has coevolv ...201728710848
combining molecular typing and spatial pattern analysis to identify areas of high tuberculosis transmission in a moderate-incidence county in taiwan.in total, 303 randomly selected clinical mycobacterium tuberculosis (mtb) isolates from 303 patients (collected january to december 2012) in central taiwan were examined. the major lineages found were beijing (n = 114, 37.62%), haarlem (n = 76, 25.08%) and east african-indian (eai) (n = 42, 13.86%). notably, younger persons (≤30 years old) were 6.58 times more likely to be infected with a beijing genotype compared to older persons (>70 years) (p < 0.05). combining molecular typing methods and ge ...201728710410
peritoneal tuberculosis as a cause of ascites in a patient with cirrhosis.a 59-year-old portuguese caucasian man with a history of heavy alcohol intake and no significant medical history presented with ascites, weight loss and general malaise. the ascitic fluid analysis showed 921 cells/mm(3) with mononuclear predominance (93.6%), elevated total proteins and a slightly elevated serum-ascites albumin gradient. the abdominal ultrasound confirmed the presence of chronic liver disease with ascites, and additionally on ct there was evidence of peritoneal thickening. on rep ...201728710241
bactericidal impact of ag, zno and mixed agzno colloidal nanoparticles on h37rv mycobacterium tuberculosis phagocytized by thp-1 cell lines.the purpose of this research project was to infection of human macrophages (thp-1) cell lines by h37rv strain of mycobacterium tuberculosis (h37rvmtb) and find out the ratio/dilution of mixture silver (ag nps) and zinc oxide nanoparticles (zno nps) whose ability to eliminate phagocytized bacteria compared to rifampicin. the colloidal ag nps and zno nps were synthesized and their characteristics were evaluated. the thp-1 cell lines were infected with different concentration of h37rvmtb. next, the ...201728710015
drug-resistant tuberculosis coexisting with invasive candidiasis in an immunocompetent 30-year-old woman: a case report.invasive candidiasis coexisting with drug-resistant mycobacterium tuberculosis (dr-tb) in the immunocompetent patient is a rare entity. we report a 30-year-old woman, nondiabetic, who presented to us with complaints of acute onset cough, breathlessness, and fever since 20 days. on thorough investigations, she was diagnosed to be suffering from coexisting drug-resistant tuberculosis and invasive candidiasis. prompt treatment initiated at right time helped us in saving her life. the unique present ...201728709496
band pattern analysis of mutations in rifampicin resistance strain of mycobacterium tuberculosis by line probe assay in patients from delhi, india.the genotype mtbdrplus, a commercial line probe assay (lpa) kit from hain lifescience, germany, is endorsed by india's rntcp program for diagnosis of drtb cases among smear-positive sputum samples. although the lpa has been studied in several laboratories, there is a wide variation in existing m. tuberculosis strains across the globe, and false results can occur due to the presence of unique genetic mutations in different settings.201728709491
endobronchial ultrasound experience in a high tuberculosis prevalence setting.most of the published endobronchial ultrasound-guided transbronchial needle aspiration (ebus-tbna) data are from the western countries, establishing the role of ebus-tbna in the diagnosis and staging of lung cancer. the etiology of mediastinal lymphadenopathy may be different in an ethnic group with a high prevalence of tuberculosis (tb).201728709488
diagnosis of tuberculous meningitis: current scenario from a tertiary neurocare centre in india.tuberculous meningitis (tbm) is a condition that is caused by mycobacterium tuberculosis complex and is difficult to diagnose due to the nonspecificity of the presentations. the study analyzed the different modes of diagnosis available in a developing country set up over a period of five years to understand the diagnostic values of the current conventional and automated methods of diagnosis of tbm among the patients suspected with chronic meningitis.201728709486
parotid tuberculosis.parotid gland tuberculosis is an uncommon manifestation of one of the most common infections even in the developing countries, caused by mycobacterium tuberculosis. there are no specific symptoms or clinical signs of parotid tuberculosis, and such an infection most commonly presents as a slow growing painless parotid mass. because of its rarity, tuberculosis of parotid gland is often mistaken for a malignant growth, and it most commonly gets diagnosed after superficial protidectomy. complete cur ...201728709482
rv3723/luca coordinates fatty acid and cholesterol uptake in mycobacterium tuberculosis.pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. mycobacterium tuberculosis (mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in mtb were previously unknown. here, we identify and determine that the previously uncharacterized protein rv3723/luca, functions to integrate cholesterol and fatty acid uptake in mtb. rv3723/luca interacts ...201728708968
correction: mycobacterium tuberculosis arrests host cycle at the g1/s transition to establish long term infection.[this corrects the article doi: 10.1371/journal.ppat.1006389.].201728708888
rapid diagnosis of extrapulmonary tuberculosis with xpert mycobacterium tuberculosis/rifampicin assay.xpertmycobacterium tuberculosis/rifampicin (xpert mtb/rif) assay has been endorsed by the world health organization (who) for diagnosis of extrapulmonary tuberculosis (eptb), while the sensitivity and specificity have not been fully evaluated. we aimed to evaluate the performance of xpert mtb/rif assay in the detection of different extrapulmonary specimens.201728708053
a review of recent advancements in anti-tubercular molecular hybrids.tuberculosis (tb) accounts for millions of deaths worldwide every year. diverse survival strategies adopted by mycobacterium tuberculosis (mtb) has substantially hindered the existing anti-tb regimen thereby leading to multidrug-resistant (mdr) and extremely drug-resistant (xdr) strains of tb. the steady decrease in current antibiotics' efficacy against these adversities is an indicator that their adequate replenishment in future is almost impossible, placing society on the precipice of a catast ...201728707584
misdiagnosis of tuberculosis associated with some species of nontuberculous mycobacteria by genexpert mtb/rif assay.out of 12 nontuberculous mycobacteria (ntm) species, 5 were identified as mycobacterium tuberculosis (mtb) by genexpert at a bacterial load of 10(6). notably, two species, including m. abscessus and m. smegmatis, were flagged as rif-resistant mtb due to the high c(t) value of probe e. in conclusion, our data have demonstrated that the misdiagnosis of mtb by genexpert assay is observed in five ntm species at a high bacterial load.201728707184
host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis.mycobacterium tuberculosis (mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy of current therapy, and the emergence of drug-resistant strains. this has led to resurgence in attempts to develop new therapeutic strategies/targets against tuberculosis (tb). we show that mtb down-regulates sirtuin 1 (sirt1), a nicotinamide adenine dinucleotide (nad(+))-dependent deacetylase, in monocytes/macrophages, tb animal models, and tb patients with a ...201728707004
reactogenicity to major tuberculosis antigens absent in bcg is linked to improved protection against mycobacterium tuberculosis.mtbvac is a live-attenuated mycobacterium tuberculosis vaccine, currently under clinical development, that contains the major antigens esat6 and cfp10. these antigens are absent from the current tuberculosis vaccine, bcg. here we compare the protection induced by bcg and mtbvac in several mouse strains that naturally express different mhc haplotypes differentially recognizing esat6 and cfp10. mtbvac induces improved protection in c3h mice, the only of the three tested strains reactive to both es ...201728706226
reduced susceptibility of clinical strains of mycobacterium tuberculosis to reactive nitrogen species promotes survival in activated macrophages.drugs such as isoniazid (inh) and pretomanid (prt), used against mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (rns). the aim of this study was to explore variability in intracellular susceptibility to nitric oxide (no) in clinical strains of m. tuberculosis.201728704501
synthesis and in vitro antimycobacterial and antibacterial activity of 8-ome ciprofloxacin-hydrozone/azole hybrids.a series of novel 8-ome ciprofloxacin (cpfx)-hydrazone/azole hybrids were designed, synthesized, and evaluated for their in vitro biological activities. our results reveal that all of the hydrozone-containing hybrids (except for 7) show potency against mycobacterium tuberculosis (mtb) h37rv (minimum inhibitory concentration (mic): <0.5 μm), which is better than the parent drug cpfx, and comparable to moxifloxacin and isoniazid, some of the tested gram-positive strains (mic: 0.06-4 μg/ml), and mo ...201728703766
the role of human host genetics in tuberculosis resistance.tuberculosis (tb) remains a public health problem: the latest estimate of new incident cases per year is a staggering 10.4 million. despite this overwhelming number, the majority of the immunocompetent population can control infection with mycobacterium tuberculosis. the human genome underlies the immune response and contributes to the outcome of tb infection. areas covered: investigations of tb resistance in the general population have closely mirrored those of other infectious diseases and ini ...201728703045
rational design of diagnostic and vaccination strategies for tuberculosis.the development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus calmette-guérin (bcg) as vaccine in humans and animals. bcg_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. we carried out bioinformatics a ...201722358359
detection of genomic mutations in katg, inha and rpob genes of mycobacterium tuberculosis isolates using polymerase chain reaction and multiplex allele-specific polymerase chain reaction.isoniazid (inh) and rifampin (rif) are the most effective first line antibiotics against mycobacterium tuberculosis. mutations in several genes determine resistance of m. tuberculosis to inh, with the most common gene target of katg, and resistance to rif is due to mutation in rpob gene. the aim of present study was to assess the mutations in the regions related to rif and inh resistance.201722358357
passenger contact investigation associated with a transport driver with pulmonary tuberculosis.in october 2008, pulmonary tuberculosis (tb) was diagnosed in a driver who had transported 762 passengers in the district of columbia metropolitan area during his infectious period. a passenger contact investigation was conducted by the six public health jurisdictions because of concern that some passengers might be infected with hiv or have other medical conditions that put them at increased risk for developing tb disease if infected.201722379220
template registration with missing parts: application to the segmentation of m. tuberculosis infected lungs.many techniques have been proposed to segment organs from images, however the segmentation of diseased organs remains challenging and frequently requires lots of user interaction. the challenge consists of segmenting an organ while its appearance and its shape vary due to the presence of the disease in addition to individual variations. we propose a template registration technique that can be used to recover the complete segmentation of a diseased organ from a partial segmentation. the usual tem ...201726146531
synthesis, structure, and tuberculostatic activity of dimethyl benzoylcarbonohydrazonodithioates.new dimethyl benzoylcarbonohydrazonodithioates were obtained by cs2 addition to arylcarboxylic acid hydrazides and methylation of the formed adduct. the new derivatives were tested for their activity against mycobacterium tuberculosis. some compounds exhibited high activity toward sensitive and resistant strains.201726166854
incorporating user input in template-based segmentation.we present a simple and elegant method to incorporate user input in a template-based segmentation method for diseased organs. the user provides a partial segmentation of the organ of interest, which is used to guide the template towards its target. the user also highlights some elements of the background that should be excluded from the final segmentation. we derive by likelihood maximization a registration algorithm from a simple statistical image model in which the user labels are modeled as b ...201726146532
previous use of quinolones: a surrogate marker for first line anti-tuberculosis drugs resistance in hiv-infected patients?drug resistant mycobacterium tuberculosis causes much higher rates of treatment toxicity, failure or relapse, and mortality. we determined the drug resistant profile of mycobacterium tuberculosis strains isolated from a population of hiv-infected patients in southern brazil and studied the potential factors associated with resistance.201722552455
characterization of gyra and gyrb mutations and fluoroquinolone resistance in mycobacterium tuberculosis clinical isolates from hubei province, china.the study aimed to investigate gyra and gyrb mutations in mycobacterium tuberculosis (mtb) clinical strains from 93 patients with pulmonary tuberculosis in hubei province, china, and analyze the association between mutation patterns of the genes and ofloxacin resistance level.201722552454
fitting birth-death processes to panel data with applications to bacterial dna fingerprinting.continuous-time linear birth-death-immigration (bdi) processes are frequently used in ecology and epidemiology to model stochastic dynamics of the population of interest. in clinical settings, multiple birth-death processes can describe disease trajectories of individual patients, allowing for estimation of the effects of individual covariates on the birth and death rates of the process. such estimation is usually accomplished by analyzing patient data collected at unevenly spaced time points, r ...201726702330
effectiveness of the bdprobetec et system for detection of mycobacterium tuberculosis complex in sputum and bronchoalveolar lavage specimens.the diagnostic efficacy of the bdprobetec et mycobacterium tuberculosis (mtb) complex direct detection assay (dtb) performed on bronchoalveolar lavage (bal) specimens and sputum smears was compared with acid-fast bacilli (afb) smear microscopy.201722729191
interferon-γ release assays for the diagnosis of mycobacterium tuberculosis infection in children: a literature review.the role of interferon-gamma release assays (igras) for immunologic diagnosis of tuberculosis in children is under debate. we carried out a narrative review on the studies on igras in paediatric populations. a literature search was conducted using multiple keywords and standardized terminology in medline, embase and cochrane databases, up to january 27th, 2011. study quality was assessed using the moose checklist and results of relevant studies were summarized. sixty-seven paediatric studies (st ...201722697065
interferon-γ release assays for the diagnosis of mycobacterium tuberculosis infection in children: a systematic review and meta-analysis.data regarding the use of interferon-gamma release assays (igras) for tuberculosis diagnosis are accumulating. we systematically searched pubmed, embase and cochrane and performed pooled estimates of sensitivity and specificity of quantiferon-tb gold in tube (qft-g-it) and t-spot.tb compared to tuberculin skin test (tst). for studies assessing sensitivity, children had to have active tuberculosis. specificity data were derived from children classified as non-infected. eleven studies were include ...201723058005
copper and antibiotics: discovery, modes of action, and opportunities for medicinal applications.copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. however, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including dna, lipids, and proteins. to restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copp ...201728528648
molecular diagnosis of tubercular lymphadenopathy from fine-needle aspirates in pediatric patients.the diagnosis of peripheral tubercular lymphadenopathy (tbln) in pediatric patients is often a challenge because features evident on fine-needle aspiration cytology (fnac) or tissue biopsy can be deceptive for the reason that they result from an immunological response. this study aimed to evaluate polymerase chain reaction (pcr) for mycobacterium tuberculosis complex (mtbc) in pediatric patients under clinical suspicion for tbln and to assess its role in the evaluation of cases cytodiagnosed as ...201728528339
immuno-pcr, a new technique for the serodiagnosis of tuberculosis.rapid and accurate diagnosis of tuberculosis (tb) is essential to control the disease. the conventional microbiological tests have limitations and there is an urgent need to devise a simple, rapid and reliable point-of-care (poc) test. the failure of tb diagnostic tests based on antibody detection due to inconsistent and imprecise results has stimulated renewed interest in the development of rapid antigen detection methods. however, the world health organization (who) has emphasized to continue ...201728527886
new 1-hydroxy-2-thiopyridine derivatives active against both replicating and dormant mycobacterium tuberculosis.tuberculosis (tb) treatment is confounded by the range of metabolic states displayed by mycobacterium tuberculosis, by the long duration required and by the increasing prevalence of drug-resistant strains. latent tb infection is especially difficult to treat due to the phenotypic antibiotic resistance of non-replicating m. tuberculosis. therefore, the development of new drugs effective against both active and latent tb infection is needed. new 1-hydroxy-2-thiopyridine derivatives were synthesize ...201728527650
[identification of the mycobacterium tuberculosis beijing lineage in ecuador].mycobacterium tuberculosis beijing lineage isolates are considered to be especially virulent, transmissible and prone to acquire resistances. beijing strains have been reported worldwide, but studies in latin america are still scarce. the only multinational study performed in the region indicated a heterogeneous distribution for this lineage, which was absent in chile, colombia and ecuador, although further studies found the lineage in chile and colombia.201728527287
[performance of led fluorescence microscopy for the detection of acid-fast bacilli from respiratory samples in peripheral laboratories in argentina].light-emitting diode fluorescence microscopy (led-fm) has been endorsed by the world health organization (who) for tuberculosis diagnosis, but its accuracy in hiv-infected patients remains controversial, and only some few studies have explored procedural factors that may affect its performance.201728527280
[prevalence of mycobacterium tuberculosis resistance to quinolones and injectables in colombia, 2012-2013].tuberculosis is a health problem worldwide. the world health organization estimated 9.6 million new cases and 480,000 multirresistant cases for 2014. the assessment of resistance to quinolones and injectables was implemented only a few years ago, so its prevalence is not known.201728527253
[characterization of clinical isolates of mycobacterium tuberculosis from hiv positive individuals in colombia, 2012].one third of the increase in tuberculosis cases is attributed to the spread of hiv. in 2012, 1,397 hiv-associated tuberculosis cases were reported in colombia, i.e., 11.8% of the total cases. molecular epidemiology tools help to understand the transmission of tuberculosis.201728527252
[description of mycobacterium tuberculosis mutations conferring resistance to rifampicin and isoniazid detected by genotype® mtbdrplus v.2 in colombia].the genotype®mtbdrplusv.2 assay is a molecular technique endorsed by the world health organization and the pan american health organization that allows for the identification of the mycobacterium tuberculosis complex and the detection of mutations in the rpoβ gene for rifampicin resistance, and katg and inha genes for isoniazid resistance. due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these ...201728527245
adoptive transfer of phosphoantigen-specific γδ t cell subset attenuates mycobacterium tuberculosis infection in nonhuman primates.the dominant vγ2vδ2 t cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. despite the discovery of γδ t cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the vγ2vδ2 t cell subset is protective against mycobacterium tuberculosis and other infections. in this study, we used an adoptive cell-transfer strategy to define the protective role of vγ2vδ2 t cells in a primate tuberculosis (tb) model. vγ2vδ2 t cells for adoptive trans ...201728526681
challenges in the estimation of the annual risk of mycobacterium tuberculosis infection in children aged under 5 years.accurate estimates of mycobacterium tuberculosis (m.tb) infection in young children provide a critical indicator of on-going community m.tb transmission. cross reactions due to infection with environmental mycobacteria and/or bacille calmette-guérin (bcg) vaccination compromise the estimates derived from population-level tuberculin skin test surveys using traditional cut-off methods. newer statistical approaches are prone to failure of model convergence, especially in settings where the prevalen ...201728525582
unaffected reaction level in tuberculin skin test by long-term therapy with tumor necrosis factor inhibitors for rheumatoid arthritis.the tuberculin skin test (tst) is used to diagnose tuberculosis; however, the influence of tumor necrosis factor (tnf) inhibitors on the test is unclear. this study investigated whether therapy with tnf inhibitors suppresses the tst reaction due to immunosuppression or whether the tst reaction increases due to reactivation of latent mycobacterium tuberculosis infection.201728524434
discovery of fluorine-containing benzoxazinyl-oxazolidinones for the treatment of multidrug resistant tuberculosis.a novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. compound 21 exhibited not only outstanding in vitro activity with a mic value of 0.25-0.50 μg/ml against drug-susceptible h37rv strain and two clinically isolated drug-resistant mycobacterium tuberculosis strains, but also acceptable in vitro adme/t properties. moreover, this compound displayed ex ...201728523106
evaluation of xpert mtb/rif assay performance in the diagnosis of abdominal tuberculosis.the use of genetic probes for the diagnosis of pulmonary tuberculosis (tb) has been well described. however, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. we therefore assessed the diagnostic utility of the xpert mycobacterium tuberculosis/rifampicin (mtb/rif) assay, and estimated the prevalence of multidrug-resistant (mdr) tb in the indian population.201728522948
knowns and unknowns of membrane lipid synthesis in streptomycetes.bacteria belonging to the genus streptomyces are among the most prolific producers of antibiotics. research on cellular membrane biosynthesis and turnover is lagging behind in streptomyces compared to related organisms like mycobacterium tuberculosis. while natural products discovery in streptomyces is evidently a priority in order to discover new antibiotics to combat the increase in antibiotic resistant pathogens, a better understanding of this cellular compartment should provide insights into ...201728522365
potential of multi-component antigens for tuberculosis diagnosis.tuberculosis is one of the top ten causes of deaths worldwide. the cause of tuberculosis is a bacterium, mycobacterium tuberculosis, which has been surviving for centuries. immunological tests based on detecting the presence of antibodies in the sera of active tb patients against various antigens of m. tuberculosis are useful for diagnosis of tb and offer simple, rapid and cost effective methods most suitable for poor and developing countries. several recombinant antigens have been reported so f ...201728522247
disseminated bacillus calmette-guérin osteomyelitis in twin sisters related to stat1 gene deficiency.mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as bacillus calmette-guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. since 1996, 9 genes including 7 autosomal ( stat1, ifngr1, ifngr2, il12b, il12rb1, isg15, and irf8) and 2 x-linked genes ( nemo and cybb) have been identified. allelic heterogeneity ...201728521627
bis(diphenylphosphino)amines-containing ruthenium cymene complexes as potential anti-mycobacterium tuberculosis agents.several ruthenium complexes have been investigated regarding anti-mycobacterium tuberculosis (anti-mtb) activity, with some diphosphine-containing ruthenium complexes comparable to first and second line drugs. however, to the best of our knowledge, there is no pnp-containing ruthenium complexes applied as metallodrugs. thus, this study focused on the synthesis, characterization and anti-mtb activity of a new series of coordination compounds with general formula [rucl(η(6)-p-cymene)(pn(r)p)]x (r= ...201728521188
the changing epidemiology of spinal tuberculosis: the influence of international immigration in catalonia, 1993-2014.the overall incidence of spinal tuberculosis (tb) appears to be stable or declining in most european countries, but with an increasing proportion of cases in the foreign-born populations. we performed a retrospective observational study (1993-2014), including all cases of spinal tb diagnosed at a barcelona hospital to assess the epidemiological changes. fifty-four episodes (48·1% males, median age 52 years) of spinal tb were diagnosed. the percentage of foreign-born residents with spinal tb incr ...201728516818
the history of tuberculosis: from the first historical records to the isolation of koch's bacillus.tuberculosis (tb) is a contagious, infectious disease, due to mycobacterium tuberculosis (mt) that has always been a permanent challenge over the course of human history, because of its severe social implications. it has been hypothesized that the genus mycobacterium originated more than 150 million years ago. in the middle ages, scrofula, a disease affecting cervical lymph nodes, was described as a new clinical form of tb. the illness was known in england and france as "king's evil", and it was ...201728515626
characterization of a secretory hydrolase from mycobacterium tuberculosis sheds critical insight into host lipid utilization by m. tuberculosis.mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. to survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. for example, m. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. m. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question aris ...201728515317
pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immunopathogenesis: emerging concepts and perspectives.pattern recognition receptors (prrs) play a central role in the recognition of numerous pathogens, including mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. besides toll like receptors, c-type lectin receptors and nod like receptors are now being recognized for their involvement in inducing immune response against m. tuberculosis infection. although, a functional redundancy of the prrs has also been reported in many studies, emerging evidences support ...201728514713
evaluation of improved is6110 lamp assay for diagnosis of pulmonary and extra pulmonary tuberculosis.in the present study, is6110 loop mediated isothermal amplification (lamp) assay was modified using dutp-ung (uracil-dna n-glycosylase) strategy to prevent carryover contamination, and was evaluated using clinical specimens. the clinical specimens were collected from 236 suspected patients of pulmonary tuberculosis and 315 specimens of suspected patients of extra pulmonary tuberculosis. dna was extracted from specimens and used as template for nucleic acid amplification. the results were evaluat ...201728514671
fragment screening against the ethr-dna interaction by native mass spectrometry.native nanoelectrospray ionization mass spectrometry is an underutilized technique for fragment screening. in this study, the first demonstration is provided of the use of native mass spectrometry for screening fragments against a protein-dna interaction. ethr is a transcriptional repressor of etha expression in mycobacterium tuberculosis (mtb) that reduces the efficacy of ethionamide, a second-line antitubercular drug used to combat multidrug-resistant mtb strains. a small-scale fragment screen ...201728513917
clinical and bacteriological characteristics associated with clustering of multidrug-resistant tuberculosis.the impact of the genetic characteristics of mycobacterium tuberculosis on the clustering of multidrug-resistant tuberculosis (mdr-tb) has not been analyzed together with clinical and demographic characteristics.201728513421
the role of esx-1 in mycobacterium tuberculosis pathogenesis.in this article, we have described several cellular pathological effects caused by the mycobacterium tuberculosis esx-1. the effects include induction of necrosis, nod2 signaling, type i interferon production, and autophagy. we then attempted to suggest that these pathological effects are mediated by the cytosolic access of m. tuberculosis-derived materials as a result of the phagosome-disrupting activity of the major esx-1 substrate esat-6. such activity of esat-6 is most likely due to its pore ...201728513416
effect of trichilia monadelpha (meliaceae) extracts on bone histomorphology in complete freund's adjuvant-induced arthritis.this study aimed to assess the effect of petroleum ether extract (pee), ethyl acetate extract (ethe), and ethanol extract (eae) of trichilia monadelpha stem bark on bone histomorphology in arthritis.201728512599
synthesis, antimycobacterial activity and docking study of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1h)-one derivatives and related hydrazide-hydrazones.a new convenient method for preparation of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1h)-one derivatives 5b-g and coumarin containing hydrazide-hydrazone analogues 4a-e was presented. the antimycobacterial activity against reference strain mycobacterium tuberculosis h37rv and cytotoxicity against the human embryonic kidney cell line hek-293 were tested in vitro. all compounds demonstrated significant minimum inhibitory concentrations (mic) ranging 0.28-1.69μm, which were comparable to those of ison ...201728512022
diagnostic performance of anyplex ii mtb/mdr/xdr for detection of resistance to first and second line drugs in mycobacterium tuberculosis.genotypic methods have considerably improved the diagnosis of multidrug-resistant (mdr) tuberculosis. one of these tests is anyplex ii mtb/mdr/xdr (anyplex). our aim was to evaluate the diagnostic performance of this multiplex pcr.201728511895
sputum microscopy with fluorescein diacetate predicts tuberculosis infectiousness.sputum from patients with tuberculosis contains subpopulations of metabolically active and inactive mycobacterium tuberculosis with unknown implications for infectiousness.201728510693
conjugation reaction with 8-arm peg markedly improves the immunogenicity of mycobacterium tuberculosis cfp10-tb10.4 fusion protein.mycobacterium tuberculosis (mtb) is a serious fatal pathogen responsible for tuberculosis (tb). effective vaccination is highly desired for immunoprotection against mtb infection. cfp10 and tb10.4 are two important immunodominant mtb-secreted protein antigens, which suffer from poor immunogenicity. thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. a cfp10-tb10.4 fusion protein (ct) was used as the antigen in the present study. conjugatio ...201728510418
the phytochemical bergenin enhances t helper 1 responses and anti-mycobacterial immunity by activating the map kinase pathway in macrophages.tuberculosis (tb) remains one of the greatest health concerns worldwide, which has hindered socioeconomic development in certain parts of the world for many centuries. although current tb therapy, "directly observed treatment short-course," is effective, it is associated with unwanted side effects and the risk for the generation of drug-resistant organisms. the majority of infected individuals successfully confine the mycobacterial organisms and remain asymptotic unless immune responses are pert ...201728507951
the mycobacterium tuberculosis mmpl11 cell wall lipid transporter is important for biofilm formation, intracellular growth, and nonreplicating persistence.the mycobacterial cell wall is crucial to the host-pathogen interface, because it provides a barrier against antibiotics and the host immune response. in addition, cell wall lipids are mycobacterial virulence factors. the mycobacterial membrane protein large (mmpl) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and mycobacterium tuberculosis pathogenesis. mmpl3 and mmpl11 are conserved across pathogenic and nonpathogenic mycobacteria, a feature co ...201728507063
chloroquine enhances the antimycobacterial activity of isoniazid and pyrazinamide by reversing inflammation-induced macrophage efflux.mycobacterium tuberculosis (mtb) is notorious for persisting within host macrophages. efflux pumps decrease intracellular drug levels, thus fostering persistence of mtb during therapy. isoniazid (inh) and pyrazinamide (pza) are substrates of the efflux pump breast cancer resistance protein-1 (bcrp-1), which is inhibited by chloroquine (cq). in this study, bcrp-1 was found to be expressed on macrophages of human origin and on foamy giant cells at the site of mtb infection. in the current in vitro ...201728506804
comparison of antibody responses against mycobacterium tuberculosis antigen rv0679c in tuberculosis patients from the endemic and non-endemic regions of the beijing genotype: a case control study.strains of the beijing genotype of mycobacterium tuberculosis (mtb) are reportedly associated with the virulence of tuberculosis (tb) infection, unfavorable outcomes of anti-tb treatment, and the global tb pandemic. rv0679c, a hypothetical membrane protein related to host cell invasion, has a beijing genotype-specific mutation at residue 142 (asn142lys). antigenicity differences between rv0679c-asn142 (n-type) and rv0679c-lys142 (k-type) have been previously observed in mice antigen-antibody res ...201728506215
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