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[application of gene xpert mycobacterium tuberculosis dna and resistance to rifampicin assay in the rapid detection of tuberculosis in children].to detect mycobacterium tuberculosis (mtb) and rifampin resistance of the clinical specimens in children by xpert mtb dna and resistance to rifampicin(mtb/rif) detection system, and evaluate the application value of this method in children with tuberculosis.201627143080
effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.mycobacterium tuberculosis (mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. in this scenario, the use of usnic acid (ua), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (mdr-tb) therapy. thus the aim of this study was to evaluate the effect of the encapsulation of ua into liposomes, as well as its combination with antituberculous agents such as rif ...201627143488
high rate of drug resistance among tuberculous meningitis cases in shaanxi province, china.the clinical and mycobacterial features of tuberculous meningitis (tbm) cases in china are not well described; especially in western provinces with poor tuberculosis control. we prospectively enrolled patients in whom tbm was considered in shaanxi province, northwestern china, over a 2-year period (september 2010 to december 2012). cerebrospinal fluid specimens were cultured for mycobacterium tuberculosis; with phenotypic and genotypic drug susceptibility testing (dst), as well as genotyping of ...201627143630
a 22-year-old man with pleural tuberculosis associated hydropneumothorax: case report and literature review.a 22-year-old asian male presented with fever, non-productive cough, right-sided pleuritic chest pain and was found to have a large right hydropneumothorax. a chest tube was placed. pleural fluid analysis revealed a lymphocytic predominant exudate and he was subsequently started on four-drug daily anti-tuberculosis therapy (isoniazid, ethambutol, rifampin, pyrazinamide). pleural biopsy revealed acid-fast bacilli. given his persistent pleural effusion, he was given four doses of intrapleural tiss ...201627144114
unravelling the secrets of mycobacterial cidality through the lens of antisense.one of the major impediments in anti-tubercular drug discovery is the lack of a robust grammar that governs the in-vitro to the in-vivo translation of efficacy. mycobacterium tuberculosis (mtb) is capable of growing both extracellular as well as intracellular; encountering various hostile conditions like acidic milieu, free radicals, starvation, oxygen deprivation, and immune effector mechanisms. unique survival strategies of mtb have prompted researchers to develop in-vitro equivalents to simul ...201627144597
novel cephalosporins selectively active on nonreplicating mycobacterium tuberculosis.we report two series of novel cephalosporins that are bactericidal to mycobacterium tuberculosis alone of the pathogens tested, which only kill m. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. the two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at c-2 of the cephalosporin ring system, a positio ...201627144688
resistant tuberculosis in maranhão, brazil: a case series.mycobacterium tuberculosis multidrug resistance, especially against rifampicin and isoniazid, places pulmonary tuberculosis in the list of emerging diseases. the misuse of therapeutic regimens is one of its main predisposing factors.201627145827
an overview of phytotherapeutic approaches for the treatment of tuberculosis.tuberculosis (tb) is highly infectious disease causing morbidity and death. its causative organism is a contagious bacterium, mycobacterium tuberculosis. the incidence of tuberculosis is increasing worldwide due to the emergence of drug resistance bacteria. the resistance is being developed in mycobacterium tuberculosis against both the first line as well as the second line drugs used for the treatment. the tuberculosis control programme is being complicated and failed to get the desired impact ...201727145855
mycobacterium cytidylate kinase appears to be an undruggable target.new and improved drugs against tuberculosis are urgently needed as multi-drug-resistant forms of the disease become more prevalent. mycobacterium tuberculosis cytidylate kinase is an attractive target for screening due to its essentiality and different substrate specificity to the human orthologue. however, we selected the mycobacterium smegmatis cytidylate kinase for screening because of the availability of high-resolution x-ray crystallographic data defining its structure and the high likeliho ...201627146385
anti-tubercular and antioxidant activities of c-glycosyl carbonic anhydrase inhibitors: towards the development of novel chemotherapeutic agents against mycobacterium tuberculosis.during the treatment of tuberculosis infection, oxidative stress due to anti-tubercular drugs may result in tissue inflammation. it was suggested that treatment with antioxidant drugs could be beneficial as an adjunct to anti-tuberculosis drug therapy. recently our group has shown that several c-glycosides are inhibitors of mycobacterium tuberculosis β-carbonic anhydrases (cas, ec 4.2.1.1). in an effort to develop novel chemotherapeutic agents against tuberculosis, the anti-tubercular and antiox ...201627146440
identification of potential antituberculosis drugs through docking and virtual screening.tuberculosis is the most prominent contagious disease and needs the new targets and drugs identification. target identification and validation is a crucial step in drug discovery process. in mycobacterium tuberculosis, decaprenyl-phosphoryl-β-d-ribose 2'-oxidase is a potential target for antitubercular chemotherapy. it is encoded by genes dpre1 (rv3790) and dpre2 (rv3791). three-dimensional (3d) structure prediction of selected target (461 amino acid residues) was intent by homology modeling usi ...201627147082
mycobacterium tuberculosis pe13 (rv1195) manipulates the host cell fate via p38-erk-nf-κb axis and apoptosis.pe/ppe family proteins are mycobacteria unique molecules, named after their n-terminal conserved pe (pro-glu) and ppe (pro-pro-glu) domains. mycobacterium tuberculosis (mtb) pe family gene encoded cell surface proteins are previously reported to be involved in virulence and interaction with host. to explore the role of a novel pe member (pe13, rv1195), m. smegmatis was used as surrogate host. the study showed that rv1195 was a cell wall associated protein. rv1195 can enhance the survival of reco ...201627147522
insufficient generation of mycobactericidal mediators and inadequate level of phagosomal maturation are related with susceptibility to virulent mycobacterium tuberculosis infection in mouse macrophages.tuberculosis is caused by mycobacterium tuberculosis infection, and it remains major life-threatening infectious diseases worldwide. although, m. tuberculosis has infected one-third of the present human population, only 5-10% of immunocompetent individuals are genetically susceptible to tuberculosis. all inbred strains of mice are susceptible to tuberculosis; however, some mouse strains are much more susceptible than others. in a previous report, we showed that th1-mediated immunity was not resp ...201627148227
immunometabolism in tuberculosis.immunometabolism, the study of the relationship between bioenergetic pathways and specific functions of immune cells, has recently gained increasing appreciation. in response to infection, activation of the host innate and adaptive immune cells is accompanied by a switch in the bioenergetic pathway from oxidative phosphorylation to glycolysis, a metabolic remodeling known as the warburg effect, which is required for the production of antimicrobial and pro-inflammatory effector molecules. in this ...201627148269
g1-4a, a polysaccharide from tinospora cordifolia inhibits the survival of mycobacterium tuberculosis by modulating host immune responses in tlr4 dependent manner.rapid emergence of drug resistance in mycobacterium tuberculosis (mtb) is a major health concern and demands the development of novel adjunct immunotherapeutic agents capable of modulating the host immune responses in order to control the pathogen. in the present study, we sought to investigate the immunomodulatory effects of g1-4a, a polysaccharide derived from the indian medicinal plant tinospora cordifolia, in in-vitro and aerosol mouse models of mtb infection. g1-4a treatment of mtb infected ...201627148868
benzothiazole derivative as a novel mycobacterium tuberculosis shikimate kinase inhibitor: identification and elucidation of its allosteric mode of inhibition.mycobacterium tuberculosis shikimate kinase (mtb-sk) is a key enzyme involved in the biosynthesis of aromatic amino acids through the shikimate pathway. since it is proven to be essential for the survival of the microbe and is absent from mammals, it is a promising target for anti-tb drug discovery. in this study, a combined approach of in silico similarity search and pharmacophore building using already reported inhibitors was used to screen a procured library of 20,000 compounds of the commerc ...201627149193
identification of a non-pentapeptide region associated with rapid mycobacterial evolution.a large portion of the coding capacity of mycobacterium tuberculosis is devoted to the production of proteins containing several copies of the pentapeptide-2 repeat, namely the pe/ppe_mptr proteins. protein domain repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as dna and rna. they are not as common in prokaryotes, compared to eukaryotes, but the enrichment of pentapeptide-2 repeats in mycobacteria constitutes ...201627149271
mapping of mycobacterium tuberculosis complex genetic diversity profiles in tanzania and other african countries.the aim of this study was to assess and characterize mycobacterium tuberculosis complex (mtbc) genotypic diversity in tanzania, as well as in neighbouring east and other several african countries. we used spoligotyping to identify a total of 293 m. tuberculosis clinical isolates (one isolate per patient) collected in the bunda, dar es salaam, ngorongoro and serengeti areas in tanzania. the results were compared with results in the sitvit2 international database of the pasteur institute of guadel ...201627149626
sulphur-containing heterocycles as antimycobacterial agents: recent advances in thiophene and thiadiazole derivatives.the global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. recent development is focused mainly on heterocyclic molecules. in many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. this review highlights the recent progress ...201627150373
comparative proteomic analyses of avirulent, virulent, and clinical strains of mycobacterium tuberculosis identify strain-specific patterns.mycobacterium tuberculosis is an adaptable intracellular pathogen, existing in both dormant as well as active disease-causing states. here, we report systematic proteomic analyses of four strains, h37ra, h37rv, and clinical isolates bnd and jal, to determine the differences in protein expression patterns that contribute to their virulence and drug resistance. resolution of lysates of the four strains by liquid chromatography, coupled to mass spectrometry analysis, identified a total of 2161 prot ...201627151218
new agents for the treatment of drug-resistant mycobacterium tuberculosis.inadequate dosing and incomplete treatment regimens, coupled with the ability of the tuberculosis bacilli to cause latent infections that are tolerant of currently used drugs, have fueled the rise of multidrug-resistant tuberculosis (mdr-tb). treatment of mdr-tb infections is a major clinical challenge that has few viable or effective solutions; therefore patients face a poor prognosis and years of treatment. this review focuses on emerging drug classes that have the potential for treating mdr-t ...201627151308
repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs.the number of cases of drug-resistant mycobacterium tuberculosis, the causative agent of tuberculosis (tb), has risen rapidly in recent years. this has led to the resurgence in repurposing existing drugs, such as non-steroidal anti-inflammatory drugs (nsaids), for anti-tb treatment.201627151954
improving the n-terminal diversity of sansanmycin through mutasynthesis.sansanmycins are uridyl peptide antibiotics (upas), which are inhibitors of translocase i (mray) and block the bacterial cell wall biosynthesis. they have good antibacterial activity against pseudomonas aeruginosa and mycobacterium tuberculosis strains. the biosynthetic gene cluster of sansanmycins has been characterized and the main biosynthetic pathway elucidated according to that of pacidamycins which were catalyzed by nonribosomal peptide synthetases (nrpss). sananmycin a is the major compou ...201627154005
early secreted antigenic target of 6 kda of mycobacterium tuberculosis stimulates macrophage chemoattractant protein-1 production by macrophages and its regulation by p38 mitogen-activated protein kinases and interleukin-4.early secreted antigenic target of 6 kda (esat-6), the major virulence factor of mycobacterium tuberculosis, affects host immunity and the formation of granulomas likely through inflammatory cytokines. to understand its role in this regard further, we investigated the effect of esat-6 on macrophages by determining the production of macrophage chemoattractant protein (mcp)-1, a major chemokine associated with tuberculosis pathogenesis, by murine bone marrow-derived macrophages (bmdms) and its reg ...201627154637
mycobacterium tuberculosis rv1400c encodes functional lipase/esterase.lipases catalyze the hydrolysis of triglycerides (tag). open reading frames (orf) predicted to encode enzymes involved in fatty acids breakdown are abundant in mycobacterium tuberculosis genome. to define the function of m. tuberculosis rv1400c (lipi), a putative hormone sensitive lipase (hsl) subfamily orf, the rv1400c was cloned, expressed and purified in escherichia coli as fusion protein. the purified lipi preferred short carbon chain substrates with an optimal activity at 37 °c/ph 8.0 and s ...201727154903
antibacterial activities of medicinal plants used in mexican traditional medicine.we provide an extensive summary of the in vitro antibacterial properties of medicinal plants popularly used in mexico to treat infections, and we discuss the ethnomedical information that has been published for these species.201627155134
capilia™ tb-neo assay: a new tool for rapid distinction between tuberculous and non-tuberculous mycobacteria.the ability to rapidly distinguish between mycobacterium tuberculosis complex (mtc) and non-tuberculous mycobacteria (ntm) is critical in clinical practice.201627155177
distribution and association of mycobacterium tuberculosis cas lineage with multidrug resistance in north india.a tertiary care hospital in north india.201627155185
a diagnosis of disseminated tuberculosis based on knee arthroscopic guided synovial biopsy in the context of monoarthritis.accounting for 2.2-4.7% of all tuberculosis cases in europe and usa and around 10-15% of extra-pulmonary tuberculosis cases, osteoarticular tuberculosis tends to be chronic, slowly progressive and destructive. we report the case of an 81-year-old male with 3 weeks of progressively worsening pain, swelling and limited range of motion of the left knee. a knee arthroscopy was performed for synovial biopsy at our department revealing diffuse synovitis with scarce villi formation. the positive polyme ...201627155318
immune oxysterols: role in mycobacterial infection and inflammation.infection remains an important cause of morbidity and mortality. natural defenses to infection are mediated by intrinsic/innate and adaptive immune responses. while our understanding is considerable it is incomplete and emerging areas of research such as those related to the immune-metabolic axis are only beginning to be appreciated. there is increasing evidence showing a connection between immune signalling and the regulation of sterol and fatty acid metabolism. in particular, metabolic interme ...201627155346
host immune responses to antigens derived from a predominant strain of mycobacterium tuberculosis.beijing strain of mycobacterium tuberculosis (m. tb) is characterized by a high incidence of transmission, relapse, and drug resistance. this study aimed to determine host immune responses to antigens derived from the beijing/k strain which has been highly prevalent in tuberculosis (tb) outbreaks in south korea.201627155519
does concurrent use of some botanicals interfere with treatment of tuberculosis?millions of individuals with active tb do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for prophylaxis and treatment of tb, as suggested by results of a recent clinical trial of the south african botanical sutherlandia frutescens (l.) r. br. (sutherlandia). here we provide a ...201627155670
insights into rpob clinical mutants in mediating rifampicin resistance in mycobacterium tuberculosis.rifampicin (rif) an essential first-line anti-tuberculosis (tb) drug, resistance to rif is a potential threat to tb control program and widely considered as surrogate marker for detection of multi-drug resistant-tb (mdr-tb), molecular understanding of which is the utmost need of the hour. mutations at rif resistance-determining region (rrdr) of 81-bp in the rpob gene coding for β subunit or rpob protein is the major cause of rif resistance in mycobacterium tuberculosis (mtb). mutation at positio ...201627155814
thermostability of ifn-γ and ip-10 release assays for latent infection with mycobacterium tuberculosis: a tbnet study.interferon-γ (ifn-γ) inducible protein 10kd (ip-10) and ifn-γ release assays (igras) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with mycobacterium tuberculosis. incubation at higher temperatures could affect ifn-γ and ip-10 responsiveness in order to improve the performance of ip-10 release assays and igras.201627156612
impaired nk cells' activity and increased numbers of cd4 + cd25+ regulatory t cells in multidrug-resistant mycobacterium tuberculosis patients.multidrug-resistant tuberculosis (mdr-tb) often causes persistent infection and chemotherapy failure, which brings heavy burden of society and family. many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. the presence of regulatory t cells (tregs) is thought to be an important mechanism that tb successfully evades the immune system. tregs play a central role in the prevention of autoimmunity and in the control of immune responses. the role of ...201627156613
tuberculosis or sarcoidosis: opposite ends of the same disease spectrum?tuberculosis and sarcoidosis are chronic systemic diseases that have similar pulmonary and extra-pulmonary manifestations. multiple studies have found an epidemiological, molecular, and immunological link between the two. it has been suggested that mycobacterium tuberculosis could be a common pathophysiologic mechanism for tuberculosis and sarcoidosis, and that both clinical entities can trigger similar immunological response in patients. due to this close association, together with possible coe ...201627156614
neuroleptic drugs in the treatment of tuberculosis: minimal inhibitory concentrations of different phenothiazines against mycobacterium tuberculosis.due to an increase of drug resistant tb, alternative drugs that are not currently listed in the who guidelines on mdr tb treatment are currently being evaluated. our group tested 100 susceptible, 20 mdr and 2 xdr mtb strains against the phenothiazine derivatives thioridazine, trifluoperazine and triflupromazine. mic testing was performed on middlebrook 7h10 agar and was defined as the lowest drug concentration that inhibits ≥99% of the bacterial population. we confirm very good in vitro activity ...201627156615
mycobacterium tuberculosis infection and vaccine development.following hiv/aids, tuberculosis (tb) continues to be the second most deadly infectious disease in humans. the global tb prevalence has become worse in recent years due to the emergence of multi-drug resistant (mdr) and extensively-drug resistant (xdr) strains, as well as co-infection with hiv. although bacillus calmette-guérin (bcg) vaccine has nearly been used for a century in many countries, it does not protect adult pulmonary tuberculosis and even causes disseminated bcg disease in hiv-posit ...201627156616
cloning, expression and characterization of histidine-tagged biotin synthase of mycobacterium tuberculosis.the emergence of mycobacterium tuberculosis strains that are resistant to the current anti-tuberculosis (tb) drugs necessitates a need to develop a new class of drugs whose targets are different from the current ones. m. tuberculosis biotin synthase (mtbbs) is one such target that is essential for the survival of the bacteria. in this study, mtbbs was cloned, overexpressed and purified to homogeneity for biochemical characterization. it is likely to be a dimer in its native form. its ph and temp ...201627156617
longitudinal whole genome analysis of pre and post drug treatment mycobacterium tuberculosis isolates reveals progressive steps to drug resistance.tuberculosis (tb) is one of the leading causes of death due to an infectious disease in the world. understanding the mechanisms of drug resistance has become pivotal in the detection and treatment of newly emerging resistant tb cases. we have analyzed three pairs of mycobacterium tuberculosis strains pre- and post-drug treatment to identify mutations involved in the progression of resistance to the drugs rifampicin and isoniazid. in the rifampicin resistant strain, we confirmed a mutation in rpo ...201627156618
prevalence and transmission of pyrazinamide resistant mycobacterium tuberculosis in china.pyrazinamide (pza) is an important first-line anti-tuberculosis drug, however, there are relatively few available data on pza resistant (pza-r) rate in china. from june 2009 to june 2012, we selected 493 isolates from five field settings in china to investigate pza-r by pnca gene sequencing. the result showed that pza-r rate was 1.0% (2/196) among pan-susceptible isolates, 3.1% (4/130) among isoniazid (inh) mono-resistant isolates, 14.0% (6/43) among rifampin (rif) mono-resistant isolates and 43 ...201627156619
hiv-1 and the mycobacterium tuberculosis granuloma: a systematic review and meta-analysis.infection with hiv-1 greatly increases the risk of active tuberculosis (tb). although hypotheses suggest hiv-1 disrupts mycobacterium tuberculosis (mtb) granuloma function, few studies have examined this directly. the objective of this study was to determine what evidence exists about the effect hiv-1 co-infection has upon mtb granulomas. a systematic search of pubmed, web of science, and medline up to 20 march 2015 was conducted, to identify studies comparing mtb-infected tissue from hiv-1 infe ...201627156620
whole genome sequencing of mycobacterium tuberculosis for detection of recent transmission and tracing outbreaks: a systematic review.contact tracing complemented with genotyping is considered an important means of understanding person-to-person transmission of tuberculosis (tb). it still remains unclear whether whole genome sequencing (wgs) of mycobacterium tuberculosis can rule in transmission and how it performs in different human populations, risk groups and across tb lineages. this systematic review aimed to determine the sensitivity and specificity of wgs for detection of recent transmission using conventional epidemiolo ...201627156621
elevated serum 25-hydroxy (oh) vitamin d levels are associated with risk of tb progression in gambian adults.vitamin d is essential in the host defence against tuberculosis (tb) as an immune modulator. the aim of this study was to determine the level of 25-hydroxyvitamin d (25 (oh) d) from adult tb index cases before and after treatment and their exposed household contacts (hhc) in the gambia.201627156622
activity of nitazoxanide and tizoxanide against mycobacterium tuberculosis in vitro and in whole blood culture.nitazoxanide (ntz) and its metabolite tizoxanide (tiz) were studied as antimycobacterial agents in vitro (in mycobacterial growth indicator tube [mgit] cultures) and in a whole blood bactericidal assay. both ntz and tiz show high protein binding. in mgit cultures (albumin concentration = 78 μm), inhibition of mycobacterium tuberculosis growth occurred at total drug concentrations of ≥16 μg/ml, whereas in whole blood cultures (albumin concentration = 350 μm), ≥128 μg/ml was required. free drug fr ...201627156623
serial image analysis of mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary tb.faster elimination of drug tolerant 'persister' bacteria may shorten treatment of tuberculosis (tb) but no method exists to quantify persisters in clinical samples. we used automated image analysis to assess whether studying growth characteristics of individual mycobacterium tuberculosis colonies from sputum on solid media during early tb treatment facilitates 'persister' phenotyping. as time to detection (ttd) in liquid culture inversely correlates with total bacterial load we also evaluated th ...201627156626
molecular characterization of mycobacterium tuberculosis isolates from tanga, tanzania: first insight of miru-vntr and microarray-based spoligotyping in a high burden country.molecular typing of mycobacterium tuberculosis(mtb) has greatly enhanced the understanding of the population structure of mtb isolates and epidemiology of tuberculosis (tb). to characterize prevalent genotypes of mtb, microarrays‑based spoligotyping and mycobacterial interspersed repetitive unit‑variable number of tandem repeats (miru‑vntr) were applied on 80 isolates collected from primary health care facilities in tanga, north‑eastern tanzania. a total of 18 distinct spoligotypes were identifi ...201627156627
functional polymorphisms of the tlr7 and tlr8 genes contribute to mycobacterium tuberculosis infection.tuberculosis (tb) has recently re-emerged as a major global public health threat and mycobacterium tuberculosis (mtb) is a highly successful pathogen that evolved remarkable strategies to establish persistent infection. there is strong evidence that host genetic factors influence individual susceptibility to tb. in this study, we evaluated the associations between the tlr7 and tlr8 genetic polymorphisms and tb susceptibility in chinese individuals. the results demonstrated that the frequency of ...201627156628
strategies of genome editing in mycobacteria: achievements and challenges.tremendous amount of physiological and functional complexities acquired through decades of evolutionary pressure makes mycobacterium tuberculosis (mtb) one of the most dreadful microorganisms infecting humans from centuries. astonishing advances in genomics and genome editing tools substantially grew our knowledge about mtb as an organism but dramatically failed to completely understand it as a pathogen. though conventional tools based on homologous recombination, antisense, controlled proteolys ...201627156629
unraveling methylation changes of host macrophages in mycobacterium tuberculosis infection.to characterize at high resolution dna methylation changes of cytokines which occur in the genome of macrophages in association with mycobacterium tuberculosis (mtb) infection201627156630
the mechanism of cytoskeleton protein β-actin and cofilin-1 of macrophages infected by mycobacterium avium.cytoskeleton proteins and their regulation proteins could be influenced seriously in mycobacterium tuberculosis infection host cells leading to the apoptosis of host cells. macrophages infected by mycobacterium avium were detected from cell morphology and genome levels to analyze changes of the cytoskeleton of m. avium infection macrophages. then the expression of β-actin, cofilin-1 proteins in m. avium infected macrophages were analyzed by western blotting, and the apoptosis of m. avium infecti ...201627158391
protocol for a population-based molecular epidemiology study of tuberculosis transmission in a high hiv-burden setting: the botswana kopanyo study.mycobacterium tuberculosis (mtb) is transmitted from person to person via airborne droplet nuclei. at the community level, mtb transmission depends on the exposure venue, infectiousness of the tuberculosis (tb) index case and the susceptibility of the index case's social network. people living with hiv infection are at high risk of tb, yet the factors associated with tb transmission within communities with high rates of tb and hiv are largely undocumented. the primary aim of the kopanyo study is ...201627160840
antibiotic resistance mechanisms in m. tuberculosis: an update.treatment of tuberculosis (tb) has been a therapeutic challenge because of not only the naturally high resistance level of mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. currently standardized regimens require patients to daily ingest up to four drugs under direct observation of a healthcare worker for a period of 6-9 months. although they are quite effective in treating drug susceptible tb, these lengthy treatments often lead to p ...201627161440
methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens.adenoviruses represent the most widely used viral-vectored platform for vaccine design, showing a great potential in the fight against intracellular infectious diseases to which either there is a lack of effective vaccines or the traditional vaccination strategy is suboptimal. the extensive understanding of the molecular biology of adenoviruses has made the new technologies and reagents available to efficient generation of adenoviral-vectored vaccines for both preclinical and clinical evaluation ...201627162933
infantile osteoarticular tuberculosis misdiagnosed as bacillus calmette-guerin related osteomyelitis.tuberculosis, a re-emerging public health problem, is uncommon in infancy. two healthy completely immunized infants presenting with manifestations compatible with osteoarticular infection required surgical debridement. the cultures of the specimens were positive for m. tuberculosis (mtb) complex comprised multiple subspecies. one case was misdiagnosed as a bacillus calmette-guerin (bcg) related osteomyelitis by a polymerase chain reaction (pcr) based on detection of genes at the region of differ ...201527163076
characterization of the in vitro assembly of ftsz in arthrobacter strain a3 using light scattering.the self-assembly of ftsz, the bacterial homolog of tubulin, plays an essential role in cell division. light scattering technique is applied to real-time monitor the in vitro assembly of ftsz in arthrobacter strain a3, a newly isolated psychrotrophic bacterium. the critical concentration needed for the assembly is estimated as 6.7μm. the polymerization of ftsz in arthrobacter strain a3 requires both gtp and divalent metal ions, while salt is an unfavorable condition for the assembly. the ftsz po ...201627164494
a case of good's syndrome presenting with pulmonary tuberculosis.adult onset immunodeficiency associated with thymoma is a rare condition. the combination of hypogammaglobulinemia, reduced number of peripheral b and cd4+ t cells, along with thymoma constitutes good's syndrome (gs). this immunodeficiency condition is often complicated with opportunistic infection with organisms, like bacteria (haemophilus influenzae, streptococcus pneumonia etc), viruses (cytomegalovirus, herpes simplex etc), fungi and protozoa. we present an unusual case of good's syndrome wi ...201627164735
emerging tuberculosis pathogen hijacks social communication behavior in the group-living banded mongoose (mungos mungo).an emerging mycobacterium tuberculosis complex (mtc) pathogen, m. mungi, infects wild banded mongooses (mungos mungo) in northern botswana, causing significant mortality. this mtc pathogen did not appear to be transmitted through a primary aerosol or oral route. we utilized histopathology, spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats (miru-vntr), quantitative pcr (qpcr), and molecular markers (regions of difference [rds] from various mtc members, i ...201627165798
utility of mpt64 antigen test for differentiating mycobacteria: can correlation with liquid culture smear morphology add further value?clinical presentation of mycobacterium tuberculosis complex (mtbc) and non-tuberculous mycobacteria (ntm) infections may or may not be the same, but the treatment is always different. hence accurate differentiation between mtbc and ntm is of utmost importance.201727166037
the preprotein translocase yidc controls respiratory metabolism in mycobacterium tuberculosis.the yidc-oxa1-alb3 preprotein translocases play a vital role in membrane insertion of proteins in eukaryotes and bacteria. in a recent study we observed that rv3921c, which encodes putative yidc translocase in mycobacterium tuberculosis (mtb), is essential for in vitro growth of bacteria. however, the exact function of this particular protein remains to identify in mycobacterial pathogens. by performing a systematic study here we show that yidc of mtb is an envelope protein, which is required fo ...201627166092
practical approaches for mining frequent patterns in molecular datasets.pattern detection is an inherent task in the analysis and interpretation of complex and continuously accumulating biological data. numerous itemset mining algorithms have been developed in the last decade to efficiently detect specific pattern classes in data. although many of these have proven their value for addressing bioinformatics problems, several factors still slow down promising algorithms from gaining popularity in the life science community. many of these issues stem from the low user- ...201627168722
prevalence of pulmonary tuberculosis in young adult patients with type 1 diabetes mellitus in india.there is limited information on prevalence of pulmonary tuberculosis (ptb) in patients with type-1-diabetes. we assessed the prevalence of ptb in patients with type-1-diabetes attending the outpatient-clinic in a tertiary-care hospital.201627168934
rapid detection of rifampicin- and isoniazid-resistant mycobacterium tuberculosis using taqman allelic discrimination.multidrug-resistant tuberculosis (mdr-tb) is a global problem that many countries are challenged with. rapid and accurate detection of mdr-tb is critical for appropriate treatment and controlling of tb. the aim of the present study was to evaluate the taqman allelic discrimination without minor groove binder (mgb) as a rapid, efficient, and low-cost method for detection of drug resistant strains of mycobacterium tuberculosis.201627169012
synthesis and evaluation of the 2-aminothiazoles as anti-tubercular agents.the 2-aminothiazole series has anti-bacterial activity against the important global pathogen mycobacterium tuberculosis. we explored the nature of the activity by designing and synthesizing a large number of analogs and testing these for activity against m. tuberculosis, as well as eukaryotic cells. we determined that the c-2 position of the thiazole can accommodate a range of lipophilic substitutions, while both the c-4 position and the thiazole core are sensitive to change. the series has good ...201627171280
antibody detection tests for early diagnosis in tuberculous meningitis.tuberculous meningitis (tbm) is the most severe form of tuberculosis. microbiological confirmation is rare and treatment is often delayed. early diagnosis and immediate initiation of treatment are essential for effective tbm control. a systematic review was performed in this study to assess the diagnostic accuracy of detecting antibodies against mycobacterium tuberculosis in the cerebrospinal fluid (csf), according to standard methods. test performance was summarized using a bivariate random-eff ...201627173078
boosting bcg-primed responses with a subunit apa vaccine during the waning phase improves immunity and imparts protection against mycobacterium tuberculosis.heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. however, optimal timing to boost bcg-immunity using subunit vaccines remains unclear in clinical trials. here, we followed the adhesin apa-specific t-cell responses in bcg-primed mice and investigated its bcg-booster potential. the apa-specific t-cell response peaked 32-52 weeks after parenteral or mucosal bcg-priming but waned significantly by 78 weeks. a subunit-apa-boost during the contraction-pha ...201627173443
antimycobacterial triterpenes from the canadian medicinal plant sarracenia purpurea.the purple pitcher plant, sarracenia purpurea, is a medicinal plant used by the canadian first nations to treat a wide variety of illnesses. the mi'kmaq and wolastoqiyik (maliseet) peoples of eastern canada have traditionally used infusions of s. purpurea for the treatment of tuberculosis-like symptoms. previous investigations have shown methanolic extracts of s. purpurea to possess antimycobacterial activity.201627174081
draft genome sequence of branchiibius sp. ny16-3462-2, isolated from a mixed clinical sample.here, we report the release of a draft genome assembly of a gram-positive cocci branchiibius sp. ny16-3462-2 with a high-gc content, sequenced from a mixed clinical sample containing mycobacterium tuberculosis this genome is the first publicly available sequence from a representative of the genus branchiibius.201627174280
an automated approach for global identification of srna-encoding regions in rna-seq data from mycobacterium tuberculosis.deep-sequencing of bacterial transcriptomes using rna-seq technology has made it possible to identify small non-coding rnas, rna molecules which regulate gene expression in response to changing environments, on a genome-wide scale in an ever-increasing range of prokaryotes. however, a simple and reliable automated method for identifying srna candidates in these large datasets is lacking. here, after generating a transcriptome from an exponential phase culture of mycobacterium tuberculosis h37rv, ...201627174874
brucella melitensis and mycobacterium tuberculosis depict overlapping gene expression patterns induced in infected thp-1 macrophages.pathogens infecting mammalian cells have developed various strategies to suppress and evade their hosts' defensive mechanisms. in this line, the intracellular bacteria that are able to survive and propagate within their host cells must have developed strategies to avert their host's killing attitude. studying the interface of host-pathogen confrontation can provide valuable information for defining therapeutic approaches. brucellosis, caused by the brucella strains, is a zoonotic bacterial disea ...201527175205
[evaluation of the diagnostic performance of xpert mtb/rif test for the detection of mycobacterium tuberculosis and rifampin resistance in clinical samples].rapid and accurate detection of active tuberculosis (tb) cases is one of the most important goal of tuberculosis control programme. for this purpose, new methods are being developed to isolate, serotype and determine the drug resistance of the agent. xpert mtb/rif test (cepheidgenexpert® system, usa) that has been recently developed, is a real-time polymerase chain reaction-based method which detects mycobacterium tuberculosis complex and resistance of the strain to rifampicin (rif) from the cli ...201627175492
diagnostic potential of multi-targeted lamp (loop-mediated isothermal amplification) for osteoarticular tuberculosis.delay in diagnosing osteoarticular tuberculosis (oatb) contributes significantly to morbidity by causing disfiguration and neurological sequelae. the delay caused by conventional culture and the expertise and expense involved in other nucleic acid based tests, make lamp (loop-mediated isothermal amplification) assay a favorable middle path. we evaluated lamp assay using is6110 and mpb64 for rapid diagnosis of oatb by comparing with is6110 pcr and culture. lamp assay was performed on 140 synovial ...201727175946
prevalence and molecular characteristics of drug-resistant mycobacterium tuberculosis in beijing, china: 2006 versus 2012.as the epidemic of mdr-tb and xdr-tb becomes increasingly severe, it is important to determine the clinical characteristics and molecular epidemiology of mdr-tb and xdr-tb. recently, many studies have shown that clinical features and molecular characteristics of drug-resistant strains vary in different geographical areas, however, further information is needed to assess the dynamic evolution of drug-resistant tb. comparative studies between different time periods are necessary to elucidate the d ...201627176471
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
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
[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
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
infectiousness of hiv-seropositive patients with tuberculosis in a high-burden african setting.policy recommendations on contact investigation of hiv-seropositive patients with tuberculosis have changed several times. current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of hiv-seropositive and -seronegative index cases have been performed in sub-saharan africa.201627181053
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
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
detection of mycobacterium tuberculosis and mycobacterium bovis in sahiwal cattle from an organized farm using ante-mortem techniques.the aim of this study was to investigate the prevalence of bovine tuberculosis (tb) and detection of mycobacterium bovis in cattle from an organized dairy farm.201627182134
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
[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
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
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
[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
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
f420h2 is required for phthiocerol dimycocerosate synthesis in mycobacteria.phthiocerol dimycocerosates (pdim) are a group of cell surface-associated apolar lipids of mycobacterium tuberculosis and closely related mycobacteria, such as mycobacterium bovis and mycobacterium leprae a characteristic methoxy group of these lipids is generated from the methylation of a hydroxyl group of the direct precursors, the phthiotriols. the precursors arise from the reduction of phthiodiolones, the keto intermediates, by a ketoreductase. the putative phthiodiolone ketoreductase (pkr) ...201627185825
effect of experimental parameters on alginate/chitosan microparticles for bcg encapsulation.the aim of the present study was to develop novel mycobacterium bovis bacille calmette-guérin (bcg)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against mycobacterium tuberculosis by the intranasal route. bcg was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. for comp ...201627187418
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
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
therapeutic effect of recombinant mutated interleukin 11 in the mouse model of tuberculosis.earlier we demonstrated that blocking of interleukin 11 (il-11) by systemic administration of anti-il-11 antibodies attenuates severity of mycobacterium tuberculosis infection in mice. the substitution w147a in the il-11 molecule creates the form of cytokine capable to disrupt gp130/il11r signaling complex formation, thus serving as a high-affinity specific antagonist of il-11-mediated signaling. we hypothesized that this mutant form of il-11 may serve as an effective tool for inhibition of nati ...201627190186
antigenic characterization of dimorphic surface protein in mycobacterium tuberculosis.the mycobacterium tuberculosis rv0679c protein is a surface protein that contributes to host cell invasion. we previously showed that a single nucleotide transition of the rv0679c gene leads to a single amino acid substitution from asparagine to lysine at codon 142 in the beijing genotype family. in this study, we examined the immunological effect of this substitution. several recombinant proteins were expressed in escherichia coli and mycobacterium smegmatis and characterized with antisera and ...201627190237
next-generation sequencing of mycobacterium tuberculosis. 201627191040
targeting the motion of shikimate kinase: development of competitive inhibitors that stabilize an inactive open conformation of the enzyme.the large conformational changes observed by molecular dynamics simulation studies on the product release in the lid and shikimic acid binding (sb) domains of the shikimate kinase (sk) enzyme have been exploited in the development of reversible competitive inhibitors against sk from mycobacterium tuberculosis and helicobacter pylori. this enzyme is a recognized target for antibiotic drug discovery. the reported c5-substituted shikimic acid analogues interact with the dynamic apolar pocket that s ...201627191386
identification of a transcription factor that regulates host cell exit and virulence of mycobacterium tuberculosis.the interaction of mycobacterium tuberculosis (mtb) with host cell death signaling pathways is characterized by an initial anti-apoptotic phase followed by a pro-necrotic phase to allow for host cell exit of the bacteria. the bacterial modulators regulating necrosis induction are poorly understood. here we describe the identification of a transcriptional repressor, rv3167c responsible for regulating the escape of mtb from the phagosome. increased cytosolic localization of mtbδrv3167c was accompa ...201627191591
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
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
host immune responses differ between m. africanum- and m. tuberculosis-infected patients following standard anti-tuberculosis treatment.epidemiological differences exist between mycobacterium africanum (maf)- and mycobacterium tuberculosis (mtb)-infected patients, but to date, contributing host factors have not been characterised. we analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and esat6/cfp-10-, whole-maf- and mtb-stimulated blood samples of 26 maf- and 49 mtb-hiv-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. before treatment ...201627192147
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
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