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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
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
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
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
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
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
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
distribution and association of mycobacterium tuberculosis cas lineage with multidrug resistance in north india.a tertiary care hospital in north india.201627155185
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
indole-2-carboxamide-based mmpl3 inhibitors show exceptional antitubercular activity in an animal model of tuberculosis infection.our team had previously identified certain indolecarboxamides that represented a new chemical scaffold that showed promising anti-tb activity at both an in vitro and in vivo level. based on mutational analysis using bacteria found resistant to one of these indolecarboxamides, we identified the trehalose monomycolate transporter mmpl3 as the likely target of these compounds. in the present work, we now further elaborate on the sar of these compounds, which has led in turn to the identification of ...201627275668
use of genexpert mycobacterium tuberculosis/rifampicin for rapid detection of rifampicin resistant mycobacterium tuberculosis strains of clinically suspected multi-drug resistance tuberculosis cases.multi-drug resistance (mdr) tb is defined as tuberculosis (tb) disease caused by a strain of mycobacterium tuberculosis (mtb) that was resistant to at least isoniazid and rifampicin (rif). emerging multidrug-resistant tb is one of the major concerns of health policy and rapid detection of m. tuberculosis and detection of rif resistance in infected patients are essential for disease management. the aim of this study was to evaluate patterns of rif resistance in cases of sputum positive pulmonary ...201627275481
a retrospective review of the two-step tuberculin skin test in dialysis patients.reactivation of latent mycobacterium tuberculosis infection (ltbi) is a health concern for patients on dialysis or receiving a kidney transplant, as these patients are often immunosuppressed. the most frequently used test for ltbi screening in this population is the tuberculin skin test (tst). the diagnostic accuracy (sensitivity and specificity) of the tst in a contemporary north american or western european dialysis population is unknown.201627274397
nonclassical mhc ib-restricted cd8+ t cells recognize mycobacterium tuberculosis-derived protein antigens and contribute to protection against infection.mhc ib-restricted cd8+ t cells have been implicated in host defense against mycobacterium tuberculosis (mtb) infection. however, the relative contribution of various mhc ib-restricted t cell populations to anti-mycobacterial immunity remains elusive. in this study, we used mice that lack mhc ia (kb-/-db-/-), mhc ia/h2-m3 (kb-/-db-/-m3-/-), or β2m (β2m-/-) to study the role of m3-restricted and other mhc ib-restricted t cells in immunity against mtb. unlike their dominant role in listeria infecti ...201627272249
a rare case of pott's disease (spinal tuberculosis) mimicking metastatic disease in the southern region of denmark.pott's disease (pd) or spinal tuberculosis is a rare condition which accounts for less than 1% of total tuberculosis (tb) cases. the incidence of pd has recently increased in europe and the united states, mainly due to immigration; however, it is still a rare diagnosis in scandinavian countries, and if overlooked it might lead to significant neurologic complications.201627272065
molecular analysis of genetic mutations among cross-resistant second-line injectable drugs reveals a new resistant mutation in mycobacterium tuberculosis.mutations causing mono and cross-resistance among amikacin, kanamycin and capreomycin of second-line injectable drugs (slids) namely are not well understood. we investigated 124 isolates of mycobacterium tuberculosis for mutations within rrs, eis, tlya and efflux pump (rv1258c and rv0194) genes involved in resistance towards slids. the distribution of mutations across these genes were significantly different in strains with mono-resistance or cross-resistance. a new mutation g878a was found in r ...201627298046
role of gyrb mutations in pre-extensively and extensively drug-resistant tuberculosis in thai clinical isolates.dna gyrase mutations are a major cause of quinolone resistance in mycobacterium tuberculosis we therefore conducted the first comprehensive study to determine the diversity of gyrase mutations in pre-extensively drug-resistant (pre-xdr) (n = 71) and extensively drug-resistant (xdr) (n = 30) thai clinical tuberculosis (tb) isolates. all pre-xdr-tb and xdr-tb isolates carried at least one mutation within the quinolone resistance-determining region of gyra (g88a [1.1%], a90v [17.4%], s91p [1.1%], o ...201627297489
therapeutic potential of the mycobacterium tuberculosis mycolic acid transporter, mmpl3.in recent years, whole-cell-based screens for novel small molecule inhibitors active against mycobacterium tuberculosis in culture followed by the whole-genome sequencing of spontaneous resistant mutants have identified multiple chemical scaffolds thought to kill the bacterium through the inactivation of the mycolic acid transporter, mmpl3. consistent with the fact that mmpl3 is required for the formation of the mycobacterial outer membrane, we have conclusively shown in this study, using condit ...201627297488
a subset of protective γ9δ2 t cells is activated by novel mycobacterial glycolipid components.γ9δ2 t cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (tb) infection and bacillus calmette guérin (bcg) vaccination. mycobacterium-expanded γ9δ2 t cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [ipp] and (e)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [hmbpp]}-responsive γ9δ2 t cells, expressing an oligoclonal set of t cell r ...201627297390
mir-381-3p regulates the antigen-presenting capability of dendritic cells and represses antituberculosis cellular immune responses by targeting cd1c.tuberculosis is still the widest spread infectious disease in the world, and more in-depth studies are needed on the interaction between the pathogen and the host. due to the highest lipid components in mycobacterium tuberculosis, the cd1 family that specifically presents antigenic lipids plays important roles in the antituberculosis immunity, especially cd1c, which functions as the intracellular ag inspector at the full intracellular range. however, downregulation of the cd1c mrna level has bee ...201627296666
[tuberculosis: actual problems with diagnosis and treatment].tuberculosis (tb) is an infectious disease caused by mycobacterium tuberculosis complex. it remains health problem also in developed countries. most common form of tuberculosis is pulmonary disease but other sites of the body can be affected (extrapulmonary tb). as tb incidence falls, the probability of developing active diseases in people infected with m. tuberculosis is higher among imunocompromised people and in people from risk groups. people who present with unexplained cough lasting two or ...201627421129
ru(ii)/clotrimazole/diphenylphosphine/bipyridine complexes: interaction with dna, bsa and biological potential against tumor cell lines and mycobacterium tuberculosis.three ruthenium complexes [rucl(ctz)(bipy)(p-p)]pf6 [p-p=1,2-bis(diphenylphosphino)ethane (dppe-1), 1,4-bis(diphenylphosphino)butane (dppb-2) and 1,1'-bis(diphenylphosphino)ferrocene (dppf-3), bipy=2,2'-bipiridine and clotrimazole (ctz) 1-[(2-chlorophenyl)diphenylmethyl]-1h-imidazole] were synthesized. these complexes were characterized by a combination of elemental analysis, molar conductivity, infrared and uv-vis spectroscopy, (1)h, (13)c{(1)h} and (31)p{(1)h} nuclear magnetic resonance techni ...201627383651
[evaluation of discriminatory power of molecular epidemiology techniques in mycobacterium tuberculosis venezuelan isolates].the techniques of spoligotyping and mycobacterial interspersed repetitive unit and variable-number tandem repeat typing with 24 loci (miru-vntr-24), have been used to study the molecular epidemiology of tuberculosis. the aim of this study was: to evaluate the discriminative power of miru-vntr 24 loci alone and in association with spoligotyping in clinical isolates of m tuberculosis in venezuela; the allelic diversity of the 24 loci; and the discriminative power for the combination of 24 and 15 l ...201627382799
identification of quantitative proteomic differences between mycobacterium tuberculosis lineages with altered virulence.evidence currently suggests that as a species mycobacterium tuberculosis exhibits very little genomic sequence diversity. despite limited genetic variability, members of the m. tuberculosis complex (mtbc) have been shown to exhibit vast discrepancies in phenotypic presentation in terms of virulence, elicited immune response and transmissibility. here, we used qualitative and quantitative mass spectrometry tools to investigate the proteomes of seven clinically-relevant mycobacterial strains-four ...201627303394
fidelity and promiscuity of a mycobacterial glycosyltransferase.members of the genus mycobacterium cause devastating human diseases, including tuberculosis. mycobacterium tuberculosis can resist some antibiotics because of its durable and impermeable cell envelope. this barrier is assembled from saccharide building blocks not found in mammals, including galactofuranose (galf). within the cell envelope, galf residues are linked together to afford an essential polysaccharide, termed the galactan. the formation of this polymer is catalyzed by the glycosyltransf ...201627302377
intracardiac tuberculomas caused by mycobacterium tuberculosis in a dog.this paper presents an unusual form of disseminated mycobacterium tuberculosis infection in a dog. the infection lasted at least one year and its main gross lesions were massive cardiac tuberculomas. to the best of our knowledge, this is the first report of heart tuberculomas in a dog.201627301275
evaluation of the inhibitory activity of (aza)isoindolinone-type compounds: toward in vitro inha action, mycobacterium tuberculosis growth and mycolic acid biosynthesis.inhibitors of the mycobacterium tuberculosis enoyl-acp reductase (inha) are considered as potential promising therapeutics for the treatment of tuberculosis. previously, we reported that azaisoindolinone-type compounds displayed, in vitro, inhibitory activity toward inha. herein, we describe chemical modifications of azaisoindolinone scaffold, the synthesis of 15 new compounds and their evaluations toward the in vitro inha activity. based on these results, a structure-inha inhibitory activity re ...201627301022
application of the multistate tuberculosis pharmacometric model in patients with rifampicin-treated pulmonary tuberculosis.this is the first clinical implementation of the multistate tuberculosis pharmacometric (mtp) model describing fast-, slow-, and nonmultiplying bacterial states of mycobacterium tuberculosis. colony forming unit data from 19 patients treated with rifampicin were analyzed. a previously developed rifampicin population pharmacokinetic (pk) model was linked to the mtp model previously developed using in vitro data. drug effect was implemented as exposure-response relationships tested at several effe ...201627299939
early detection of multidrug resistant (mdr) mycobacterium tuberculosis in a single tube with in-house designed fluorescence resonance energy transfer (fret) probes using real-time pcr.rapid and correct diagnosis is crucial for the management of multidrug resistance (mdr) in mycobacterium tuberculosis (mtb). the present study aims at rapid diagnosis for identification of multidrug resistance tuberculosis (mdr-tb) using real-time pcr. fret hybridization probes targeting most prominent four selected codons for rpob526 and 531 and for katg314 and 315 genes were designed and evaluated on 143 clinical mtb isolates and paired sputa for rapid detection of mdr-tb. the results of real- ...201627295919
cytotoxic labdane diterpenes from hedychium ellipticum buch.-ham. ex sm.in order to reveal the constituents and their biological activities, we carried out a phytochemical study on hedychium ellipticum buch.-ham. ex sm. (zingiberaceae). ten labdane diterpenoids (1-10) were isolated from the rhizomes of h. ellipticum for the first time. their structures were identified on the basis of spectroscopic analyses including two-dimensional nmr and comparison with literature data. all of these compounds were evaluated for their antimycobacterial activity against mycobacteriu ...201627294893
zoonotic tuberculosis. a comprehensive one health approach.the objective of this report is to provide information on mycobacterium tuberculosis complex infections in animals and in humans. included is information on the susceptibility of different species as well as information on etiology, epidemiology, pathogenesis, diagnosis, prevention and control of this disease. the term one health has been adopted to describe the unified human medical and veterinary interdisciplinary/multidisciplinary collaborative approach to zoonoses and will be critical for fu ...201627295705
twenty years of mycobacterial glycans: furanosides and beyond.the cell surface (or cell wall) of bacteria is coated with carbohydrate (or glycan) structures that play a number of important roles. these include providing structural integrity, serving as a permeability barrier to extracellular compounds (e.g., drugs) and modulating the immune system of the host. of interest to this account is the cell wall structure of mycobacteria. there are a host of different mycobacterial species, some of which cause human disease. the most well-known is mycobacterium tu ...201627294709
mycobacterial l-forms are found in cord blood: a potential vertical transmission of bcg from vaccinated mothers.our previous studies showed that mycobacterial l-forms persist in the blood of bcg vaccinated people and that bcg vaccine is able to produce, under appropriate conditions, filterable, self-replicating l-bodies with virus-like size. because filterability is one of the characteristics of l-forms, considerable interest has been shown in their capacity to cross the maternal-fetal barrier. the current study demonstrated isolation of mycobacterial l-form cultures from umbilical cord blood of 5 healthy ...201627294392
mycobacterium tuberculosis contaminant risk on bone marrow aspiration material from iliac bone patients with active tuberculous spondylitis.there was a concern on mycobacterium tuberculosis spreading to the bone marrow, when it was applied on tuberculous spine infection. this research aimed to study the probability of using autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis. as many as nine patients with tuberculous spondylitis were used as samples. during the procedure, the vertebral lesion material and iliac bone marrow aspirates were obtained for acid fast staining, bacteria cult ...201627294117
structural views along the mycobacterium tuberculosis mend reaction pathway illuminate key aspects of thiamin diphosphate-dependent enzyme mechanisms.menaquinone (mq) is an essential component of the respiratory chains of many pathogenic organisms, including mycobacterium tuberculosis (mtb). the first committed step in mq biosynthesis is catalyzed by 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase (mend), a thiamin diphosphate (thdp)-dependent enzyme. catalysis proceeds through two covalent intermediates as the substrates 2-oxoglutarate and isochorismate are successively added to the cofactor before final cleavage o ...201627291649
cheminformatics based machine learning approaches for assessing glycolytic pathway antagonists of mycobacterium tuberculosis.tuberculosis is the second leading cause of death from an infectious disease worldwide after hiv, thus reasoning the expeditions in antituberculosis research. the rising number of cases of infection by resistant forms of m. tuberculosis has given impetus to the development of novel drugs that have different targets and mechanisms of action against the bacterium.201627291589
complement 3 receptor expression in individuals with type 2 diabetes.according to the world health organization, as of 2014 9% of the world's adult population is affected by diabetes. uncontrolled diabetes is a pro-inflammatory process that increases generation of reactive oxygen species (ros).201627291248
microrna-206 regulates the secretion of inflammatory cytokines and mmp9 expression by targeting timp3 in mycobacterium tuberculosis-infected thp-1 human macrophages.tuberculosis (tb) is a serious disease that is characterized by mycobacterium tuberculosis (m.tb)-triggered immune system impairment and lung tissue damage shows limited treatment options. micrornas (mirnas) are regulators of gene expression that play critical roles in many human diseases, and can be up- or downregulated by m.tb infection in macrophage. recently, tissue inhibitor of matrix metalloproteinase (timp) 3 has been found to play roles in regulating macrophage inflammation. here, we fou ...201627291149
[determination of in vitro synergy by a checkerboard method when 3 core antimicrobial agents of the retreatment new scheme combined against mdr-mtb and xdr-mtb].in order to detect the in vitro synergistic effect of 4 drugs-pasiniazid (pa), moxifloxacin, rifabutin and rifapentini on multidrug-resistant mycobacterium tuberculosis (mdr-mtb) and extensively drug-resistant mycobacterium tuberculosis(xdr-mtb), which were core drugs of"the program of retreatment research of tuberculosis".201627289577
reassessment of the positive predictive value and specificity of xpert mtb/rif: a diagnostic accuracy study in the context of community-wide screening for tuberculosis.community-wide screening for tuberculosis with xpert mtb/rif as a primary screening tool overcomes some of the limitations of conventional screening. however, concerns exist about the low positive predictive value of this test in screening settings. we did a cross-sectional assessment of this diagnostic test to directly estimate the actual positive predictive value of xpert mtb/rif when used in the setting of community-wide screening for tuberculosis, and to draw an inference about the specifici ...201627289387
identification of novel 2-aminothiazole conjugated nitrofuran as antitubercular and antibacterial agents.the emergence of antibiotic resistant pathogens is an ongoing main problem in the therapy of bacterial infections. in order to develop promising antitubercular and antibacterial lead compounds, we designed and synthesized a new series of derivatives of 2-aminothiazole conjugated nitrofuran with activities against both mycobacterium tuberculosis and staphylococcus aureus. eight compounds 12e, 12k, 12l, 12m, 18a, 18d, 18e, and 18j emerged as promising antitubercular agents. structure-activity rela ...201627289321
identification of mycobacterium tuberculosis enzyme involved in vitamin d and 7-dehydrocholesterol metabolism.problems arising during treatment of tuberculosis are well known, therefore studies of mycobacterium drug molecular targets are an area of particular importance. members of the cytochrome p450 family (cyp) may belong to potential candidates for drug targets being involved in metabolism of biologically important molecules in the host organism. cyp124 of mycobacterium tuberculosis (mtcyp124) catalyzes ω-hydroxylation of methyl-branched lipids. the data obtained in the present study indicate that t ...201627289046
quantification of colony-forming units for m. tuberculosis complex using gyrb-based real-time pcr assay.it is inappropriate to select insertion sequence (is) 6110 as the amplification target for the quantitative analysis of mycobacterium tuberculosis complex (mtc).201627287652
diagnostic accuracy of a uniform research case definition for tbm in children: a prospective study.bacteriological confirmation of tuberculous meningitis (tbm) is problematic, and rarely guides initial clinical management. a uniform tbm case definition has been proposed for research purposes.201627287642
a survey of tuberculosis infection control practices at the nih/niaid/daids-supported clinical trial sites in low and middle income countries.health care associated transmission of mycobacterium tuberculosis (tb) is well described. a previous survey of infection control (ic) practices at clinical research sites in low and middle income countries (lmic) funded by the national institute of allergy and infectious diseases (niaid) conducting hiv research identified issues with respiratory ic practices. a guideline for tb ic based on international recommendations was developed and promulgated. this paper reports on adherence to the guideli ...201627287374
spirooxindoles as novel 3d-fragment scaffolds: synthesis and screening against cyp121 from m. tuberculosis.the search for new scaffolds to complement current hts and fragment libraries is an active area of research. the development of novel strategies to synthesise compounds with 3d character in order to expand the diversity of a fragment library was explored. a range of substituted bicyclo[2,2,1]spirooxindoles were synthesised using a diels-alder [4+2] cycloaddition reaction. both diastereoisomers were isolated from the reactions and these 3d fragment scaffolds were screened against the cytochrome p ...201627287372
variation in c - reactive protein response according to host and mycobacterial characteristics in active tuberculosis.the c - reactive protein (crp) response is often measured in patients with active tuberculosis (tb) yet little is known about its relationship to clinical features in tb, or whether responses differ between ethnic groups or with different mycobacterium tuberculosis (m.tb) strain types. we report the relationship between baseline serum crp prior to treatment and disease characteristics in a metropolitan population with tb resident in a low tb incidence region.201627287260
predictive modeling targets thymidylate synthase thyx in mycobacterium tuberculosis.there is an urgent need to identify new treatments for tuberculosis (tb), a major infectious disease caused by mycobacterium tuberculosis (mtb), which results in 1.5 million deaths each year. we have targeted two essential enzymes in this organism that are promising for antibacterial therapy and reported to be inhibited by naphthoquinones. thyx is an essential thymidylate synthase that is mechanistically and structurally unrelated to the human enzyme. dna gyrase is a dna topoisomerase present in ...201627283217
iron acquisition pathways as targets for antitubercular drugs.tuberculosis nowadays ranks as the second leading cause of death from an infectious disease worldwide. in the last twenty years, this disease has again started to spread mainly for the appearance of multi-drug resistant forms. therefore, new targets are needed to address the growing emergence of bacterial resistance and for antitubercular drug development. efficient iron acquisition is crucial for the pathogenesis of mycobacterium tuberculosis, because it serves as cofactor in many essential bio ...201627281295
ag85a/esat-6 chimeric dna vaccine induces an adverse response in tuberculosis-infected mice.the mycobacterium tuberculosis (m. tb) antigens encoded by the 6 kda early secretory antigenic target (esat-6) and antigen 85a (ag85a) genes are known to exert protective effects against tuberculosis in animal models. in addition, these antigens represent vaccine components that were tested in early human clinical trials. in the present study, a chimeric dna vaccine was constructed that contained two copies of the esat‑6 gene inserted into the ag85a gene from m. tb. balb/c mice were treated with ...201627279275
syndecans promote mycobacterial internalization by lung epithelial cells.pulmonary tuberculosis (tb) is an airborne disease caused by the intracellular bacterial pathogen mycobacterium tuberculosis (mtb). alveolar epithelial cells and macrophages are the first point of contact for mtb in the respiratory tract. however, the mechanisms of mycobacterial attachment to, and internalization by, nonprofessional phagocytes, such as epithelial cells, remain incompletely understood. we identified syndecan 4 (sdc4) as mycobacterial attachment receptor on alveolar epithelial cel ...201627279134
high-resolution melting analysis for molecular detection of multidrug resistance tuberculosis in peruvian isolates.the emergence of multidrug-resistant strains is a major health problem especially for countries with high tb incidence such as peru. in this study, we evaluated high resolution melting (hrm) assay in peruvian isolates for the detection of mutations within rpob, katg genes and promoter region inha to determine isoniazid and rifampicin resistance in mycobacterium tuberculosis (mtb).201627278526
working conditions and tuberculosis mortality in england and wales, 1890-1912: a retrospective analysis of routinely collected data.modelling studies suggest that workplaces may be important sites of mycobacterium tuberculosis transmission in high burden countries today. contemporary data on tuberculosis by occupation from these settings are scarce. however, historical data on tuberculosis risk in different occupations are available and may provide insight into workplace transmission. we aimed to ascertain whether, in a high burden setting, individuals working in crowded indoor environments (exposed) had greater tuberculosis ...201627207086
design, synthesis and biological evaluation of novel quinoline-based carboxylic hydrazides as anti-tubercular agents.in this study, seventeen novel quinoline-based carboxylic hydrazides were designed as potential anti-tubercular agents using molecular hybridization approach and evaluated in-silico for drug-likeness behavior. the compounds were synthesized, purified, and characterized using spectral techniques (like ftir, (1) h nmr, and mass). the in-vitro anti-tubercular activity (against mycobacterium tuberculosish37ra) and cytotoxicity against human lung fibroblast cells were studied. among the tested hydraz ...201627203404
role of alanine dehydrogenase of mycobacterium tuberculosis during recovery from hypoxic nonreplicating persistence.mycobacterium tuberculosis can maintain a nonreplicating persistent state in the host for decades, but must maintain the ability to efficiently reactivate and produce active disease to survive and spread in a population. among the enzymes expressed during this dormancy is alanine dehydrogenase, which converts pyruvate to alanine, and glyoxylate to glycine concurrent with the oxidation of nadh to nad. it is involved in the metabolic remodeling of m. tuberculosis through its possible interactions ...201627203084
modular organization of the esx-5 secretion system in mycobacterium tuberculosis.mycobacteria utilize type vii secretion systems (t7ss) to export many of their important virulence proteins. the t7ss encompasses five homologous secretion systems (esx-1 to esx-5). most pathogenic mycobacterial species, including the human pathogen mycobacterium tuberculosis, possess all five esx systems. the esx-1, -3, and -5 systems are important for virulence of mycobacteria but the molecular mechanisms of their secretion apparatus and the identity and activity of secreted effector proteins ...201627200304
multi-fluorescence real-time pcr assay for detection of rif and inh resistance of m. tuberculosis.failure to early detect multidrug-resistant tuberculosis (mdr-tb) results in treatment failure and poor clinical outcomes, and highlights the need to rapidly detect resistance to rifampicin (rif) and isoniazid (inh).201627199947
scenario analysis for programmatic tuberculosis control in western province, papua new guinea.tuberculosis (tb) and multidrug-resistant tb (mdr-tb) are major health problems in western province, papua new guinea. while comprehensive expansion of tb control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. we parameterized our previously described mathematical model of mycobacterium tuberculosis dynamics in western province, following an epidemiologic assessment. five hypothetical scenarios representing a ...201627199387
complete genome sequence of mycobacterium tuberculosis clinical isolate spoligotype sit745/eai1-mys.mycobacterium tuberculosis is known to cause pulmonary and extrapulmonary tuberculosis. this organism showed special phylogeographical specificity. here, we report the complete genome sequence of m. tuberculosis clinical isolate spoligotype sit745/eai1-mys, which was isolated from a malaysian tuberculosis patient.201627198011
functional characterization of pyrg, an unusual nonribosomal peptide synthetase module from the pyridomycin biosynthetic pathway.pyridomycin is an antimycobacterial cyclodepsipeptide assembled by a nonribosomal peptide synthetase/polyketide synthase hybrid system. analysis of its cluster revealed a nonribosomal peptide synthetase (nrps) module, pyrg, that contains two tandem adenylation domains and a pks-type ketoreductase domain. in this study, we biochemically validated that the second a domain recognizes and activates α-keto-β-methylvaleric acid (2-kvc) as the native substrate; the first a domain was not functional but ...201627197800
capillary electrophoresis as a method to determine underivatized urinary lipoarabinomannans, a biomarker of active tuberculosis caused by mycobacterium tuberculosis.tuberculosis is a devastating contagious disease caused by mycobacterium tuberculosis. this is the first report describing the development of novel capillary electrophoresis methods to detect lipoarabinomannans shed into the blood circulation by replicating bacteria. the novelty of the methods is the detection without derivatization. the lipoarabinomannan is detected owing to the ionization of the diverse functional groups of the structure, such as the multibranched mannan domain or the phosphat ...201627196985
in vitro activity of copper(ii) complexes, loaded or unloaded into a nanostructured lipid system, against mycobacterium tuberculosis.tuberculosis (tb) is an infectious disease caused mainly by the bacillus mycobacterium tuberculosis (mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. the aim of this study was to evaluate a nanostructured lipid system (nls) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and eumulgin(®) hre 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer ph = 7.4) as a tactic to ...201627196901
[preclinical and clinical trials of the new tuberculosis drug perchlozon].the paper sets forth the stages of design and introduction of the new russian tuberculosis (tb) drug perchlozon registered in the russian federation in 2012. based on the results of phases i-iii clinical trials, the authors evaluate the efficacy and safety of the agent and consider the adverse effects of its treatment for respiratory tb. the use of perchlozon as a component of combination therapy versus standard chemotherapy regimens significantly reduces abacillation time in pulmonary tb caused ...201627195324
evaluation of the effect of pulicaria gnaphalodes and perovskia abrotanoides essential oil extracts against mycobacterium tuberculosis strains.mycobacterium tuberculosis (mtb) is the causative agent of tuberculosis (tb), which remains one of the major public health problems in the world. the increasing incidence of multidrug-resistant tuberculosis (mdr-tb) and extensively drug-resistant tuberculosis (xdr-tb) worldwide highlights the urgent need to search for alternative antimycobacterial agents. more and more people in developing countries utilize traditional medicine for their major primary health care needs. it has been determined th ...201627195252
interleukin-10 family and tuberculosis: an old story renewed.the interleukin-10 (il-10) family of cytokines consists of six immune mediators, namely il-10, il-19, il-20, il-22, il-24 and il-26. il-10, il-22, il-24 and il-26 are critical for the regulation of host defense against mycobacterium tuberculosis infections. specifically, il-10 and il-26 can suppress the antimycobacterial immunity and promote the survival of pathogen, while il-22 and il-24 can generate protective responses and inhibit the intracellular growth of pathogen. knowledge about the new ...201627194948
the emergence of latent infection in the early evolution of mycobacterium tuberculosis.mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. from the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a détente with the host immune response. however, a small fraction of latent infections reactivate to the disease state. thus, latency has been argued to provide a safe harbour for future infections ...201627194699
standard genotyping overestimates transmission of mycobacterium tuberculosis among immigrants in a low-incidence country.immigrants from regions with a high incidence of tuberculosis (tb) are a risk group for tb in low-incidence countries such as switzerland. in a previous analysis of a nationwide collection of 520 mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat [miru-vntr] typing and spoligotyping). here, we used whole-genome sequencing (wgs) to re ...201627194683
triclosan-induced genes rv1686c-rv1687c and rv3161c are not involved in triclosan resistance in mycobacterium tuberculosis.a key issue towards developing new chemotherapeutic approaches to fight mycobacterium tuberculosis is to understand the mechanisms underlying drug resistance. previous studies have shown that genes rv1686c-rv1687c and rv3161c, predicted to encode an atp-binding cassette transporter and a dioxygenase respectively, are induced in the presence of triclosan and other antimicrobial compounds. therefore a possible role in drug resistance has been suggested for the products of these genes although no f ...201627193696
anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of melophlus sp.tuberculosis (tb), caused by mycobacterium tuberculosis infection, is a major world health problem that is responsible for the deaths of 1.5 million people each year. in addition, the requirement for long-term therapy to cure tb complicates treatment of the disease. one of the major reasons for the extended chemotherapeutic regimens and wide epidemicity of tb is that m. tuberculosis has the ability to persist in a dormant state. we therefore established a new screening system to search for subst ...201627193014
molecular characterization of mycobacterium tuberculosis isolates from tehran, iran by restriction fragment length polymorphism analysis and spoligotyping.introduction characterization of mycobacterium tuberculosis (mtb) isolates by dna fingerprinting has contributed to tuberculosis (tb) control. the aim of this study was to determine the genetic diversity of mtb isolates from tehran province in iran. methods mtb isolates from 60 iranian and 10 afghan tb patients were fingerprinted by standard is6110-restriction fragment length polymorphism (rflp) analysis and spoligotyping. results the copy number of is6110 ranged from 10-24 per isolate. the isol ...201627192590
total synthesis of teixobactin.the first total synthesis of the cyclic depsipeptide natural product teixobactin is described. synthesis was achieved by solid-phase peptide synthesis, incorporating the unusual l-allo-enduracididine as a suitably protected synthetic cassette and employing a key on-resin esterification and solution-phase macrolactamization. the synthetic natural product was shown to possess potent antibacterial activity against a range of gram-positive pathogenic bacteria, including a virulent strain of mycobact ...201627191730
3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamides bearing hydrophobic substituents at the 7-position of the benzodioxane nucleus potently inhibit methicillin-resistant sa and mtb cell division.lipophilic substituents at benzodioxane c (7) of 3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamide improve the antibacterial activity against methicillin-resistant staphylococcus aureus strains to mic values in the range of 0.2-2.5 μg/ml, whereas hydrophilic substituents at the same position and modifications at the benzodioxane substructure, excepting for replacement with 2-cromanyl, are deleterious. some of the lead compounds also exhibit good activity against mtb. parallel sars to those of 3- ...201627191617
next-generation sequencing of mycobacterium tuberculosis. 201627191040
structure-based epitope mapping of mycobacterium tuberculosis secretary antigen mtc28.secretary proteins of mycobacterium tuberculosis are key players of the mycobacterial infection pathway. mtc28 is a 28-kda proline-rich secretary antigen of mycobacterium tuberculosis and is only conserved in pathogenic strains of mycobacteria. here we report the crystal structure of mtc28 at 2.8- and 2.15-å resolutions for the structure-based epitope design. mtc28 shares a "mog1p"-fold consisting of seven antiparallel β strands stacked between α helices. five probable epitopes have been located ...201627189947
bacillus calmette-guérin-inoculation at different time points influences the outcome of c57bl/6 mice infected with plasmodium chabaudi chabaudi as.bacillus calmette-guérin (bcg) is an attenuated mycobacterium tuberculosis vaccine. we performed a series of co-infection experiments with bcg-plasmodium chabaudi chabaudi landau, 1965 as using c57bl/6 mice to analyse whether bcg can affect the development of protective immunity to infection with plasmodium spp. and the mechanism of this protection. we divided mice into four groups: bcg-inoculation 4 weeks prior to p. c. chabaudi as infection (b-4w-pc); simultaneous bcg-inoculation and p. c. cha ...201627188912
mutations in pepq confer low-level resistance to bedaquiline and clofazimine in mycobacterium tuberculosis.the novel atp synthase inhibitor bedaquiline recently received accelerated approval for treatment of multidrug-resistant tuberculosis and is currently being studied as a component of novel treatment-shortening regimens for drug-susceptible and multidrug-resistant tuberculosis. in a limited number of bedaquiline-treated patients reported to date, ≥4-fold upward shifts in bedaquiline mic during treatment have been attributed to non-target-based mutations in rv0678 that putatively increase bedaquil ...201627185800
[eales' disease].the syndrome of recurrent vitreous hemorrhages in young men was described for the first time by henry eales in 1880. the association with a clinical manifestation of ocular inflammation was reported 5years later. eales disease affects young adults who present with ischemic retinal vasculitis, with the peripheral retina most commonly affected. most cases have been reported in south asia. although the etiology of this abnormality is unknown, it may be related to an immune sensitivity to mycobacter ...201627185661
synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine-3-carboxamides.a series of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine carboxamides 7a-s were designed and synthesized. the required building block, 2-dibenzo[b,d]thiophenyl imidazo[1,2-a]pyridine carboxylic acid (5) was synthesized from commercial dibenzo[b,d]thiophene in good yields following five-step reaction sequence. the desired carboxamides 7a-s was prepared through coupling of acid 5 with various benzyl amines. all the new analogues 7a-s was characterized by their nmr and mass spectral ...201627184765
the effect of growth rate on pyrazinamide activity in mycobacterium tuberculosis - insights for early bactericidal activity?pyrazinamide (pza) plays an essential part in the shortened six-month tuberculosis (tb) treatment course due to its activity against slow-growing and non-replicating organisms. we tested whether pza preferentially targets slow growing cells of mycobacterium tuberculosis that could be representative of bacteria that remain after the initial kill with isoniazid (inh), by observing the response of either slow growing or fast growing bacilli to differing concentrations of pza.201627184366
[molecular characteristics of the multidrug-resistant mycobacterium tuberculosis strains in the northwest russia].the goal of this work was to study the genotypic characteristics of the multidrug-resistant (mdr, i.e., resistant to at least rifampicine and isoniazid) mycobacterium tuberculosis strains isolated in 2011-2012 from tuberculosis (tb) patients in the northwest russia. spoligotyping of 195 m. tuberculosis isolates identified 14 different spoligotypes and assigned isolates to the genetic families beijing (n = 162, 83%), lam (n = 15), h3/ural (n = 14), as well as t, haarlem and x. spoligotypes sit1 ( ...201627183719
heme oxygenase-1 regulates inflammation and mycobacterial survival in human macrophages during mycobacterium tuberculosis infection.mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. we previously showed that m. tuberculosis infection in mice induces expression of the co-producing enzyme heme oxygenase (ho1) and that co is sensed by m. tuberculosis to initiate a dormancy program. further, mice deficient in ho1 succumb to m. tuberculosis infection more readily than do wild-type mice. although mouse macrophages control intracellular m. tuberculosis infection through ...201627183573
maintenance of mycobacterium tuberculosis-specific t cell responses in end stage renal disease (esrd) and implications for diagnostic efficacy.end-stage renal disease (esrd) patients exhibit elevated risk of tuberculosis (tb) reactivation, but current diagnostics, including the interferon gamma release assay (igra), exhibit poor sensitivity in esrd. we tested 80 esrd patients and found an 18.75% prevalence of igra positivity. a subset of patients was assessed for mtb-specific expression of 44 cytokines/chemokines, and cd4+ t cell phenotype and function. similar to non-esrd igra+ individuals, mtb-specific ifnγ, il-1ra, ip-10, mcp-3 and ...201627181992
targeting multiple response regulators of mycobacterium tuberculosis augments the host immune response to infection.the genome of m. tuberculosis (mtb) encodes eleven paired two component systems (tcss) consisting of a sensor kinase (sk) and a response regulator (rr). the sks sense environmental signals triggering rr-dependent gene expression pathways that enable the bacterium to adapt in the host milieu. we demonstrate that a conserved motif present in the c-terminal domain regulates the dna binding functions of the ompr family of mtb rrs. molecular docking studies against this motif helped to identify two m ...201627181265
reynosin and santamarine: two sesquiterpene lactones from ambrosia confertiflora with bactericidal activity against clinical strains of mycobacterium tuberculosis.tuberculosis is primarily caused by mycobacterium tuberculosis (mtb). previous studies have shown that the dichloromethanic extract of ambrosia confertiflora dc (asteraceae) inhibited mtb.201627180996
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