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fitting birth-death processes to panel data with applications to bacterial dna fingerprinting.continuous-time linear birth-death-immigration (bdi) processes are frequently used in ecology and epidemiology to model stochastic dynamics of the population of interest. in clinical settings, multiple birth-death processes can describe disease trajectories of individual patients, allowing for estimation of the effects of individual covariates on the birth and death rates of the process. such estimation is usually accomplished by analyzing patient data collected at unevenly spaced time points, r ...201726702330
interferon-γ release assays for the diagnosis of mycobacterium tuberculosis infection in children: a systematic review and meta-analysis.data regarding the use of interferon-gamma release assays (igras) for tuberculosis diagnosis are accumulating. we systematically searched pubmed, embase and cochrane and performed pooled estimates of sensitivity and specificity of quantiferon-tb gold in tube (qft-g-it) and t-spot.tb compared to tuberculin skin test (tst). for studies assessing sensitivity, children had to have active tuberculosis. specificity data were derived from children classified as non-infected. eleven studies were include ...201723058005
effectiveness of the bdprobetec et system for detection of mycobacterium tuberculosis complex in sputum and bronchoalveolar lavage specimens.the diagnostic efficacy of the bdprobetec et mycobacterium tuberculosis (mtb) complex direct detection assay (dtb) performed on bronchoalveolar lavage (bal) specimens and sputum smears was compared with acid-fast bacilli (afb) smear microscopy.201722729191
interferon-γ release assays for the diagnosis of mycobacterium tuberculosis infection in children: a literature review.the role of interferon-gamma release assays (igras) for immunologic diagnosis of tuberculosis in children is under debate. we carried out a narrative review on the studies on igras in paediatric populations. a literature search was conducted using multiple keywords and standardized terminology in medline, embase and cochrane databases, up to january 27th, 2011. study quality was assessed using the moose checklist and results of relevant studies were summarized. sixty-seven paediatric studies (st ...201722697065
previous use of quinolones: a surrogate marker for first line anti-tuberculosis drugs resistance in hiv-infected patients?drug resistant mycobacterium tuberculosis causes much higher rates of treatment toxicity, failure or relapse, and mortality. we determined the drug resistant profile of mycobacterium tuberculosis strains isolated from a population of hiv-infected patients in southern brazil and studied the potential factors associated with resistance.201722552455
characterization of gyra and gyrb mutations and fluoroquinolone resistance in mycobacterium tuberculosis clinical isolates from hubei province, china.the study aimed to investigate gyra and gyrb mutations in mycobacterium tuberculosis (mtb) clinical strains from 93 patients with pulmonary tuberculosis in hubei province, china, and analyze the association between mutation patterns of the genes and ofloxacin resistance level.201722552454
passenger contact investigation associated with a transport driver with pulmonary tuberculosis.in october 2008, pulmonary tuberculosis (tb) was diagnosed in a driver who had transported 762 passengers in the district of columbia metropolitan area during his infectious period. a passenger contact investigation was conducted by the six public health jurisdictions because of concern that some passengers might be infected with hiv or have other medical conditions that put them at increased risk for developing tb disease if infected.201722379220
rational design of diagnostic and vaccination strategies for tuberculosis.the development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus calmette-guérin (bcg) as vaccine in humans and animals. bcg_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. we carried out bioinformatics a ...201722358359
detection of genomic mutations in katg, inha and rpob genes of mycobacterium tuberculosis isolates using polymerase chain reaction and multiplex allele-specific polymerase chain reaction.isoniazid (inh) and rifampin (rif) are the most effective first line antibiotics against mycobacterium tuberculosis. mutations in several genes determine resistance of m. tuberculosis to inh, with the most common gene target of katg, and resistance to rif is due to mutation in rpob gene. the aim of present study was to assess the mutations in the regions related to rif and inh resistance.201722358357
nitazoxanide is active against mycobacterium leprae.nitazoxanide (ntz) is an anti-parasitic drug that also has activity against bacteria, including mycobacterium tuberculosis. our data using both radiorespirometry and live-dead staining in vitro demonstrate that ntz similarly has bactericidal against m. leprae. further, gavage of m. leprae-infected mice with ntz at 25mg/kg provided anti-mycobacterial activity equivalent to rifampicin (rif) at 10 mg/kg. this suggests that ntz could be considered for leprosy treatment.201728850614
microbial offense vs host defense: who controls the tb granuloma?the granuloma is the hallmark of tuberculosis and simultaneously signifies acquisition of an infection and induction of a host immune response. but who benefits more from the development of the granuloma, the host or the pathogen? is microbe or man dictating disease course and progression? mycobacterial diseases affect humans and animals alike, and the concepts presented in this review reflect host-pathogen interactions that influence not only mycobacterial granulomas in humans and animals but a ...201728749750
active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to mycobacterium marinum.the mechanisms governing neutrophil response to mycobacterium tuberculosis remain poorly understood. in this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to mycobacterium marinum, a close genetic relative of m. tuberculosis used to model tuberculosis. differential expression analysis following nuclear rna-seq of neutrophil active transcriptomes reveals a significan ...201728747644
phenotypic and genomic comparison of mycobacterium aurum and surrogate model species to mycobacterium tuberculosis: implications for drug discovery.tuberculosis (tb) is caused by mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. the considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating m. tuberculosis. these include the use of strains such as mycobacterium smegmatis and mycobacterium ma ...201728705154
a small-molecule allosteric inhibitor of mycobacterium tuberculosis tryptophan synthase.new antibiotics with novel targets are greatly needed. bacteria have numerous essential functions, but only a small fraction of such processes-primarily those involved in macromolecular synthesis-are inhibited by current drugs. targeting metabolic enzymes has been the focus of recent interest, but effective inhibitors have been difficult to identify. we describe a synthetic azetidine derivative, brd4592, that kills mycobacterium tuberculosis (mtb) through allosteric inhibition of tryptophan synt ...201728671682
β-ca-specific inhibitor dithiocarbamate fc14-584b: a novel antimycobacterial agent with potential to treat drug-resistant tuberculosis.inhibition of novel biological pathways in mycobacterium tuberculosis (mtb) creates the potential for alternative approaches for treating drug-resistant tuberculosis. in vitro studies have shown that dithiocarbamate-derived β-carbonic anhydrase (β-ca) inhibitors fc14-594 a and fc14-584b effectively inhibit the activity of mtb β-ca enzymes. we screened the dithiocarbamates for toxicity, and studied the in vivo inhibitory effect of the least toxic inhibitor on m. marinum in a zebrafish model. in o ...201728629306
ohmyungsamycins promote antimicrobial responses through autophagy activation via amp-activated protein kinase pathway.the induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against mycobacterium tuberculosis (mtb), a major pathogenic strain that causes human tuberculosis. in this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (oms) a and b in the antimicrobial responses against mtb infections by activating autophagy in murine bone marrow-derived macrophages (bmdms). oms robustly activated autophagy, which was essentiall ...201728611371
whib4 regulates the pe/ppe gene family and is essential for virulence of mycobacterium marinum.during the course of infection, pathogenic mycobacteria including mycobacterium tuberculosis (m. tb) encounter host environments of variable oxygen tension, ranging from the hypoxic center of granulomas to the most oxygenated region in the lung cavities. mycobacterial responses to changes of oxygen tension are critically related to infection outcomes, such as latency and reactivation. whib4 is an iron-sulfur containing transcription factor that is highly sensitive to oxygen exposure. in this stu ...201728592799
characterization of mycobacterium marinum infections in zebrafish wounds and sinus tracts.the impaired healing of mycobacterium tuberculosis-infected wounds is a clinical challenge, and the mechanisms involved are still not clear. the zebrafish model of mycobacterium marinum infection has provided surprising insights into the pathogenesis of tuberculosis in humans. similarly, the major principles and phases of cutaneous wound healing are conserved among adult mammals and adult zebrafish. here, we injected mycobacterium marinum into the dorsal muscles of adult zebrafish and observed t ...201728466489
immunogenicity and therapeutic effects of recombinant ag85ab fusion protein vaccines in mice infected with mycobacterium tuberculosis.the immune function of tuberculosis (tb) patients is disordered. by using immune regulators to assist chemotherapy for tb the curative effect might be improved. in this study, a vaccine containing mycobacterium tuberculosis (m. tuberculosis) recombinant ag85ab fusion protein (rag85ab) was constructed and evaluated. the mice were immunized intramuscularly three times at two-week intervals with ag85ab fusion protein combined with corynebacterium parvum adjuvant (rag85ab+cp). in comparison to contr ...201728625522
a versatile vector for mycobacterial protein production with a functional minimized acetamidase regulon.recombinant protein expression is a prerequisite for diverse investigations of proteins at the molecular level. for targets from mycobacterium tuberculosis it is favorable to use m. smegmatis as an expression host, a species from the same genus. in the respective shuttle vectors, target gene expression is controlled by the complex tetra-cistronic acetamidase regulon. as a result, the size of those vectors is large, rendering them of limited use, especially when the target proteins are expressed ...201728857325
inhibition of the devsr two-component system by overexpression of mycobacterium tuberculosis pknb in mycobacterium smegmatis.the devsr (dossr) two-component system, which is a major regulatory system involved in oxygen sensing in mycobacteria, plays an important role in hypoxic induction of many genes in mycobacteria. we demonstrated that overexpression of the kinase domain of mycobacterium tuberculosis (mtb) pknb inhibited transcriptional activity of the devr response regulator in mycobacterium smegmatis and that this inhibitory effect was exerted through phosphorylation of devr on thr180 within its dna-binding domai ...201728843272
two promoters in the esx-3 gene cluster of mycobacterium smegmatis respond inversely to different iron concentrations in vitro.the esx secretion system, also known as the type vii secretion system, is mostly found in mycobacteria and plays important roles in nutrient acquisition and host pathogenicity. one of the five esxs, esx-3, is associated with mycobactin-mediated iron acquisition. although the functions of some of the membrane-associated components of the esx systems have been described, the role of by mycosin-3 remains elusive. the esx-3 gene cluster encoding esx-3 in both mycobacterium tuberculosis and mycobacte ...201728841831
the α1β1 region is crucial for biofilm enhancement activity of mtc28 in mycobacterium smegmatis.we show here that mtc28, a secretory antigen of 28 kda from mycobacterium tuberculosis, is involved in biofilm formation. the exogenous addition of mtc28 to the culture medium as well its expression in mycobacterium smegmatis mc(2) 155 shows an enhancement in biofilm formation, which leads to drug resistance. structural analysis of mtc28 followed by mutational studies confirms the role of its α1β1 region in the biofilm enhancement activity. confocal and facs studies show that the α1β1 of mtc28 i ...201728833086
ppe27 in mycobacterium smegmatis enhances mycobacterial survival and manipulates cytokine secretion in mouse macrophages.mycobacterium tuberculosis pe/ppe family proteins play a vital role in antigenic diversity, host-pathogen interactions, and immune evasion. as secreted by esx-5 system, m. tuberculosis ppe27 is related to the growth and virulence of the bacilli. in this study, we expressed ppe27 in the nonpathogenic fast growing mycobacterium smegmatis. we found that the recombinant strain exhibits higher survival rate under several hostile conditions in vitro and longer persistence in mouse tissues. the surviva ...201728829246
the dynamic immunomodulatory effects of vitamin d3 during mycobacterium infection.mycobacterium tuberculosis ( mtb), is a highly infectious airborne bacterium. previous studies have found vitamin d3 to be a key factor in the defense against mtb infection, through its regulation of the production of immune-related cytokines, chemokines and effector molecules. mycobacterium smegmatis was used in our study as a surrogate of mtb. we hypothesized that the continuous presence of vitamin d3, as well as the level of severity of infection would differentially modulate host cell immune ...201728770668
identification of compounds that decrease numbers of mycobacteria in human macrophages in the presence of serum amyloid p.mϕs are a heterogeneous population of cells and include classically activated mϕs (m1) and alternatively activated mϕs (m2). mϕs can change from m1 to m2 and vice versa in response to environmental stimuli. serum amyloid p (sap) is a constitutive plasma protein that polarizes mϕs to an m2 phenotype, and part of this effect is mediated through fcγri receptors. in an effort to find ways to alter mϕs phenotypes, we screened for compounds that can block the sap-fcγri interaction. from a screen of 30 ...201728768708
complete auxotrophy for unsaturated fatty acids requires deletion of two sets of genes in mycobacterium smegmatis.the synthesis of unsaturated fatty acids in mycobacterium smegmatis is poorly characterized. bioinformatic analysis revealed four putative fatty acid desaturases in its genome, one of which, msmeg_1886, is highly homologous to desa3, the only palmitoyl/stearoyl desaturase present in the mycobacterium tuberculosis genome. a msmeg_1886 deletion mutant was partially auxotrophic for oleic acid and viable at 37°c and 25°c, although with a long lag phase in liquid medium. fatty acid analysis suggested ...201728762586
molecular and functional analysis of the mce4 operon in mycobacterium smegmatis.mycobacterium smegmatis contains 6 homologous mce (mammalian cell entry) operons which have been proposed to encode abc-like import systems. the mce operons encode up to 10 different proteins of unknown function that are not present in conventional abc transporters. we have analysed the consequences of individually deleting each of the genes of the mce4 operon of m. smegmatis, which mediates the transport of cholesterol. none of the mce4 mutants were able to grow in cholesterol suggesting that a ...201728752922
mycobacteria modify their cell size control under sub-optimal carbon sources.the decision to divide is the most important one that any cell must make. recent single cell studies suggest that most bacteria follow an "adder" model of cell size control, incorporating a fixed amount of cell wall material before dividing. mycobacteria, including the causative agent of tuberculosis mycobacterium tuberculosis, are known to divide asymmetrically resulting in heterogeneity in growth rate, doubling time, and other growth characteristics in daughter cells. the interplay between asy ...201728748182
mice bone marrow sca-1(+)/cd44(+)mesenchymal stem cells kill avirulent mycobacteria but not mycobacterium tuberculosis through modulation of cathelicidin expression via p38 mapk dependent pathway.mycobacterium tuberculosis (mtb) primarily infects lung macrophages. however, recent study has shown that mtb also infect and persist in dormant form inside the bone marrow mesenchymal stem cells (bm-mscs) even after successful antibiotic therapy. however, the mechanism(s) by which mtb survives in bm-mscs is still not known. like macrophages, bm-mscs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. here, we stud ...201728739828
role of long-chain acyl-coas in the regulation of mycolic acid biosynthesis in mycobacteria.one of the dominant features of the biology of mycobacterium tuberculosis, and other mycobacteria, is the mycobacterial cell envelope with its exceptional complex composition. mycolic acids are major and very specific components of the cell envelope and play a key role in its architecture and impermeability. biosynthesis of mycolic acid (ma) precursors requires two types of fatty acid synthases, fas i and fas ii, which should work in concert in order to keep lipid homeostasis tightly regulated. ...201728724694
modulation of trehalose dimycolate and immune system by rv0774c protein enhanced the intracellular survival of mycobacterium smegmatis in human macrophages cell line.mycobacterium tuberculosis rv0774c protein was reported previously to express under stress conditions. therefore, rv0774c gene was cloned and expressed in mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. the bacterial colonies expressing rv0774c (ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (ms_ve). enhanced survival of ms_rv0774c after treatment with streptomycin was observ ...201728713776
the putative polyketide cyclase msmeg_0129 from mycobacterium smegmatis: purification, crystallization and x-ray crystallographic analysis.mycobacterium tuberculosis rv0164 has previously been identified as a human t-cell antigen that induces significant production of ifn-γ in human peripheral blood mononuclear cells. m. smegmatis msmeg_0129 shares 59% sequence identity with rv0164. based on sequence alignment, both proteins are predicted to be members of the cyclase/dehydrase family, which is part of a large group of enzymes referred to as type ii polyketide synthases (pkss). in biosynthetic pathways mediated by type ii pkss, cycl ...201728695854
selection of a new mycobacterium tuberculosis h37rv aptamer and its application in the construction of a swcnt/aptamer/au-ide mspqc h37rv sensor.a rapid and accurate detection method for mycobacterium tuberculosis (m. tuberculosis) is essential for effectively treating tuberculosis. however, current detection methods cannot meet these clinical requirements because the methods are slow or of low specificity. consequently, a new highly specific ssdna aptamer against m. tuberculosis reference strain h37rv was selected by using the whole-cell systematic evolution of ligands by exponential enrichment technique. the selected aptamer was used t ...201728689112
the complete structure of the mycobacterium smegmatis 70s ribosome.the ribosome carries out the synthesis of proteins in every living cell. it consequently represents a frontline target in anti-microbial therapy. tuberculosis ranks among the leading causes of death worldwide, due in large part to the combination of difficult-to-treat latency and antibiotic resistance. here, we present the 3.3-å cryo-em structure of the 70s ribosome of mycobacterium smegmatis, a close relative to the human pathogen mycobacterium tuberculosis. the structure reveals two additional ...201728683309
mycobacterium tuberculosis hypoxic response protein 1 (hrp1) augments the pro-inflammatory response and enhances the survival of mycobacterium smegmatis in murine macrophages.the dosr/doss two-component regulatory system of mycobacterium tuberculosis regulates the expression of numerous genes under stress conditions and is important for the long-term survival of m. tuberculosis in the host. the rv2626c gene of m. tuberculosis is one of the most strongly induced transcripts of the dormancy regulon. this study focused on the immunological effects and possible function of rv2626c in maintaining mycobacterial survival under various stress conditions.201728671529
anti-tuberculosis bacteriophage d29 delivery with a vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler.to compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) d29 with three inhalation devices.201728646325
inhibition of biofilm formation in mycobacterium smegmatis by parinari curatellifolia leaf extracts.tuberculosis (tb) is a serious public health problem worldwide. mycobacterium tuberculosis (m. tuberculosis) grows as drug tolerant pellicles. agents that inhibit biofilm formation in m. tuberculosis have the potential to reduce the disease treatment period and improve the quality of tuberculosis chemotherapy. parinari curatellifolia (p. curatellifolia) leaf extracts are claimed to treat symptoms similar to tuberculosis in ethnomedicinal practices. mycobacterium smegmatis (m. smegmatis) is a sur ...201728558683
new isoflavonoids from the extract of rhynchosia precatoria (humb. & bonpl. ex willd.) dc. and their antimycobacterial activity.the evaluation of the antimycobacterial activity of extracts of medicinal plants used by mayos against tuberculosis and respiratory problems, allowed the identification of rhynchosia precatoria (humb. & bonpl. ex willd.) dc (fabaceae) as the best candidate to find new antimycobacterial compounds.201728506901
chemical activation of adenylyl cyclase rv1625c inhibits growth of mycobacterium tuberculosis on cholesterol and modulates intramacrophage signaling.mycobacterium tuberculosis (mtb) uses a complex 3', 5'-cyclic amp (camp) signaling network to sense and respond to changing environments encountered during infection, so perturbation of camp signaling might be leveraged to disrupt mtb pathogenesis. however, understanding of camp signaling pathways is hindered by the presence of at least 15 distinct adenylyl cyclases (acs). recently, the small molecule v-58 was shown to inhibit mtb replication within macrophages and stimulate camp production in m ...201728464471
unravelling the pleiotropic role of the mceg atpase in mycobacterium smegmatis.the mce systems are complex abc transporters that are encoded by different numbers of homologous operons in actinobacteria. while the four mce systems of mycobacterium tuberculosis are all energized by a single atpase, mceg, each system appears to import different fatty acids or sterols. to explore if this behaviour can be extended to saprophytic mycobacteria, whose more complex genomes encode more mce systems, we have identified and characterized the mceg orthologue of mycobacterium smegmatis. ...201728447386
anti-mycobacterium activity of microbial peptides in a silkworm infection model with mycobacterium smegmatis.an in vivo-mimic silkworm infection model with mycobacterium smegmatis was established. when silkworms were raised at 37 °c following an injection of m. smegmatis cells (1.25 × 10(7) cfu larva(-1) g(-1)) into the silkworm hemolymph, they died within 48 h. under these conditions, four microbial peptides with anti-m. smegmatis activity, lariatin a, calpinactam, lysocin e and propeptin, exerted therapeutic effects in a dose-dependent manner, and these are also clinically used agents that are active ...201728446822
mycobacterium tuberculosis pe_pgrs41 enhances the intracellular survival of m. smegmatis within macrophages via blocking innate immunity and inhibition of host defense.the success of mycobacterium tuberculosis (m. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. the genome of m. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic pe_ppe family. despite of intense research, the roles of pe_pgrs proteins in mycobacterial pathogenesis remain elusive. the function of m. tuberculosis pe_pgrs41, characterized by an extended and unique c-terminal domain, was s ...201728440335
identification of mycobacterial genes involved in antibiotic sensitivity: implications for the treatment of tuberculosis with β-lactam-containing regimens.in a mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaa, dpre2, rpst, and para displayed hypersusceptibility to antibiotics, including the β-lactams meropenem, ampicillin, amoxicillin, and cefotaxime. sub-mic levels of octoclothepin, a psychotic drug inhibiting para, phenocopied the para insertion and enhanced the bactericidal activity of meropenem against mycobacterium tuberculosis in combination with clavulanate. our study identifies novel factors associa ...201728438925
involvement of methylated hbha expressed from mycobacterium smegmatis in an ifn-γ release assay to aid discrimination between latent infection and active tuberculosis in bcg-vaccinated populations.ifn-γ release assays (igras) based on region of difference 1 (rd1) antigens have improved diagnosis of mycobacterium tuberculosis (m. tb) infection. however, igras with these antigens cannot discriminate between active tuberculosis (atb) and latent tuberculosis infection (ltbi). m. tb heparin-binding-hemagglutinin (hbha) induces relatively high ifn-γ responses in ltbi individuals and low responses in atb patients, but purification of the native methylated hbha from cultures of m. tb for immunolo ...201728429162
mutation at g103 of mtbftsz altered their sensitivity to coumarins.coumarins are natural polyphenol lactones comprising of fused rings of benzene and α-pyrone. the current study demonstrates the inhibitory effect of coumarins with various substitutions on mycobacterium smegmatis mc(2) 155. we also demonstrate the effect of pomegranate (punica granatum) extract containing ellagic acid, on m. smegmatis as well as their affect on mtbftsz (ftsz from mycobacterium tuberculosis). the ellagic acid extracts from pomegranate peels inhibit mycobacteria with a mic of 25 μ ...201728428773
biochemical and structural investigations on phosphoribosylpyrophosphate synthetase from mycobacterium smegmatis.mycobacterium smegmatis represents one model for studying the biology of its pathogenic relative mycobacterium tuberculosis. the structural characterization of a m. tuberculosis ortholog protein can serve as a valid tool for the development of molecules active against the m. tuberculosis target. in this context, we report the biochemical and structural characterization of m. smegmatis phosphoribosylpyrophosphate synthetase (prsa), the ortholog of m. tuberculosis prsa, the unique enzyme responsib ...201728419153
mycobacterium tuberculosis proteome response to antituberculosis compounds reveals metabolic "escape" pathways that prolong bacterial survival.tuberculosis (tb) continues to be one of the most common bacterial infectious diseases and is the leading cause of death in many parts of the world. a major limitation of tb therapy is slow killing of the infecting organism, increasing the risk for the development of a tolerance phenotype and drug resistance. studies indicate that mycobacterium tuberculosis takes several days to be killed upon treatment with lethal concentrations of antibiotics both in vitro and in vivo to investigate how metabo ...201728416555
synthetic (p)ppgpp analogue is an inhibitor of stringent response in mycobacteria.bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppgpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. in mycobacteria, the (p)ppgpp synthetase activity of bifunctional rel is critical for stress response and persistence inside a host. our aim was to design an inhib ...201728396544
characterization of a mycobacterial cellulase and its impact on biofilm- and drug-induced cellulose production.it was recently shown that mycobacterium tuberculosis produces cellulose which forms an integral part of its extracellular polymeric substances within a biofilm set-up. using mycobacterium smegmatis as a proxy model organism, we demonstrate that m. smegmatis biofilms treated with purified msmeg_6752 releases the main cellulose degradation-product (cellobiose), detected by using ionic chromatography, suggesting that msmeg_6752 encodes a cellulase. its overexpression in m. smegmatis prevents spont ...201728168306
solution nmr studies of mycobacterium tuberculosis proteins for antibiotic target discovery.tuberculosis is an infectious disease caused by mycobacteriumtuberculosis, which triggers severe pulmonary diseases. recently, multidrug/extensively drug-resistant tuberculosis strains have emerged and continue to threaten global health. because of the development of drug-resistant tuberculosis, there is an urgent need for novel antibiotics to treat these drug-resistant bacteria. in light of the clinical importance of m. tuberculosis, 2067 structures of m. tuberculsosis proteins have been determ ...201728858250
in silico drug design of thiolactomycin derivatives against mtb-kasa enzyme to inhibit multidrug resistance of mycobacterium tuberculosis.tuberculosis (tb) is a leading infectious disease which kills a huge number of people every year over a decade, caused by mycobacterium tuberculosis. the conventional drugs in the market are no longer effective due to the increasing mycobacterial resistance to antibiotics. hence, the need of finding efficient drugs to solve this multiple drug resistant factor is becoming an immediate issue. the first-line drugs in current practice for the treatment of tb emphasize on mycolic acid, which protects ...201728856604
activity of human beta defensin-1 and its motif against active and dormant mycobacterium tuberculosis.the ineffectiveness of anti-tuberculous therapy against dormant and drug-resistant mycobacteria demands scrutiny of alternative candidates like antimicrobial peptides having different mechanisms of action. the present study was designed to explore the activity of human beta defensin-1 (hbd-1) and its in silico identified short motif pep-b against active and dormant mycobacterium tuberculosis (m. tb) h37rv. activity of hbd-1 and pep-b was determined against actively growing m. tb in vitro, inside ...201728856417
diagnosis and treatment of pulmonary cavity after liver transplantation.although the outcomes have improved in the current era, pulmonary infection remains a significant post-transplant complication in liver transplant (lt) recipients. pulmonary infection with cavity formation often leads to higher mortality rates after lt. we wished to investigate the diagnosis and treatment of pulmonary cavity (pc) formation after lt.201728856141
sero-diagnosis of active mycobacterium tuberculosis disease among hiv co-infected persons using thymidylate kinase based antigen and antibody capture enzyme immuno-assays.clinical and laboratory diagnosis of active tuberculosis (atb) and latent mycobacterium tuberculosis (m. tuberculosis) infections (ltbi) among people living with hiv/aids (plwha) presents formidable challenges. in the past, who issued an advisory against the use of existing tb sero-diagnostics. emerging evidence, however, points to a precision of tb sero-diagnostics based on secretory rather than structural m. tuberculosis antigens. we hypothesized that secretory levels of m. tuberculosis thymid ...201728856068
memory of natural killer cells: a new chance against mycobacterium tuberculosis?natural killer (nk) cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. nk cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. their role in defense against mycobacterium tuberculosis (mtb) has been recently studied, and there is in ...201728855906
biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents.tuberculosis remains one of the world's deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. here, we show the isolation of six anti-mycobacterial ilamycin congeners (1-6) bearing rare l-3-nitro-tyrosine and l-2-amino-4-hexenoic acid structural units from the deep sea-derived streptomyces atratus scsio zh16. the biosynthesis of the rare l-3-nitrotyrosine and l-2-amino-4- ...201728855504
il-21 receptor signaling is essential for optimal cd4(+) t cell function and control of mycobacterium tuberculosis infection in mice.in this study, we determined the role of il-21r signaling in mycobacterium tuberculosis infection, using il-21r knockout (ko) mice. a total of 50% of m. tuberculosis h37rv-infected il-21r ko mice died in 6 mo compared with no deaths in infected wild type (wt) mice. m. tuberculosis-infected il-21r ko mice had enhanced bacterial burden and reduced infiltration of ag-specific t cells in lungs compared with m. tuberculosis-infected wt mice. ag-specific t cells from the lungs of m. tuberculosis-infec ...201728855309
the clinical recovery of tuberculosis patients undergoing specific treatment is associated with changes in the immune and neuroendocrine responses.tuberculosis (tb) caused by mycobacterium tuberculosis is a health problem worldwide. patients with pulmonary tb show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (dhea) levels. extending these findings, we now investigated the immune-endocrine profile of tb patients undergoing specific treatment. patients (n = 24) were bled at ...201728854691
decoding the similarities and differences among mycobacterial species.mycobacteriaceae comprises pathogenic species such as mycobacterium tuberculosis, m. leprae and m. abscessus, as well as non-pathogenic species, for example, m. smegmatis and m. thermoresistibile. genome comparison and annotation studies provide insights into genome evolutionary relatedness, identify unique and pathogenicity-related genes in each species, and explore new targets that could be used for developing new diagnostics and therapeutics. here, we present a comparative analysis of ten-myc ...201728854187
ppar-γ and akt regulate glut1 and glut3 surface localization during mycobacterium tuberculosis infection.the success of mycobacterium tuberculosis (mtb) as a pathogen stems from its ability to manipulate the host macrophage towards increased lipid biogenesis and lipolysis inhibition. inhibition of lipolysis requires augmented uptake of glucose into the host cell causing an upregulation of the glucose transporters glut1 and glut3 on the cell surface. mechanism behind this upregulation of the glut proteins during mtb infection is hitherto unknown and demands intensive investigation in order to unders ...201728852964
mycobacterium tuberculosis major facilitator superfamily transporters.the cell membrane or biofilm serve as permeable barrier for xenobiotics to maintain the homeostasis of cells or bacterial community. transport systems are essential for the uptake of nutrients and substances necessary for biofilm formation, efflux of deleterious compounds, as well as communication between cells and environment. major facilitator superfamily (mfs) represents the largest secondary transporter family and is responsible for the transport of a broad spectrum of substrates with divers ...201728852815
mycobacterium tuberculosis multidrug-resistant strain m induces low il-8 and inhibits tnf-α secretion by bronchial epithelial cells altering neutrophil effector functions.m strain, the most prevalent multidrug-resistant strain of mycobacterium tuberculosis (mtb) in argentina, has mounted mechanisms to evade innate immune response. the role of human bronchial epithelium in mtb infection remains unknown as well as its crosstalk with neutrophils (pmn). in this work, we evaluate whether m and h37rv strains invade and replicate within bronchial epithelial cell line calu-6 and how conditioned media (cm) derived from infected cells alter pmn responses. we demonstrated t ...201728852268
label-free optical vibrational spectroscopy to detect the metabolic state of m. tuberculosis cells at the site of disease.tuberculosis relapse is a barrier to shorter treatment. it is thought that lipid rich cells, phenotypically resistant to antibiotics, may play a major role. most studies investigating relapse use sputum samples although tissue bacteria may play an important role. we developed a non-destructive, label-free technique combining wavelength modulated raman (wmr) spectroscopy and fluorescence detection (nile red staining) to interrogate mycobacterium tuberculosis cell state. this approach could differ ...201728852109
a comprehensive study of interaction between peptidoglycan fragments and extracelluar domain of mycobacterium tuberculosis ser/thr kinase pknb.the mycobacterium tuberculosis ser/thr kinase pknb is implicated in the regulation of bacterial cell growth and cell division. the intracellular kinase function of pknb is thought to be triggered by peptidoglycan (pgn) fragments that are recognized by the extracytoplasmic domain of pknb. the pgn in the cell wall of m. tuberculosis has several unusual modifications including the presence of n-glycolyl groups (in addition to the n-acetyl groups) in the muramic acid residues, and amidation of d-glu ...201728851116
an application of competitive reporter monitored amplification (cma) for rapid detection of single nucleotide polymorphisms (snps).single nucleotide polymorphisms (snps) are essential parameters in molecular diagnostics and can be used for the early detection and clinical prognosis in various diseases. available methods for snp detection are still labor-intensive and require a complex laboratory infrastructure, which are not suitable for the usage in resource-limited settings. thus, there is an urgent need for a simple, reliable and rapid approach. in this paper we modified the previously developed competitive reporter moni ...201728850612
non-invasive lung disease diagnostics from exhaled microdroplets of lung fluid: perspectives and technical challenges.the combination of ultra-sensitive assay techniques and recent improvements in the instrumentation used to collect microdroplets of lung fluid (mlfs) from exhaled breath has enabled the development of noninvasive lung disease diagnostics that are based on mlf analysis. in one example of this approach, electrospun nylon filters were used to collect mlfs from patients with pulmonary tuberculosis. the filters were washed to obtain liquid probes that were then tested for human immunoglobulin a (h-ig ...201728850044
use of digital droplet pcr to detect mycobacterium tuberculosis dna in whole blood-derived dna samples from patients with pulmonary and extrapulmonary tuberculosis.tuberculosis (tb) is a chronic infectious disease that has been threatening public health for many centuries. the clinical diagnostic procedure for tb is time-consuming and laborious. in the last 20 years, real-time fluorescence-based quantitative pcr (real-time pcr) has become a better alternative for tb diagnosis in clinics due to its sensitivity and specificity. recently, digital droplet pcr (ddpcr) has been developed, and it might be an ideal alternative to conventional real-time pcr for mic ...201728848722
abdominal tuberculosis and spontaneous miscarriage.we present a case report of a 23-year-old pakistani woman who had a second trimester spontaneous miscarriage while visiting her family in the kingdom of saudi arabia. a dilatation and curettage (d&c) was done after the miscarriage. she developed sepsis and acute respiratory distress syndrome, requiring intensive care unit admission a few days after the d&c. an exploratory laparotomy was done and she was found to have a pelvic abscess. despite adequate broad spectrum antimicrobial cover, she cont ...201728847990
synthesis and in vitro investigation of halogenated 1,3-bis(4-nitrophenyl)triazenide salts as antitubercular compounds.the diverse pharmacological properties of the diaryltriazenes have sparked the interest to investigate their potential to be repurposed as antitubercular drug candidates. in an attempt to improve the antitubercular activity of a previously constructed diaryltriazene library, eight new halogenated nitroaromatic triazenides were synthesized and underwent biological evaluation. the potency of the series was confirmed against the mycobacterium tuberculosis lab strain h37ra and for the most potent de ...201728845550
integration of metabolomics and transcriptomics reveals a complex diet of mycobacterium tuberculosis during early macrophage infection.nutrient acquisition from the host environment is crucial for the survival of intracellular pathogens, but conceptual and technical challenges limit our knowledge of pathogen diets. to overcome some of these technical roadblocks, we exploited an experimentally accessible model for early infection of human macrophages by mycobacterium tuberculosis, the etiological agent of tuberculosis, to study host-pathogen interactions with a multi-omics approach. we collected metabolomics and complete transcr ...201728845460
phenolic glycolipid facilitates mycobacterial escape from microbicidal tissue-resident macrophages.mycobacterium tuberculosis (mtb) enters the host in aerosol droplets deposited in lung alveoli, where the bacteria first encounter lung-resident alveolar macrophages. we studied the earliest mycobacterium-macrophage interactions in the optically transparent zebrafish. first-responding resident macrophages phagocytosed and eradicated infecting mycobacteria, suggesting that to establish a successful infection, mycobacteria must escape out of the initially infected resident macrophage into growth-p ...201728844797
anthranilate phosphoribosyltransferase: binding determinants for 5'-phospho-alpha-d-ribosyl-1'-pyrophosphate (prpp) and the implications for inhibitor design.phosphoribosyltransferases (prts) bind 5'-phospho-α-d-ribosyl-1'-pyrophosphate (prpp) and transfer its phosphoribosyl group (prib) to specific nucleophiles. anthranilate prt (anprt) is a promiscuous prt that can phosphoribosylate both anthranilate and alternative substrates, and is the only example of a type iii prt. comparison of the prpp binding mode in type i, ii and iii prts indicates that anprt does not bind prpp, or nearby metals, in the same conformation as other prts. a structure with a ...201728844746
antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of psidium guineense sw. and spathulenol.leaves from psidium guineense sw. are used in popular medicine for the treatment of inflammatory disease. however, there is no scientific evidence demonstrating this activity.201728844678
relation of mycobacterium tuberculosis mutations at katg315 and inha-15 with drug resistance profile, genetic background, and clustering in argentina.we analyzed 362 isoniazid-resistant clinical isolates of mycobacterium tuberculosis obtained countrywide for the presence of mutation at katg315 and inha-15 in relation to genotype, pattern of phenotypic resistance to other drugs, and ability to spread. we found the following mutation frequencies: katg315mut/inha-15wt 53.0%, katg315wt/inha-15mut 27.4%, katg315wt/inha-15wt 19.3%, and katg315mut/inha-15mut only 0.3%. mutation at katg315 associated with the lam superfamily; mutation at inha-15 asso ...201728844342
clofazimine protects against mycobacterium tuberculosis dissemination in the cns following an aerosol challenge in a murine model.tuberculosis (tb) has been the scourge of the human race for many decades, claiming countless number of lives along the way. this is further complicated by the ability of mycobacterium tuberculosis (m.tb) to infect extra-pulmonary sites, more specifically the brain. these forms of tb are difficult to treat due to the problems associated with drug delivery across the blood brain barrier (bbb). linezolid (lzd and clofazimine (cfz) are two of the more promising anti-tb antibiotics in recent times.201728843822
activity of 2-(quinolin-4-yloxy)acetamides in mycobacterium tuberculosis clinical isolates and identification of their molecular target by whole genome sequencing.the 2-(quinolin-4-yloxy)acetamides (qoas) have been reported as promising molecules for tuberculosis treatment. recent studies demonstrated its potent antimycobacterial activity, as well as its biological stability and synergism with rifampicin. the identification of the molecular target is an essential step towards the development of a novel drug candidate. here we report the target identification of the qoas. we found that these compounds are active against isoniazid, rifampicin, ethambutol, s ...201728843821
specific immune responses in mice following subchronic exposure to acetamiprid.acetamiprid (ace) is an insecticide of the neonicotinoid family, the most widely used in the world. herein, we assessed the effect of ace on either the humoral or cellular immune responses of rodents. we also evaluated the role of curcumin in the restoration of altered immune responses after ace treatment.201728843496
inhibiting mycobacterial tryptophan synthase by targeting the inter-subunit interface.drug discovery efforts against the pathogen mycobacterium tuberculosis (mtb) have been advanced through phenotypic screens of extensive compound libraries. such a screen revealed sulfolane 1 and indoline-5-sulfonamides 2 and 3 as potent inhibitors of mycobacterial growth. optimization in the sulfolane series led to compound 4, which has proven activity in an in vivo murine model of mtb infection. here we identify the target and mode of inhibition of these compounds based on whole genome sequenci ...201728842600
structural basis of the pe-ppe protein interaction in mycobacterium tuberculosis.mycobacterium tuberculosis (mtb), the causative agent of tuberculosis, has developed multiple strategies to adapt to the human host. the five type vii secretion systems, esx-1-5, direct the export of many virulence-promoting protein effectors across the complex mycobacterial cell wall. one class of esx substrates is the pe/ppe family of proteins, which is unique to mycobacteria and essential for infection, antigenic variation and host-pathogen interactions. the genome of mtb encodes 168 pe/ppe p ...201728842489
rapid and visual detection of mycobacterium tuberculosis complex using recombinase polymerase amplification combined with lateral flow strips.to definitively diagnose active pulmonary tuberculosis (tb), mycobacterium tuberculosis complex (mtbc) bacilli must be identified within clinical specimens from patients. in this study, we introduced a rapid and visual detection method of mtbc using recombinase polymerase amplification (rpa) combined with lateral flow (lf) strips. the lf-rpa assay, read results with naked eyes, could detect as few as 5 genome copies of m. tuberculosis h37rv (atcc 27294) per reaction and had no cross-reactions wi ...201728842221
esrra (estrogen related receptor, alpha) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense.the orphan nuclear receptor essra (estrogen related receptor, alpha) is a key regulator of energy homeostasis and mitochondrial function. macroautophagy/autophagy, an intracellular degradation process, is a critical innate effector against intracellular microbes. here, we demonstrate that esrra is required for the activation of autophagy to promote innate antimicrobial defense against mycobacterial infection. amp-activated protein kinase pathway and sirt1 (sirtuin 1) activation led to induction ...201728841353
an expanding role for environmental microbes in shaping the immune response to infection with mycobacterium tuberculosis. 201728841029
interferon gamma release assay in response to pe35/ppe68 proteins: a promising diagnostic method for diagnosis of latent tuberculosis.tuberculosis control relies on the identification and preventive treatment of people who are latently infected with mycobacterium tuberculosis (mtb). pe/ppe proteins have been reported to elicit cd4 and/or cd8 responses either in the form of whole recombinant proteins or as individual peptides. very few of the pe and ppe proteins have been previously tested for responses in patients with tb and healthy donors. this is the first study to evaluate the interferon gamma release assay (igra) after st ...201728840843
bis-spirochromanones as potent inhibitors of mycobacterium tuberculosis: synthesis and biological evaluation.on the basis of reported antimycobacterial property of chroman-4-one pharmacophore, a series of chemically modified bis-spirochromanones were synthesized starting from 2-hydroxyacetophenone and 1,4-dioxaspiro[4.5] decan-8-one using a kabbe condensation approach. the synthesized bis-spirochromanones were established based on their spectral data and x-ray crystal structure of 6e. all synthesized compounds were evaluated against mycobacterium tuberculosis h37rv (atcc 27294) strain, finding that som ...201728840414
smear grading and the mantoux skin test can be used to predict sputum smear conversion in patients suffering from tuberculosis.purpose: smear scores and induration sizes resulting from the ppd (tuberculin purified protein derivative) test can serve as indicators of whether a patient suffering from tuberculosis shows smear conversion or not. methods: using microbiological methods smear and sputum tests, patients diagnosed as infected with mycobacterium tuberculosis between 2002 and 2015 were included in this study. all of the assumed factors that may have a role in smear conversion were studied, in addition to the prolon ...201728840092
molecular characterisation of isoniazid resistant clinical isolates of mycobacterium tuberculosis from khyber pakhtunkhwa, pakistan.to investigate the frequency of mutations in catalase-peroxidase and inhibin alpha genes in clinical isolates of isoniazid resistant mycobacterium tuberculosis strains.201728839308
correction for arora et al., "respiratory flexibility in response to inhibition of cytochrome c oxidase in mycobacterium tuberculosis". 201728839085
differences in pathogenicity of three animal isolates of mycobacterium species in a mouse model.animal mycobacterioses are among the most important zoonoses worldwide. these are generally caused by either mycobacterium tuberculosis (mtb), m. bovis (mbo) or m. avium (mav). to test the hypothesis that different species of pathogenic mycobacteria isolated from varied anatomic locations or animal species differ in virulence and pathogenicity, we performed experiments with three mycobacteria strains (ntse-3(mtb), ntse-4(mbo) and ntse-5 (mav)) obtained from animal species. spoligotyping analysis ...201728837698
immune characterization of the hbha-specific response in mycobacterium tuberculosis-infected patients with or without hiv infection.rd1-based interferon-γ release assays (igras) cannot distinguish latent from active tuberculosis (tb) disease. conversely, a positive response to heparin-binding haemagglutinin (hbha)-based igras, among tb-infected subjects, correlates with mycobacterium tuberculosis (mtb) containment and low risk of tb progression. the aim of this study was to characterize hbha-immune responses in hiv-infected and uninfected subjects with active tb or latent tb infection (ltbi).201728837654
assessment of the influence of direct tobacco smoke on infection and active tb management.smoking is a risk factor for tuberculosis (tb) infection and disease progression. tobacco smoking increases susceptibility to tb in a variety of ways, one of which is due to a reduction of the ifn-γ response. consequently, an impaired immune response could affect performance of ifn-γ release assays (igras).201728837570
preclinical assessment of a (68)ga-dota-functionalized depsipeptide as a radiodiagnostic infection imaging agent.the study assessed a radiolabeled depsipeptide conjugate ((68)ga-dota-tbia101) for its potential as an imaging agent targeting infection or infection-associated inflammation. (68)ga-labeled dota-tbia101 imaging was performed in (nzr1) healthy rabbits; (nzr2) rabbits bearing muscular sterile inflammation and staphylococcus aureus (sa) infection; and (nzr3) rabbits infected with mycobacterium tuberculosis (mtb) combined with a subcutaneous scruff infection of sa in the same animal. all animals wer ...201728837117
tuberculosis in healthcare workers, scotland.in an attempt to explore healthcare worker acquisition of tuberculosis infection, we conducted population-based surveillance of all cases recorded as healthcare workers reported to enhanced surveillance of mycobacterial infection from 2000 to 2015. over the study period, the mean incidence rate of tuberculosis among all healthcare workers was 15.4 per 100,000 healthcare workers. however, the incidence rate of tuberculosis amongst those healthcare workers born outside the uk was 164.8 per 100,000 ...201728836925
metabolic activity of mature biofilms of mycobacterium tuberculosis and other non-tuberculous mycobacteria.mycobacteria are classified into two groups, fast- and slow-growing. often, fast-growing mycobacteria are assumed to have a higher metabolic activity than their slower counterparts, but in mature biofilms this assumption might not be correct. indeed, when measuring the metabolic activity of mycobacterial biofilms with two independent non-invasive techniques (isothermal microcalorimetry and tunable diode laser absorption spectrometry), mature biofilms of slow- and fast-growing species appeared mo ...201728835629
evolutionary pathway analysis and unified classification of east asian lineage of mycobacterium tuberculosis.due to its rapid spread and association with the numerous outbreaks, the global spread of east asian lineage of mycobacterium tuberculosis strains presents a global concern. although there were many attempts to describe its population structure, no consensus has been reached yet. to define unbiased classification that will facilitate future studies of this lineage, we analyzed the performance and congruence of eight different genotyping schemes based on phylogenetic analysis of 1,398 strains fro ...201728835627
development of water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents.in this work, four series of tertiary amine-containing derivatives of 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. we found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. the n-benzylpiperazine derivatives, which had the highest lipophilicity among all of the series, showed the highest in vitro antimycobacterial activities against mycobacterium tuberculosis cnctc ...201728835350
irak-m alters the polarity of macrophages to facilitate the survival of mycobacterium tuberculosis.intracellular bacterium, mycobacterium tuberculosis (m. tb), infects specifically macrophages as host cells. irak-m, a member of irak family, is a negative regulator in tlr signaling and specifically expresses in monocytes and macrophages. the role of irak-m in intracellular growth of m. tb and macrophage polarization was explored, for deeply understanding the pathogenesis of m. tb, the significance of irak-m to innate immunity and pathogen-host interaction.201728835201
mechanism of the nitric oxide dioxygenase reaction of mycobacterium tuberculosis hemoglobin n.many globins convert •no to innocuous no3(-) through their nitric oxide dioxygenase (nod) activity. mycobacterium tuberculosis fights the oxidative and nitrosative stress imposed by its host (the toxic effects of o2•(-) and •no species and their oono(-) and •no2 derivatives) through the action of truncated hemoglobin n (trhbn), which catalyzes the nod reaction with one of the highest rates among globins. the general nod mechanism comprises the following steps: binding of o2 to the heme, diffusio ...201728835102
total synthesis and mass spectrometric analysis of a mycobacterium tuberculosis phosphatidylglycerol featuring a two-step synthesis of (r)-tuberculostearic acid.we report the total synthesis of (r)-tuberculostearic acid-containing mycobacterium tuberculosis phosphatidylglycerol (pg). the approach features a two-step synthesis of (r)-tuberculostearic acid, involving an (s)-citronellyl bromide linchpin, and the phosphoramidite-assisted assembly of the full pg structure. collision-induced dissociation mass spectrometry of two chemically-synthesized pg acyl regioisomers revealed diagnostic product ions formed by preferential loss of carboxylate at the secon ...201728831486
new amide and dioxopiperazine derivatives from leaves of breynia nivosa.the first chemical investigation of leaves of breynia nivosa from nigeria resulted in the isolation of two new amide derivatives breynivosamides a and b (1 and 2) and two new dioxopiperazine derivatives breynivosines a and b (4 and 5) together with seven known compounds (3, 6-11). the structures of the new compounds were elucidated by 1d, 2d nmr and hresims data as well as by comparison with the literature. all isolated compounds were tested for the cytotoxic and antimicrobial activities. only c ...201728830789
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