Publications

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metal homeostasis in bacteria: the role of arsr-smtb family of transcriptional repressors in combating varying metal concentrations in the environment.bacterial infections cause severe medical problems worldwide, resulting in considerable death and loss of capital. with the ever-increasing rise of antibiotic-resistant bacteria and the lack of development of new antibiotics, research on metal-based antimicrobial therapy has now gained pace. metal ions are essential for survival, but can be highly toxic to organisms if their concentrations are not strictly controlled. through evolution, bacteria have acquired complex metal-management systems tha ...201728512703
identification of beta-lactamases and beta-lactam-related proteins in human pathogenic bacteria using a computational search approach.a systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. in this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. the amino acid sequences for 19 different types of beta-lactamases (act, carb, cifa, cmy, ctx, fox, ges, gob, imp, ind, kpc, len, okp, oxa, oxy, shv, tem, ndm, and vim) were obtained from the arg-annot database and were used to constru ...201728508147
salicylaldehyde and dihydroisobenzofuran derivatives from the marine fungus zopfiella marina.two salicylaldehyde derivatives (1 and 2), a hydroxymethylphenol (3), five dihydroisobenzofuran (4-8) derivatives, and a 5-chloro-3-deoxyisoochracinic acid (9), together with a known 3-deoxyisoochracinic acid (10) were isolated from the marine fungus zopfiella marina bcc 18240 (or nbrc 30420). the structures of these compounds were elucidated by extensive spectroscopic analysis. compound 1 showed weak antituberculous activity against mycobacterium tuberculosis h37ra, and antibacterial activity a ...201728669223
simultaneous detection of 13 key bacterial respiratory pathogens by combination of multiplex pcr and capillary electrophoresis.lower respiratory tract infections continue to pose a significant threat to human health. it is important to accurately and rapidly detect respiratory bacteria. to compensate for the limits of current respiratory bacteria detection methods, we developed a combination of multiplex polymerase chain reaction (pcr) and capillary electrophoresis (mpce) assay to detect thirteen bacterial pathogens responsible for lower respiratory tract infections, including streptococcus pneumoniae, haemophilus influ ...201728807095
trypanosoma infection favors brucella elimination via il-12/ifnγ-dependent pathways.this study develops an original co-infection model in mice using brucella melitensis, the most frequent cause of human brucellosis, and trypanosoma brucei, the agent of african trypanosomiasis. although the immunosuppressive effects of t. brucei in natural hosts and mice models are well established, we observed that the injection of t. brucei in mice chronically infected with b. melitensis induces a drastic reduction in the number of b. melitensis in the spleen, the main reservoir of the infecti ...201728824630
getting "inside" type i ifns: type i ifns in intracellular bacterial infections.type i interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. discovered in the context of viral infections, type i ifns are now known to have myriad effects in infectious and autoimmune disease settings. type i ifn signaling during bacterial infections is dependent on many factors including whether the infecting bacterium is intracellular or extracellular, as different signaling pathways are activated. as such, the repercussions ...201728529959
in vitro synergistic effects of a short cationic peptide and clinically used antibiotics against drug-resistant isolates of brucella melitensis.in the last few decades, increasing microbial resistance to common antibiotics has attracted researchers' attention to the development of new classes of antibiotics such as antimicrobial peptides. accordingly, the aim of the current study was to evaluate antimicrobial effects of the cm11 peptide alone and combined with common antibiotics against drug-resistant isolates of brucella melitensis.201728699872
discovery and biosynthesis of gladiolin: a burkholderia gladioli antibiotic with promising activity against mycobacterium tuberculosis.an antimicrobial activity screen of burkholderia gladioli bcc0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against mycobacterium tuberculosis h37rv. gladiolin is structurally related to etnangien, a highly unstable antibiotic from sorangium cellulosum that is also active against mycobacteria. like etnangien, gladiolin was found to inhibit rna polymerase, a validated drug target in m. tuberculosis. how ...201728528545
hydroxylamine-induced oxidation of ferrous carbonylated truncated hemoglobins from mycobacterium tuberculosis and campylobacter jejuni is limited by carbon monoxide dissociation.hydroxylamine (ha) is an oxidant of ferrous globins and its action has been reported to be inhibited by co, even though this mechanism has not been clarified. here, kinetics of the ha-mediated oxidation of ferrous carbonylated mycobacterium tuberculosis truncated hemoglobin n and o (mt-trhbn(ii)-co and mt-trhbo(ii)-co, respectively) and campylobacter jejuni truncated hemoglobin p (cj-trhbp(ii)-co), at ph 7.2 and 20.0 °c, are reported. mixing mt-trhbn(ii)-co, mt-trhbo(ii)-co, and cj-trhbp(ii)-co ...201728646425
rv3634c from mycobacterium tuberculosis h37rv encodes an enzyme with udp-gal/glc and udp-galnac 4-epimerase activities.a bioinformatics study revealed that mycobacterium tuberculosis h37rv (mtb) contains sequence homologs of campylobacter jejuni protein glycosylation enzymes. the orf rv3634c from mtb was identified as a sequence homolog of c. jejuni udp-gal/galnac 4-epimerase. this study reports the cloning of rv3634c and its expression as an n-terminal his-tagged protein. the recombinant protein was shown to have udp-gal/glc 4-epimerase activity by god-pod assay and by reverse phase hplc. this enzyme was shown ...201728403215
protein kinase c-delta (pkcδ), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice.we previously demonstrated that protein kinase c-δ (pkcδ) is critical for immunity against listeria monocytogenes, leishmania major, and candida albicans infection in mice. however, the functional relevance of pkcδ during mycobacterium tuberculosis (mtb) infection is unknown. pkcδ was significantly upregulated in whole blood of patients with active tuberculosis (tb) disease. lung proteomics further revealed that pkcδ was highly abundant in the necrotic and cavitory regions of tb granulomas in mu ...201728832027
whole blood profiling of bacillus calmette-guérin-induced trained innate immunity in infants identifies epidermal growth factor, il-6, platelet-derived growth factor-ab/bb, and natural killer cell activation.vaccination of infants with bacillus calmette-guérin (bcg) activates both the innate and adaptive arms of the immune response. the antimycobacterial effects of these responses most likely account for the ability of bcg to protect against childhood forms of tuberculosis (tb). there is also evidence for a heterologous protective effect of bcg vaccination against tb-unrelated mortality in low birth weight infants. a possible mechanism of action of this effect, the induction of trained innate immuni ...201728634479
robust immunoreactivity of teenager sera against peptide 19 from porphyromonas gingivalis hsp60.epitope spreading is a phenomenon in which distinct subdominant epitopes become major targets of the immune response. heat shock protein (hsp) 60 from porphyromonas gingivalis (pghsp60) and peptide 19 from pghsp60 (pep19) are immunodominant epitopes in autoimmune disease patients, including those with periodontitis. it remains unclear whether pep19 is a dominant epitope in subjects without periodontitis or autoimmune disease. the purpose of this study was to determine the epitope spreading patte ...201728680713
sphingolipids are dual specific drug targets for the management of pulmonary infections: perspective.sphingolipids are the major constituent of the mucus secreted by the cells of epithelial linings of lungs where they maintain the barrier functions and prevent microbial invasion. sphingolipids are interconvertible, and their primary and secondary metabolites have both structural and functional roles. out of several sphingolipid metabolites, sphingosine-1 phosphate (s1p) and ceramide are central molecules and decisive for sphingolipid signaling. these are produced by enzymatic activity of sphing ...201728400772
tpl2 promotes innate cell recruitment and effector t cell differentiation to limit citrobacter rodentium burden and dissemination.tumor progression locus 2 (tpl2) is a serine-threonine kinase that regulates th1 differentiation, secretion of the inflammatory cytokine ifnγ, and host defense against the intracellular pathogens toxoplasma gondii, listeria monocytogenes, and mycobacterium tuberculosis however, there is relatively little known about the contribution of tpl2 to th17 differentiation and immune cell function during infection with an extracellular pathogen. the goal of this study was to determine whether tpl2 influe ...201728760932
carboxyl analogue of mutacin 1140, a scaffold for lead antibacterial discovery.mutacin 1140 belongs to the epidermin group of lantibiotics. epidermin class lantibiotics are ribosomally synthesized and posttranslationally modified antibiotics with potent activity against gram-positive bacteria. in particular, this class is effective at targeting drug-resistant streptococcus pneumoniae, methicillin-resistant staphylococcus aureus (mrsa), mycobacterium tuberculosis, and clostridium difficile a c-terminal s-[(z)-2-aminovinyl]-d-cysteine (avicys) residue is derived from a decar ...201728500042
conformational control of udp-galactopyranose mutase inhibition.udp-galactopyranose mutase (glf or ugm) catalyzes the formation of uridine 5'-diphosphate-α-d-galactofuranose (udp-galf) from udp-galactopyranose (udp-galp). the enzyme is required for the production of galf-containing glycans. ugm is absent in mammals, but members of the corynebacterineae suborder require ugm for cell envelope biosynthesis. the need for ugm in some pathogens has prompted the search for inhibitors that could serve as antibiotic leads. optimizing inhibitor potency, however, has b ...201728608671
inhibitors of mycobacterium marinum virulence identified in a dictyostelium discoideum host model.tuberculosis remains one of the major threats to public health worldwide. given the prevalence of multi drug resistance (mdr) in mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. in this study, we used a dictyostelium discoideum host model to assess virulence ...201728727774
breaking fat! how mycobacteria and other intracellular pathogens manipulate host lipid droplets.tuberculosis (tb) is a lung infection caused by mycobacterium tuberculosis (mtb). with one third of the world population latently infected, it represents the most prevalent bacterial infectious diseases worldwide. typically, persistence is linked to so-called "dormant" slow-growing bacteria, which have a low metabolic rate and a reduced response to antibiotic treatments. however, dormant bacteria regain growth and virulence when the immune system is weakened, leading again to the active form of ...201728587792
immunodominance of adenovirus-derived cd8(+) t cell epitopes interferes with the induction of transgene-specific immunity in adenovirus-based immunization.adenovirus (ad)-based immunization is a popular approach in vaccine development, and ad-based vectors are renowned for their potential to induce strong cd8(+) t cell responses to the encoded transgene. surprisingly, we found before in the mouse friend retrovirus (fv) model that ad-based immunization did not induce cd8(+) t cell responses to the fv leader-gag-derived immunodominant epitope gagl85-93 we show now that induction of gagl85-93-specific cd8(+) t cells was highly effective when leader-g ...201728768877
identification of multiple druggable secondary sites by fragment screening against dc-sign.dc-sign is a cell-surface receptor for several pathogenic threats, such as hiv, ebola virus, or mycobacterium tuberculosis. multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. still, drug-like dc-sign ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. herein, we report on a parallel fragment screening against dc-sign applying spr and a reporter displace ...201728523851
ruptured pulmonary hydatid cyst: a case report.ruptured pulmonary hydatid cyst (phc) is an important clinical problem in endemic areas to echinococcal infection. herein we present a rare case of ruptured phc in an adolescent boy that was misdiagnosed as pulmonary tuberculosis in local health center. when sputum specimen was stained by acid-fast staining for detection of mycobacterium tuberculosis, hooklets of echinococcus granulosus were observed. a simple chest x-ray showed a multilobulated mass in the lower part of the left lung. computed ...201728848299
2,6-difluorobenzamide inhibitors of bacterial cell division protein ftsz: design, synthesis, and structure-activity relationships.a wide variety of drug-resistant microorganisms are continuously emerging, restricting the therapeutic options for common bacterial infections. antimicrobial agents that were originally potent are now no longer helpful, due to their weak or null activity toward these antibiotic-resistant bacteria. in addition, none of the recently approved antibiotics affect innovative targets, resulting in a need for novel drugs with innovative antibacterial mechanisms of action. the essential cell division pro ...201728586174
meso-dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.thirty-three meso-dihydroguaiaretic acid (meso-dga) derivatives bearing esters, ethers, and amino-ethers were synthesized. all derivatives were tested against twelve drug-resistant clinical isolates of gram-positive and gram-negative bacteria, including sensitive (h37rv) and multidrug-resistant mycobacterium tuberculosis strains. among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-res ...201728844400
phosphorylation of mycobacterial phosphodiesterase by eukaryotic-type ser/thr kinase controls its two distinct and mutually exclusive functionalities.phosphorylation mediated negative feed-back regulation of camp levels by phosphodiesterase is well established in eukaryotic cells. however, such mechanism remains unexplored in prokaryotes. we report here the involvement of eukaryotic-type ser/thr kinases, particularly pkna in trans-phosphorylating phosphodiesterase (mpde) from mycobacterium tuberculosis, which resulted in decreased enzyme turnover rate compared with its unphosphorylated counterpart. to elucidate the role of mpde phosphorylatio ...201728855253
structome analysis of escherichia coli cells by serial ultrathin sectioning reveals the precise cell profiles and the ribosome density.structome analysis, the quantitative three-dimensional structural analysis of whole cells at the electron microscopic level, of exophiala dermatitidis (black yeast), saccharomyces cerevisiae, mycobacterium tuberculosis (mtb) and myojin spiral bacteria (msb) have already been reported. here, the results of the structome analysis of escherichia coli cells based on transmission electron microscope observation of serial ultrathin sections was reported, and compared with the data obtained from phase ...201728854579
distinct mechanism evolved for mycobacterial rna polymerase and topoisomerase i protein-protein interaction.we report here a distinct mechanism of interaction between topoisomerase i and rna polymerase in mycobacterium tuberculosis and mycobacterium smegmatis that has evolved independently from the previously characterized interaction between bacterial topoisomerase i and rna polymerase. bacterial dna topoisomerase i is responsible for preventing the hyper-negative supercoiling of genomic dna. the association of topoisomerase i with rna polymerase during transcription elongation could efficiently reli ...201728843989
mechanism of transformation in mycobacteria using a novel shockwave assisted technique driven by in-situ generated oxyhydrogen.we present a novel method for shockwave-assisted bacterial transformation using a miniature oxyhydrogen detonation-driven shock tube. we have obtained transformation efficiencies of about 1.28 × 10(6), 1.7 × 10(6), 5 × 10(6), 1 × 10(5), 1 × 10(5) and 2 × 10(5) transformants/µg of dna for escherichia coli, salmonella typhimurum, pseudomonas aeruginosa, mycobacterium smegmatis, mycobacterium tuberculosis (mtb) and helicobacter pylori respectively using this method which are significantly higher th ...201728819202
exploring the potential of t7 bacteriophage protein gp2 as a novel inhibitor of mycobacterial rna polymerase.over the past six decades, there has been a decline in novel therapies to treat tuberculosis, while the causative agent of this disease has become increasingly resistant to current treatment regimens. bacteriophages (phages) are able to kill bacterial cells and understanding this process could lead to novel insights for the treatment of mycobacterial infections. phages inhibit bacterial gene transcription through phage-encoded proteins which bind to rna polymerase (rnap), thereby preventing bact ...201728802409
immuno-diagnosis of mycobacterium tuberculosis in sputum, and reduction of timelines for its positive cultures to within 3 h by pathogen-specific thymidylate kinase expression assays.laboratory diagnosis of tuberculosis (tb) is traditionally based on microscopy and or culture. microscopy is however, only sensitive to a specified degree of bacillary load not present in hiv co-infected persons. traditional cultures of mycobacterium tuberculosis (m. tb), on the other hand, take weeks to read-thereby delaying the critical decision whether or not, to treat. although nucleic acids amplification tests (naats) applied directly on sputum or cultures can increase the sensitivity for t ...201728789704
characterization of a minimal type of promoter containing the -10 element and a guanine at the -14 or -13 position in mycobacteria.three key promoter elements, -10, -35, and t-15g-14n, are recognized by the σ subunit of rna polymerase. among them, promoters with the -10 element and either of -35 or t-15g-14n consensuses are known to efficiently initiate transcription, but recent systematic analyses have identified a large group of promoters in mycobacterium tuberculosis that contain only a -10 consensus. how these promoters initiate transcription remains poorly understood. here, we show that promoters containing the -10 ele ...201728784819
common bacterial isolates, clinical outcome and tb meningitis in children admitted at morogoro regional referral hospital, tanzania.bacterial meningitis is still one of the major causes of deaths, disabilities, and mental retardation in children in morogoro region. to study the current meningitis burden, we evaluated the common bacterial isolates and clinical outcome of the disease in the region.201728776526
update on nitazoxanide: a multifunctional chemotherapeutic agent.the thiazolide nitazoxanide (ntz) is a broad-spectrum anti-infective drug that adversely affects viability, growth, and proliferation of a range of extracellular and intracellular protozoan, helminths, anaerobic and microaerophilic bacteria, and viruses.201728748751
immunological properties and protective efficacy of a single mycobacterial antigen displayed on polyhydroxybutyrate beads.in 2015, there were an estimated 10.4 million new tuberculosis (tb) cases and 1.4 million deaths worldwide. bacille calmette-guérin (bcg), an attenuated strain of mycobacterium bovis, is the vaccine available against tb, but it is insufficient for global tb control. this study evaluated the immunogenicity of the mycobacterium tuberculosis antigen rv1626 in mice while assessing the effect of co-delivering either cpe30 (immunostimulatory peptide), cs.t3378-395 (promiscuous t helper epitope) or fla ...201728714174
mutagenesis of threonine to serine in the active site of mycobacterium tuberculosis fructose-1,6-bisphosphatase (class ii) retains partial enzyme activity.the glpx gene encodes for the class ii fructose-1,6-bisphosphatase enzyme in mycobacterium tuberculosis (mt), an essential enzyme for pathogenesis. we have performed site directed mutagenesis to introduce two mutations at residue thr84, t84a and t84s, to explore the binding affinity of the substrate and the catalytic mechanism. the t84a mutant fully abolishes enzyme activity while retaining substrate binding affinity. in contrast, the t84s mutant retains some activity having a 10 times reduction ...201728702369
mycobacterium tuberculosis phoy proteins promote persister formation by mediating pst/senx3-regx3 phosphate sensing.the mycobacterium tuberculosis phosphate-specific transport (pst) system controls gene expression in response to phosphate availability by inhibiting the activation of the senx3-regx3 two-component system under phosphate-rich conditions, but the mechanism of communication between these systems is unknown. in escherichia coli, inhibition of the two-component system phor-phob under phosphate-rich conditions requires both the pst system and phou, a putative adaptor protein. e. coli phou is also inv ...201728698272
defining the functionally important domain and amino acid residues in mycobacterium tuberculosis integration host factor for genome stability, dna binding and integrative recombination.the integration host factor of mycobacterium tuberculosis (mihf) consists of a single polypeptide chain, the product of the ihf gene. we previously revealed that mihf is a novel member of a new class of nucleoid-associated proteins that have important roles in dna damage response, nucleoid compaction and integrative recombination. the mihf contains a region of 86 amino acids at its n-terminus, absent in both α- and β-subunits of escherichia coli ihf. however, the functional significance of an ex ...201728696279
plant e3 ligases ubiquitinate escherichia coli σ(32)in vitro.ubiquitin-like proteins (ubls) are extremely well-conserved among eukaryotes and prokaryotes allowing interactions between proteins from different organisms. for example, the prokaryotic ubiquitin-like proteins (pups) and the proteasome accessory factor a (pafa) of mycobacterium tuberculosis are sufficient to pupylate at least 51 escherichia coli proteins. this work shows that the plant e3 ligases bntr1 and at1g02860 can ubiquitinate e. coli σ(32), but not hsp70 dnak in vitro. molecular biology ...201728676399
glycosylation of recombinant antigenic proteins from mycobacterium tuberculosis: in silico prediction of protein epitopes and ex vivo biological evaluation of new semi-synthetic glycoconjugates.tuberculosis is still one of the most deadly infectious diseases worldwide, and the use of conjugated antigens, obtained by combining antigenic oligosaccharides, such as the lipoarabinomannane (lam), with antigenic proteins from mycobacterium tuberculosis (mtb), has been proposed as a new strategy for developing efficient vaccines. in this work, we investigated the effect of the chemical glycosylation on two recombinant mtb proteins produced in e. coli with an additional seven-amino acid tag (re ...201728661444
immunogenicity and protective efficacy of a fusion protein tuberculosis vaccine combining five esx family proteins.one strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on t cell antigens. in this study, we have evaluated the vaccine potential of a fusion protein combining esxb, esxd, esxg, esxu, and esxm of mycobacterium tuberculosis (m. tb). this recombinant protein, named bm, was expressed in and purified from escherichia coli. immunization of c57bl/6 mice with purified bm protein formulated in freund's incomplete adjuvant induced the production of th1 ...201728620588
crystal structure of rv1220c, a sam-dependent o-methyltransferase from mycobacterium tuberculosis.rv1220c from mycobacterium tuberculosis is annotated as an o-methyltransferase (mtbomt). currently, no structural information is available for this protein. here, the crystal structure of mtbomt refined to 2.0 å resolution is described. the structure reveals the presence of a methyltransferase fold and shows clear electron density for one molecule of s-adenosylmethionine (sam), which was apparently bound by the protein during its production in escherichia coli. although the overall structure of ...201728580918
rv3852 (h-ns) of mycobacterium tuberculosis is not involved in nucleoid compaction and virulence regulation.a handful of nucleoid-associated proteins (naps) regulate the vast majority of genes in a bacterial cell. h-ns, the histone-like nucleoid-structuring protein, is one of these naps and protects escherichia coli from foreign gene expression. though lacking any sequence similarity with e. coli h-ns, rv3852 was annotated as the h-ns ortholog in mycobacterium tuberculosis, as it resembles human histone h1. the role of rv3852 was thoroughly investigated by immunoblotting, subcellular localization, con ...201728559300
the protective effect of a novel antioxidant gene from mycobacterium avium against nitrosative and oxidative stress in e. coli.the production of reactive oxygen intermediates (roi) and reactive nitrogen intermediates (rni) is an important host defense mechanism in response to infection by mycobacterium tuberculosis. a variety of genes have been implicated in resistance to roi and rni, including noxr1. however, studies in mycobacterium avium, an important pathogen among nontuberculous mycobacteria, are limited. we aim to investigate the role of a novel gene cloned from m. avium with high similarity to noxr1, noa, in resi ...201728547728
recombinant bcg expressing ltak63 adjuvant induces superior protection against mycobacterium tuberculosis.in order to develop an improved bcg vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of escherichia coli heat labile enterotoxin (lt), ltak63. we have constructed rbcg strains expressing ltak63 at different expression levels. mice immunized with bcg expressing low levels of ltak63 (rbcg-ltak63lo) showed higher th1 cytokines and il-17 in the lungs, and when challenged intratracheally with mycobacterium tuberculosis displayed a 2.0-3.0 log r ...201728522873
evaluation of the mycobactericidal effect of thio-functionalized carbohydrate derivatives.sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. the replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. here, we evaluated the antibacterial activity of thio-functional ...201728509874
biochemical and functional characterization of mra_1571 of mycobacterium tuberculosis h37ra and effect of its down-regulation on survival in macrophages.amino acid biosynthesis has emerged as a source of new drug targets as many bacterial strains auxotrophic for amino acids fail to proliferate under in vivo conditions. branch chain amino acids (bcaas) are important for mycobacterium tuberculosis (mtb) survival and strains deficient in their biosynthesis were attenuated for growth in mice. threonine dehydratase (ilva) is a pyridoxal-5-phosphate (plp) dependent enzyme that catalyzes the first step in isoleucine biosynthesis. the mra_1571 of mycoba ...201728465237
preclinical development of bcg.hiva(2auxo.int), harboring an integrative expression vector, for a hiv-tb pediatric vaccine. enhancement of stability and specific hiv-1 t-cell immunity.one of the critical issues that should be addressed in the development of a bcg-based hiv vaccine is genetic plasmid stability. therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of bcg complemented with a plasmid carrying a wild-type complementing gene. in this study, we have constructed an integrative e. coli-mycobacterial shuttle plasmid, p2auxo.hiva(int), expressing the hiv-1 clade a immunogen hiva. this shuttle vector uses an antibiotic ...201728426273
selection of single-chain variable fragments specific for mycobacterium tuberculosis esat-6 antigen using ribosome display.tuberculosis (tb) is still one of the problematic infectious diseases in developing countries, especially in iran. in the present study, we applied ribosome display technique to select single chain variable fragments (scfvs) specific for the 6-kda early secretory antigenic target (esat-6) antigen of mycobacterium tuberculosis from a mouse scfv library.201728392906
a cassette containing thiostrepton, gentamicin resistance genes, and dif sequences is effective in construction of recombinant mycobacteria.the genetic manipulation of mycobacterium tuberculosis genome is limited by the availability of selection markers. spontaneous resistance mutation rate of m. tuberculosis to the widely used kanamycin is relatively high which often leads to some false positive transformants. due to the few available markers, we have created a cassette containing thiostrepton resistance gene (tsr) for selection in m. tuberculosis and m. bovis bcg, and gentamicin resistance gene (aacc1) for escherichia coli and m. ...201728392781
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
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