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crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from mycobacterium tuberculosis.mycobacterium tuberculosis (mtb) infects one-third of the world's population and in 2013 accounted for 1.5 million deaths. fluoroquinolone antibacterials, which target dna gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. to better explain known differences in fluoroquinolone action, the crystal structures of the wt mtb dna ...201626792525
a rheostat mechanism governs the bifurcation of carbon flux in mycobacteria.fatty acid metabolism is an important feature of the pathogenicity of mycobacterium tuberculosis during infection. consumption of fatty acids requires regulation of carbon flux bifurcation between the oxidative tca cycle and the glyoxylate shunt. in escherichia coli, flux bifurcation is regulated by phosphorylation-mediated inhibition of isocitrate dehydrogenase (icd), a paradigmatic example of post-translational mechanisms governing metabolic fluxes. here, we demonstrate that, in contrast to e. ...201627555519
the duf59 containing protein suft is involved in the maturation of iron-sulfur (fes) proteins during conditions of high fes cofactor demand in staphylococcus aureus.proteins containing duf59 domains have roles in iron-sulfur (fes) cluster assembly and are widespread throughout eukarya, bacteria, and archaea. however, the function(s) of this domain is unknown. staphylococcus aureus suft is composed solely of a duf59 domain. we noted that suft is often co-localized with sufbc, which encode for the suf fes cluster biosynthetic machinery. phylogenetic analyses indicated that suft was recruited to the suf operon, suggesting a role for suft in fes cluster assembl ...201627517714
mycobacterium tuberculosis devr/dosr dormancy regulator activation mechanism: dispensability of phosphorylation, cooperativity and essentiality of α10 helix.devr/dosr is a well-characterized regulator in mycobacterium tuberculosis which is implicated in various processes ranging from dormancy/persistence to drug tolerance. devr induces the expression of an ~48-gene dormancy regulon in response to gaseous stresses, including hypoxia. strains of the beijing lineage constitutively express this regulon, which may confer upon them a significant advantage, since they would be 'pre-adapted' to the environmental stresses that predominate during infection. a ...201627490491
cell-envelope remodeling as a determinant of phenotypic antibacterial tolerance in mycobacterium tuberculosis.the mechanisms that lead to phenotypic antibacterial tolerance in bacteria remain poorly understood. we investigate whether changes in nacl concentration toward physiologically higher values affect antibacterial efficacy against mycobacterium tuberculosis (mtb), the causal agent of human tuberculosis. indeed, multiclass phenotypic antibacterial tolerance is observed during mtb growth in physiologic saline. this includes changes in sensitivity to ethionamide, ethambutol, d-cycloserine, several am ...201627231718
mollicutes/hiv coinfection and the development of aids: still far from a definitive response.background. mycoplasmas are known to cause various infections in humans, mainly in the respiratory and urogenital tracts. the different species are usually host-specific and cause diseases in well-defined sites. new species have been isolated, including those from hiv-infected persons. summary. its in vitro properties, combined with clinical findings, have led to the hypothesis that these microorganisms may act as cofactors of hiv in aids development. even today this point of view is quite polem ...201627413383
interspecies communication between pathogens and immune cells via bacterial membrane vesicles.the production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. prokaryotes secrete 50-250 nm membrane vesicles (mvs) in a manner that is regulated by environmental stress and is thought to promote survival. since many types of host-derived stress are encountered during infection, this implies an important role for mv secretion in bacterial pathogenesis. accordingly, mvs produced by gram-positive and gram-negative pathogens con ...201627891500
chromosomal rearrangements and protein globularity changes in mycobacterium tuberculosis isolates from cerebrospinal fluid.meningitis is a major cause of mortality in tuberculosis (tb). it is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of mycobacterium tuberculosis (mtb) might have genetic traits associated with neurotropism.201627688977
heterozygous stat1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype.since their discovery in patients with autosomal dominant (ad) chronic mucocutaneous candidiasis (cmc) in 2011, heterozygous stat1 gain-of-function (gof) mutations have increasingly been identified worldwide. the clinical spectrum associated with them needed to be delineated. we enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. the median age of the 274 pati ...201627114460
reconstruction of diaminopimelic acid biosynthesis allows characterisation of mycobacterium tuberculosis n-succinyl-l,l-diaminopimelic acid desuccinylase.with the increased incidence of tuberculosis (tb) caused by mycobacterium tuberculosis there is an urgent need for new and better anti-tubercular drugs. n-succinyl-l,l-diaminopimelic acid desuccinylase (dape) is a key enzyme in the succinylase pathway for the biosynthesis of meso-diaminopimelic acid (meso-dap) and l-lysine. dape is a zinc containing metallohydrolase which hydrolyses n-succinyl l,l diaminopimelic acid (l,l-nsdap) to l,l-diaminopimelic acid (l,l-dap) and succinate. m. tuberculosis ...201626976706
respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in cape town, south africa.lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. children with symptoms suggestive of pulmonary tuberculosis (ptb) may have tuberculosis, other respiratory tract infections or co-infection with mycobacterium tuberculosis and other pathogens. we aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (np) samples from children with suspected ptb.201627776489
performance of an in-house real-time polymerase chain reaction for identification of mycobacterium tuberculosis isolates in laboratory routine diagnosis from a high burden setting.brazil is one of the high burden countries for tuberculosis, and a rapid diagnosis is essential for effective control of the disease. in the present study, an in-house real-time polymerase chain reaction (pcr) assay targeting the mpt64 gene for identification of mycobacterium tuberculosis complex isolates was evaluated under routine diagnosis conditions in a reference laboratory. from may 2011 to july 2012, 1,520 isolates of mycobacteria were prospectively submitted for phenotypic and/or pra-hsp ...201627598243
antitubercular drugs for an old target: gsk693 as a promising inha direct inhibitor.despite being one of the first antitubercular agents identified, isoniazid (inh) is still the most prescribed drug for prophylaxis and tuberculosis (tb) treatment and, together with rifampicin, the pillars of current chemotherapy. a high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme katg, so the discovery of direct inhibitors (di) of the enoyl-acp reductase (inha) has been pursued by many groups leading to the identification of different enzyme inhib ...201627428438
infectious discitis and spondylodiscitis in children.in children, infectious discitis (d) and infectious spondylodiscitis (sd) are rare diseases that can cause significant clinical problems, including spinal deformities and segmental instabilities. moreover, when the infection spreads into the spinal channel, d and sd can cause devastating neurologic complications. early diagnosis and treatment may reduce these risks. the main aim of this paper is to discuss recent concepts regarding the epidemiology, microbiology, clinical presentation, diagnosis ...201627070599
the role of neutrophils in the induction of specific th1 and th17 during vaccination against tuberculosis.mycobacterium tuberculosis causes tuberculosis (tb), a disease that killed more than 1.5 million people worldwide in 2014, and the bacillus calmette guérin (bcg) vaccine is the only currently available vaccine against tb. however, it does not protect adults. th1 and th17 cells are crucial for tb control, as well as the neutrophils that are directly involved in dc trafficking to the draining lymph nodes and the activation of t lymphocytes during infection. although several studies have shown the ...201627375607
disulfide-bond-forming pathways in gram-positive bacteria.disulfide bonds are important for the stability and function of many secreted proteins. in gram-negative bacteria, these linkages are catalyzed by thiol-disulfide oxidoreductases (dsb) in the periplasm. protein oxidation has been well studied in these organisms, but it has not fully been explored in gram-positive bacteria, which lack traditional periplasmic compartments. recent bioinformatics analyses have suggested that the high-gc-content bacteria (i.e., actinobacteria) rely on disulfide-bond- ...201626644434
vaccines directed against microorganisms or their products present during biofilm lifestyle: can we make a translation as a broad biological model to tuberculosis?tuberculosis (tb) remains as a global public health problem. in recent years, experimental evidence suggesting the relevance of in vitro pellicle (a type of biofilm formed at the air-liquid interface) production as a phenotype mimicking aspects found by mycobacterium tuberculosis-complex bacteria during in vivo infection has started to accumulate. there are still opportunities for better diagnostic tools, therapeutic molecules as well as new vaccine candidates to assist in tb control programs wo ...201626834732
the two domains of mycobacterium tuberculosis nusg protein are dynamically independent.transcription elongation factor nusg from escherichia coli couples transcription and translation. it is the only conserved transcription factor in all three kingdoms of life, playing a variety of roles in gene expression. e. coli nusg consists of two non-interacting domains. while the n-terminal domain interacts with rna polymerase, the c-terminal domain contacts nuse (s10), or the rho transcription termination factor. the two corresponding domains of thermotoga maritima nusg are mutually intera ...201625931133
triacylglycerol and wax ester-accumulating machinery in prokaryotes.gram negative bacteria as well as gram positive actinobacteria possess the ability to accumulate variable amounts of wax esters (we) and/or triacylglycerols (tag) under nitrogen limiting conditions. in recent years many advances have been made to obtain insight into neutral lipid biosynthesis and accumulation in prokaryotes. the clinical and industrial relevance of bacterial we/tag significantly promoted basic and applied research in this field. the recent integrated omic studies as well as the ...201626343555
mycobacterium tuberculosis pe25/ppe41 protein complex induces activation and maturation of dendritic cells and drives th2-biased immune responses.mycobacterium tuberculosis evades innate host immune responses by parasitizing macrophages and causes significant morbidity and mortality around the world. a mycobacterial antigen that can activate dendritic cells (dcs) and elicit effective host innate immune responses will be vital to the development of an effective tb vaccine. the m. tuberculosis genes pe25/ppe41 encode proteins which have been associated with evasion of the host immune response. we constructed a pe25/ppe41 complex gene via sp ...201626318856
a lacz reporter-based strategy for rapid expression analysis and target validation of mycobacterium tuberculosis latent infection genes.we report a novel lacz fusion vector and demonstrate its utility for expression analysis of genes associated with mycobacterium tuberculosis latent infection. the vector contains e. coli (orie) and mycobacterial (orim) origins of replication, a kanamycin resistance gene (km(r)) as selection marker, and a lacz reporter gene in fusion with mcs for cloning of upstream regulatory sequence of the desired genes. β-galactosidase activity of the vector was standardized for expression analysis under late ...201626597215
lipoprotein lpri of mycobacterium tuberculosis acts as a lysozyme inhibitor.mycobacterium tuberculosis executes numerous defense strategies for the successful establishment of infection under a diverse array of challenges inside the host. one such strategy that has been delineated in this study is the abrogation of lytic activity of lysozyme by a novel glycosylated and surface-localized lipoprotein, lpri, which is exclusively present in m. tuberculosis complex. the lpri gene co-transcribes with the glbn gene (encoding hemoglobin (hbn)) and both are synchronously up-regu ...201626589796
identification and functional annotation of mycobacterial septum formation genes using cell division mutants of escherichia coli.the major virulence trait of mycobacterium tuberculosis is its ability to enter a latent state in the face of robust host immunity. clues to the molecular basis of latency can emerge from understanding the mechanism of cell division, beginning with identification of proteins involved in this process. using complementation of escherichia coli mutants, we functionally annotated m. tuberculosis and mycobacterium smegmatis homologs of divisome proteins ftsw and amic. our results demonstrate that e. ...201626577656
insights from the structure of mycobacterium tuberculosis topoisomerase i with a novel protein fold.the dna topoisomerase i enzyme of mycobacterium tuberculosis (mttop1) is essential for the viability of the organism and survival in a murine model. this topoisomerase is being pursued as a novel target for the discovery of new therapeutic agents for the treatment of drug-resistant tuberculosis. in this study, we succeeded in obtaining a structure of mttop1 by first predicting that the c-terminal region of mttop1 contains four repeated domains that do not involve the zn-binding tetracysteine mot ...201626655023
mycobacterium tuberculosis uvrb is a robust dna-stimulated atpase that also possesses structure-specific atp-dependent dna helicase activity.much is known about the escherichia coli nucleotide excision repair (ner) pathway; however, very little is understood about the proteins involved and the molecular mechanism of ner in mycobacteria. in this study, we show that mycobacterium tuberculosis uvrb (mtuvrb), which exists in solution as a monomer, binds to dna in a structure-dependent manner. a systematic examination of mtuvrb substrate specificity reveals that it associates preferentially with single-stranded dna, duplexes with 3' or 5' ...201627618337
reconstruction and topological characterization of the sigma factor regulatory network of mycobacterium tuberculosis.accessory sigma factors, which reprogram rna polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. here we reconstruct the complete sigma factor regulatory network of the human pathogen mycobacterium tuberculosis by an integrated approach. the approach combines identification of direct regulatory interactions between m. tuberculosis sigma factors in an e. coli model system, validation of selected links in m. tuberculosis, and extensive litera ...201627029515
transition state structure and inhibition of rv0091, a 5'-deoxyadenosine/5'-methylthioadenosine nucleosidase from mycobacterium tuberculosis.5'-methylthioadenosine/s-adenosylhomocysteine nucleosidase (mtan) is a bacterial enzyme that catalyzes the hydrolysis of the n-ribosidic bond in 5'-methylthioadenosine (mta) and s-adenosylhomocysteine (sah). mtan activity has been linked to quorum sensing pathways, polyamine biosynthesis, and adenine salvage. previously, the coding sequence of rv0091 was annotated as a putative mtan in mycobacterium tuberculosis. rv0091 was expressed in escherichia coli, purified to homogeneity, and shown to be ...201627019223
recombinant preparation and functional studies of espi atp binding domain from mycobacterium tuberculosis.the esx-1 secretion system of mycobacterium tuberculosis is required for the virulence of tubercle bacillus. espi, the esx-1 secretion-associated protein in mycobacterium tuberculosis (mtespi), is involved in repressing the activity of esx-1-mediated secretion when the cellular atp level is low. the atp binding domain of mtespi plays a crucial role in this regulatory process. however, further structural and functional studies of mtespi are hindered due to the bottleneck of obtaining stable and p ...201627017992
mycobacterium tuberculosis peptidyl-prolyl isomerases also exhibit chaperone like activity in-vitro and in-vivo.peptidyl-prolyl cis-trans isomerases (ppiases), also known as cyclophilins, are ubiquitously expressed enzymes that assist in protein folding by isomerization of peptide bonds preceding prolyl residues. mycobacterium tuberculosis (m.tb) is known to possess two ppiases, ppia and ppib. however, our understanding about the biological significance of mycobacterial ppiases with respect to their pleiotropic roles in responding to stress conditions inside the macrophages is restricted. this study descr ...201626981873
interaction of mycobacterium tuberculosis virulence factor ripa with chaperone moxr1 is required for transport through the tat secretion system.mycobacterium tuberculosis is a leading cause of death worldwide. the m. tuberculosis tat (twin-arginine translocation) protein secretion system is present at the cytoplasmic membrane of mycobacteria and is known to transport folded proteins. the tat secretion system is reported to be essential for many important bacterial processes that include cell wall biosynthesis. the m. tuberculosis secretion and invasion protein ripa has endopeptidase activity and interacts with one of the resuscitation a ...201626933057
eukaryotic-type ser/thr protein kinase mediated phosphorylation of mycobacterial phosphodiesterase affects its localization to the cell wall.phosphodiesterase enzymes, involved in camp hydrolysis reaction, are present throughout phylogeny and their phosphorylation mediated regulation remains elusive in prokaryotes. in this context, we focused on this enzyme from mycobacterium tuberculosis. the gene encoded by rv0805 was pcr amplified and expressed as a histidine-tagged protein (mpde) utilizing escherichia coli based expression system. in kinase assays, upon incubation with mycobacterial clade i eukaryotic-type ser/thr kinases (pkna, ...201626904001
proteome-wide lysine glutarylation profiling of the mycobacterium tuberculosis h37rv.lysine glutarylation, a new protein posttranslational modification (ptm), was recently identified and characterized in both prokaryotic and eukaryotic cells. to explore the distribution of lysine glutarylation in mycobacterium tuberculsosis, by using a comprehensive method combining the immune affinity peptide enrichment by the glutaryl-lysine antibody with lc-ms, we finally identified 41 glutarylation sites in 24 glutarylated proteins from m. tuberculosis. these glutarylated proteins are involv ...201626903315
combined bioinformatic and rational design approach to develop antimicrobial peptides against mycobacterium tuberculosis.drug-resistant pathogens are a growing problem, and novel strategies are needed to combat this threat. among the most significant of these resistant pathogens is mycobacterium tuberculosis, which is an unusually difficult microbial target due to its complex membrane. here, we design peptides for specific activity against m. tuberculosis using a combination of "database filtering" bioinformatics, protein engineering, and de novo design. several variants of these peptides are structurally characte ...201626902758
a multistage mycobacterium tuberculosis subunit vaccine lt70 including latency antigen rv2626c induces long-term protection against tuberculosis.to develop an effective subunit vaccine which could target tubercle bacilli with different metabolic states and provide effective protective immunity, we fused antigens esat6, ag85b, peptide 190-198 of mpt64, and mtb8.4 mainly expressed by proliferating bacteria and latency-associated antigen rv2626c together to construct a multistage protein esat6-ag85b-mpt64(190-198)-mtb8.4-rv2626c (lt70 for short) with the molecular weight of 70 kda. the human t-cell responses to lt70 and other antigens were ...201626901244
gene regulatory network inference using fused lasso on multiple data sets.devising computational methods to accurately reconstruct gene regulatory networks given gene expression data is key to systems biology applications. here we propose a method for reconstructing gene regulatory networks by simultaneous consideration of data sets from different perturbation experiments and corresponding controls. the method imposes three biologically meaningful constraints: (1) expression levels of each gene should be explained by the expression levels of a small number of transcri ...201626864687
characterization of lipoyl synthase from mycobacterium tuberculosis.the prevalence of multiple and extensively drug-resistant strains of mycobacterium tuberculosis (mtb), the causative agent of tuberculosis, is on the rise, necessitating the identification of new targets to combat an organism that has infected one-third of the world's population, according to the world health organization. the biosynthesis of the lipoyl cofactor is one possible target, given its critical importance in cellular metabolism and the apparent lack of functional salvage pathways in mt ...201626841001
lysine acetylation of the mycobacterium tuberculosis hu protein modulates its dna binding and genome organization.nucleoid-associated protein hu, a conserved protein across eubacteria is necessary for maintaining the nucleoid organization and global regulation of gene expression. mycobacterium tuberculosis hu (mthu) is distinct from the other orthologues having 114 amino acid long carboxyl terminal extensions with a high degree of sequence similarity to eukaryotic histones. in this study, we demonstrate that the dna binding property of mthu is regulated by posttranslational modifications akin to eukaryotic ...201626817737
mycobacterium tuberculosis ruvx is a holliday junction resolvase formed by dimerisation of the monomeric yqgf nuclease domain.the mycobacterium tuberculosis genome possesses homologues of the ruvc and yqgf genes that encode putative holliday junction (hj) resolvases. however, their gene expression profiles and enzymatic properties have not been experimentally defined. here we report that expression of ruvc and yqgf is induced in response to dna damage. protein-dna interaction assays with purified m. tuberculosis ruvc (mtruvc) and yqgf (mtruvx) revealed that both associate preferentially with hj dna, albeit with differi ...201626817626
endoscope-assisted pectoralis major-rectus abdominis bipedicle muscle flap for the treatment of poststernotomy mediastinitis.various management strategies have been reported for sternal wound care; however, they exhibit limited effectiveness or are associated with severe complications. furthermore, it is difficult for the standard pectoralis major (pm) muscle advance flap to reach the lower third of the sternum. this article examines using the pm-rectus abdominis (ra) bipedicle muscle flap to treat lower-third deep sternal wound infection.201626808741
characterization of rv0888, a novel extracellular nuclease from mycobacterium tuberculosis.bacterial extracellular nucleases play important roles in virulence, biofilm formation, utilization of extracellular dna as a nutrient, and degradation of neutrophil dna extracellular traps. however, there is no current data available for extracellular nucleases derived from m. tuberculosis. herein, we have identified and characterized rv0888, an extracellular nuclease in m. tuberculosis. the protein was overexpressed in e. coli, and the purified rv0888 protein was found to require divalent cati ...201626742696
trna is a new target for cleavage by a mazf toxin.toxin-antitoxin (ta) systems play key roles in bacterial persistence, biofilm formation and stress responses. the mazf toxin from the escherichia coli mazef ta system is a sequence- and single-strand-specific endoribonuclease, and many studies have led to the proposal that mazf family members exclusively target mrna. however, recent data indicate some mazf toxins can cleave specific sites within rrna in concert with mrna. in this report, we identified the repertoire of rnas cleaved by mycobacter ...201626740583
mycobacterium tuberculosis espb protein suppresses interferon-γ-induced autophagy in murine macrophages.mycobacterium tuberculosis (mtb) persists within immature phagosomes by preventing their maturation into phagolysosomes. although the early secretory antigenic target 6 (esat-6) system 1 (esx-1) secretion-associated protein b (espb) of mtb is strongly linked to immunogenicity and virulence of this organism, its mechanism of action remains largely unclear. this study aimed to investigate espb effects on autophagy in murine ana-1 macrophage cells.201625641595
streptomycin affinity depends on 13 amino acids forming a loop in homology modelled ribosomal s12 protein (rpsl gene) of lysinibacillus sphaericus dsls5 associated with marine sponge (tedania anhelans).streptomycin, an antibiotic used against microbial infections, inhibits the protein synthesis by binding to ribosomal protein s12, encoded by rpsl12 gene, and associated mutations cause streptomycin resistance. a streptomycin resistant, lysinibacillus sphaericus dsls5 (mic >300 µg/ml for streptomycin), was isolated from a marine sponge (tedania anhelans). the characterisation of rpsl12 gene showed a region having similarity to long terminal repeat sequences of murine lukemia virus which added 13 ...201626198082
automated device for asynchronous extraction of rna, dna, or protein biomarkers from surrogate patient samples.many biomarker-based diagnostic methods are inhibited by nontarget molecules in patient samples, necessitating biomarker extraction before detection. we have developed a simple device that purifies rna, dna, or protein biomarkers from complex biological samples without robotics or fluid pumping. the device design is based on functionalized magnetic beads, which capture biomarkers and remove background biomolecules by magnetically transferring the beads through processing solutions arrayed within ...201626194105
autoregulation of topoisomerase i expression by supercoiling sensitive transcription.the opposing catalytic activities of topoisomerase i (topoi/relaxase) and dna gyrase (supercoiling enzyme) ensure homeostatic maintenance of bacterial chromosome supercoiling. earlier studies in escherichia coli suggested that the alteration in dna supercoiling affects the dna gyrase and topoi expression. although, the role of dna elements around the promoters were proposed in regulation of gyrase, the molecular mechanism of supercoiling mediated control of topoi expression is not yet understood ...201626496944
selection of nucleic acid aptamers specific for mycobacterium tuberculosis.tuberculosis (tb) remains to be a major global health problem, with about 9 million new cases and 1.4 million deaths in 2011. for the control of tuberculosis as well as other infectious diseases, who recommended "assured" (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to the end user) diagnostic tools that can easily be maintained and used in developing countries. aptamers are promising tools for developing point-of-care diagnostic assays for t ...201626541162
roles of triolein and lipolytic protein in the pathogenesis and survival of mycobacterium tuberculosis: a novel therapeutic approach.discovery of novel secreted enzymes and proteins in mycobacterium tuberculosis (m. tuberculosis) are imperative to understanding the pathogenic system for pathogenesis requires attention. till date, the groups of these secreted enzymes are not meaningfully characterized in terms of m. tuberculosis. in this way, cutinase, a small lipolytic protein, exists in both bacteria and fungi as well which have a potential catalytic activity. during our search, we have found a few genes of m. tuberculosis d ...201626679705
fluoroquinolone consumption and -resistance trends in mycobacterium tuberculosis and other respiratory pathogens: ecological antibiotic pressure and consequences in pakistan, 2009-2015.fluoroquinolones (fqs) are important anti-tuberculous drugs for the treatment of multidrug-resistant (mdr) tuberculosis. resistance to fqs leads to fewer options for treatment of tuberculosis (tb), and infection with such strains may also require longer treatment duration. trends of resistance in mycobacterium tuberculosis (mtb) are indicators of mtb-resistance evolution. drivers of such resistance need to be understood and studied to inform preventive strategies.201627931682
trend of bacterial meningitis in bahrain from 1990 to 2013 and effect of introduction of new vaccines.meningitis is among the 10 commonest infectious causes of death worldwide. this retrospective analysis of reported cases of meningitis in bahrain aimed to assess the trend in the incidence of bacterial meningitis from 1990 to 2013, before and after the introduction of new vaccines. of 1455 reported cases of meningitis during the study period 73.1% were viral and 26.9% were bacterial etiology (tuberculous meningitis 8.3%; streptococcus pneumoniae 4.9%, haemophilus influenzae 3.6% and neisseria me ...201627334074
a case of good's syndrome presenting with pulmonary tuberculosis.adult onset immunodeficiency associated with thymoma is a rare condition. the combination of hypogammaglobulinemia, reduced number of peripheral b and cd4+ t cells, along with thymoma constitutes good's syndrome (gs). this immunodeficiency condition is often complicated with opportunistic infection with organisms, like bacteria (haemophilus influenzae, streptococcus pneumonia etc), viruses (cytomegalovirus, herpes simplex etc), fungi and protozoa. we present an unusual case of good's syndrome wi ...201627164735
usage of murine t-cell hybridoma cells as responder cells reveals interference of helicobacter pylori with human dendritic cell-mediated antigen presentation.direct effects of helicobacter pylori (h. pylori) on human cd4(+) t-cells hamper disentangling a possible bacterial-mediated interference with major histocompatibility complex class ii (mhc-ii)-dependent antigen presentation to these cells. to overcome this limitation, we employed a previously described assay, which enables assessing human antigen-processing cell function by using murine t-cell hybridoma cells restricted by human leukocyte antigen (hla) alleles. hla-dr1(+) monocyte-derived dendr ...201627980859
freezing the dynamic gap for selectivity: motion-based design of inhibitors of the shikimate kinase enzyme.shikimate kinase (sk), the fifth enzyme of the aromatic amino acid biosynthesis, is a recognized target for antibiotic drug discovery. the potential of the distinct dynamic apolar gap, which isolates the natural substrate from the solvent environment for catalysis, and the motion of mycobacterium tuberculosis and helicobacter pylori sk enzymes, which was observed by molecular dynamics simulations, was explored for inhibition selectivity. the results of the biochemical and computational studies r ...201627699905
stool microbiome reveals diverse bacterial ureases as confounders of oral urea breath testing for helicobacter pylori and mycobacterium tuberculosis in bamako, mali.detection of bacterial urease activity has been utilized successfully to diagnose helicobacter pylori (h. pylori). while mycobacterium tuberculosis (m. tuberculosis) also possesses an active urease, it is unknown whether detection of mycobacterial urease activity by oral urease breath test (ubt) can be exploited as a rapid point of care biomarker for tuberculosis (tb) in humans. we enrolled 34 individuals newly diagnosed with pulmonary tb and 46 healthy subjects in bamako, mali and performed ora ...201627532494
targeting the motion of shikimate kinase: development of competitive inhibitors that stabilize an inactive open conformation of the enzyme.the large conformational changes observed by molecular dynamics simulation studies on the product release in the lid and shikimic acid binding (sb) domains of the shikimate kinase (sk) enzyme have been exploited in the development of reversible competitive inhibitors against sk from mycobacterium tuberculosis and helicobacter pylori. this enzyme is a recognized target for antibiotic drug discovery. the reported c5-substituted shikimic acid analogues interact with the dynamic apolar pocket that s ...201627191386
study of the phosphoryl-transfer mechanism of shikimate kinase by nmr spectroscopy.the phosphoryl-transfer mechanism of shikimate kinase from mycobacterium tuberculosis and helicobacter pylori, which is an attractive target for antibiotic drug discovery, has been studied by 1d (1)h and (31)p nmr spectroscopy. metaphosphoric acid proved to be a good mimetic of the metaphosphate intermediate and facilitated the ready and rapid evaluation by nmr spectroscopic analysis of a dissociative mechanism. the required closed form of the active site for catalysis was achieved by the use of ...201626797764
inhibition of shikimate kinase and type ii dehydroquinase for antibiotic discovery: structure-based design and simulation studies.the loss of effectiveness of current antibiotics caused by the development of drug resistance has become a severe threat to public health. current widely used antibiotics are surprisingly targeted at a few bacterial functions - cell wall, dna, rna, and protein biosynthesis - and resistance to them is widespread and well identified. there is therefore great interest in the discovery of novel drugs and therapies to tackle antimicrobial resistance, in particular drugs that target other essential pr ...201626303426
reconstruction of vertebral bone defects using an expandable replacement device and bioactive glass s53p4 in the treatment of vertebral osteomyelitis: three patients and three pathogens.bioactive glass s53p4 is an antibacterial bone substitute with bone-bonding and osteostimulative properties. the bone substitute has been successfully used clinically in spine; trauma; orthopedic; ear, nose, and throat; and cranio-maxillofacial surgeries. bioactive glass s53p4 significantly reduces the amount of bacteria in vitro and possesses the capacity to kill both planktonic bacteria and bacteria in biofilm. three patients with severe spondylodiscitis caused by mycobacterium tuberculosis, c ...201626929284
novel halogenated pyrazine-based chalcones as potential antimicrobial drugs.chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal and antimycobacterial activity. the highest potency was exhibited by derivatives with electron withdrawing groups (ewg) in positions 2 and 4 of the ring b. as halo ...201627801810
modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids.although n-3 long-chain polyunsaturated fatty acids (n-3 lc-pufas) are used widely in the treatment of chronic inflammatory diseases, their effect in infectious disease requires a particular attention.201627746159
the making and taking of lipids: the role of bacterial lipid synthesis and the harnessing of host lipids in bacterial pathogenesis.in order to survive environmental stressors, including those induced by growth in the human host, bacterial pathogens will adjust their membrane physiology accordingly. these physiological changes also include the use of host-derived lipids to alter their own membranes and feed central metabolic pathways. within the host, the pathogen is exposed to many stressful stimuli. a resulting adaptation is for pathogens to scavenge the host environment for readily available lipid sources. the pathogen ta ...201627720012
activator of g-protein signaling 3-induced lysosomal biogenesis limits macrophage intracellular bacterial infection.many intracellular pathogens cause disease by subverting macrophage innate immune defense mechanisms. intracellular pathogens actively avoid delivery to or directly target lysosomes, the major intracellular degradative organelle. in this article, we demonstrate that activator of g-protein signaling 3 (ags3), an lps-inducible protein in macrophages, affects both lysosomal biogenesis and activity. ags3 binds the gi family of g proteins via its g-protein regulatory (goloco) motif, stabilizing the g ...201626667172
community-acquired pneumonia: a global perspective.community-acquired pneumonia (cap) is a global disease responsible for a large proportion of deaths and having significant economic cost. as diagnostic tools have increased in sensitivity, our understanding of the etiology of cap has begun to change with a significant increase in confirmed viral infections and the recognition that multiple pathogens are frequently present. empiric therapy remains the standard of care and guidelines are mostly based on published data from the united states or eur ...201627960204
polyphosphate kinase mediates antibiotic tolerance in extraintestinal pathogenic escherichia coli pcn033.extraintestinal pathogenic escherichia coli (expec) causes a variety of acute infections in its hosts, and multidrug-resistant strains present significant challenges to public health and animal husbandry. therefore, it is necessary to explore new drug targets to control e. coli epidemics. previous studies have reported that ppk mutants of burkholderia pseudomallei and mycobacterium tuberculosis are more susceptible than the wild types (wts) to stress. therefore, we investigated the stress respon ...201627242742
tuberculosis and pulmonary candidiasis co-infection present in a previously healthy patient.the coexistance among fungal pathogens and tuberculosis pulmonary is a clinical condition that generally occurs in immunosuppressive patients, however, immunocompetent patients may have this condition less frequently.201627546933
maternal milk t cells drive development of transgenerational th1 immunity in offspring thymus.using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam- and pup-derived cells, we show that foster nursing by an immunized dam results in development of cd8(+) t cells in nonimmunized foster pups that are specific for ags against which the foster dam was immunized (mycobacterium tuberculosis or candida albicans). we have dubbed this process "maternal educational immunity" to distinguish it from passive cellular immunity. of t ...201627496970
bortezomib inhibits bacterial and fungal β-carbonic anhydrases.inhibition of the β-carbonic anhydrases (cas, ec 4.2.1.1) from pathogenic fungi (cryptococcus neoformans, candida albicans, candida glabrata, malassezia globosa) and bacteria (three isoforms from mycobacterium tuberculosis, rv3273, rv1284 and rv3588), as well from the insect drosophila melanogaster (dmeca) and the plant flaveria bidentis (fbica1) with the boronic acid peptidomimetic proteosome inhibitor bortezomib was investigated. bortezomib was a micromolar inhibitor of all these enzymes, with ...201627469982
homology model, molecular dynamics simulation and novel pyrazole analogs design of candida albicans cyp450 lanosterol 14 α-demethylase, a target enzyme for antifungal therapy.candida albicans infections and their resistance to clinically approved azole drugs are major concerns for human. the azole antifungal drugs inhibit the ergosterol synthesis by targeting lanosterol 14α-demethylase of cytochrome p450 family. the lack of high-resolution structural information of fungal pathogens has been a barrier for the design of modified azole drugs. thus, a preliminary theoretical molecular dynamic study is carried out to develop and validate a simple homologous model using cr ...201627142238
choline and geranate deep eutectic solvent as a broad-spectrum antiseptic agent for preventive and therapeutic applications.antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the food and drug administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. this vulnerable position calls for urgent identification of novel antiseptic agents. recently, the ability of a deep eutectic, choline and geranate (cage), to treat biofilms o ...201626959835
novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: synthesis, antibacterial, antitubercular and antimalarial activities.a series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. the newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against mycobacterium tuberculosis h37rv and antimalarial activity against plasmodium falciparum. most of them exhibited significant antibacterial activity as compared to the first line dru ...201626900659
infection is the major trigger of hemophagocytic syndrome in adult patients treated with biological therapies.hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, hlh) are characterized by a wide range of etiologies, symptoms, and outcomes, but have a common etiopathogenic pathway leading to organ damage: an excessive inflammatory response. biological therapies have been proposed as a therapeutic option for refractory hlh, but have also been related to the development of hlh in severe immunosuppressed patients.201626277577
recombinant bacillus subtilis spores for the delivery of mycobacterium tuberculosis ag85b-cfp10 secretory antigens.tuberculosis continues to be a great cause of morbidity and mortality in different parts of the world. unfortunately, the current bcg vaccine being administered is not fully protective against tuberculosis; therefore, there is a great need for alternate vaccines. with an aim to develop such vaccines, we have analyzed the utility of bacillus subtilis spores for the expression of two major immunodominant antigens of mycobacterium tuberculosis, ag85b and cfp10. we created three recombinant b. subti ...201627727129
computational operon prediction in whole-genomes and metagenomes.microbial diversity in unique environmental settings enables abrupt responses catalysed by altering the gene regulation and formation of gene clusters called operons. operons increases bacterial adaptability, which in turn increases their survival. this review article presents the emergence of computational operon prediction methods for whole microbial genomes and metagenomes, and discusses their strengths and limitations. most of the whole-genome operon prediction methods struggle to generalize ...201627659221
design, synthesis and biological evaluation of novel azaspiro analogs of linezolid as antibacterial and antitubercular agents.the design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of linezolid (1) have been described. linezolid comprises of a morpholine ring which is known for its metabolism-related liabilities. therefore, the key modification made in the linezolid structure was the replacement of morpholine moiety with its bioisostere, 2-oxa-6-azaspiro[3.3]heptane. furthermore, the replacement of n-acetyl terminal of 1 with various aromatic or aliphatic functionalities was carried ...201627423637
fine-tuning of substrate affinity leads to alternative roles of mycobacterium tuberculosis fe2+-atpases.little is known about iron efflux transporters within bacterial systems. recently, the participation of bacillus subtilis pfet, a p1b4-atpase, in cytoplasmic fe(2+) efflux has been proposed. we report here the distinct roles of mycobacterial p1b4-atpases in the homeostasis of co(2+) and fe(2+) mutation of mycobacterium smegmatis ctpj affects the homeostasis of both ions. alternatively, an m. tuberculosis ctpj mutant is more sensitive to co(2+) than fe(2+), whereas mutation of the homologous m. t ...201627022029
shape and size engineered cellulosic nanomaterials as broad spectrum anti-microbial compounds.oxidized celluloses have been used for decades as antimicrobial wound gauzes and surgical cotton. we now report the successful synthesis of a next generation narrow size range (25-35nm) spherical shaped nanoparticles of 2,3,6-tricarboxycellulose based on cellulose i structural features, for applications as new antimicrobial materials. this study adds to our previous study of 6-carboxycellulose. a wide range of bacteria such as escherichia coli, staphloccocus aureus, bacillus subtilis and mycobac ...201626968926
synthesis, in vitro antimycobacterial evaluation and docking studies of some new 5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3h)-one schiff bases.development of multidrug resistant (mdr) and extensively drug resistant (xdr) tuberculosis (tb) has been considered as major health burden, globally. in order to develop novel, potential molecules against drug resistant tb, twenty two (22) new 3-substituted-7-benzyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3h)-one (6a-k) and 3-substituted-7-benzyl-2-methyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3h)-one (7a-k) derivatives were designed and synthesized by us ...201626755393
ebselen and analogs as inhibitors of bacillus anthracis thioredoxin reductase and bactericidal antibacterials targeting bacillus species, staphylococcus aureus and mycobacterium tuberculosis.bacillus anthracis is the causative agent of anthrax, a disease associated with a very high mortality rate in its invasive forms.201626971857
dimerization of bacterial diaminopimelate decarboxylase is essential for catalysis.diaminopimelate decarboxylase (dapdc) catalyzes the final step in the diaminopimelate biosynthesis pathway of bacteria. the product of the reaction is the essential amino acid l-lysine, which is an important precursor for the synthesis of the peptidoglycan cell wall, housekeeping proteins, and virulence factors of bacteria. accordingly, the enzyme is a promising antibacterial target. previous structural studies demonstrate that dapdc exists as monomers, dimers, and tetramers in the crystal state ...201626921318
highly sensitive sequence specific qpcr detection of mycobacterium tuberculosis complex in respiratory specimens.nucleic acid amplification tests for mycobacterium tuberculosis (mtb) detection from sputum are highly sensitive and specific with smear microscopy positive specimens, but their sensitivity with smear-negative/culture-positive specimens is much lower; therefore, these tests cannot rule out a tuberculosis diagnosis. co-extraction of pcr inhibitors may be a cause of decreased test sensitivity. here the design and early validation of a mtb screening assay with sample preparation and qpcr methods de ...201627865380
antimicrobial compounds from endophytic streptomyces sp. bcc72023 isolated from rice (oryza sativa l.).an endophytic actinomycete strain bcc72023 was isolated from rice (oryza sativa l.) and identified as the genus streptomyces, based on phenotypic, chemotaxonomic and 16s rrna gene sequence analyses. the strain showed 99.80% similarity compared with streptomyces samsunensis m1463(t). chemical investigation led to the isolation of three macrolides, efomycins m (1), g (2) and oxohygrolidin (3), along with two polyethers, abierixin (4) and 29-o-methylabierixin (5). to our knowledge, this is the firs ...201626809052
operon prediction using chaos embedded particle swarm optimization.operons contain valuable information for drug design and determining protein functions. genes within an operon are co-transcribed to a single-strand mrna and must be coregulated. the identification of operons is, thus, critical for a detailed understanding of the gene regulations. however, currently used experimental methods for operon detection are generally difficult to implement and time consuming. in this paper, we propose a chaotic binary particle swarm optimization (cbpso) to predict opero ...201624384714
co-circulation of plasmodium and bacterial dnas in blood of febrile and afebrile children from urban and rural areas in gabon.malaria is considered to be the most common etiology of fever in sub-saharan africa while bacteremias exist but are under assessed. this study aimed to assess bacteremias and malaria in children from urban and rural areas in gabon. dna extracts from blood samples of 410 febrile and 60 afebrile children were analyzed using quantitative polymerase chain reaction. plasmodium spp. was the microorganism most frequently detected in febrile (78.8%, 323/410) and afebrile (13.3%, 8/60) children, (p < 0.0 ...201627114297
pattern, clinical characteristics, and outcome of meningitis among hiv-infected adults admitted in a tertiary hospital in north western tanzania: a cross-sectional study.background. limited information exists on the etiologies, clinical characteristics, and outcomes of meningitis among hiv-infected patients in africa. we conducted a study to determine the etiology, clinical characteristics, and outcomes of meningitis among hiv-infected adults. methods. a prospective cross-sectional hospital based study was conducted among hiv-infected patients aged ≥18 years admitted to the medical wards with symptoms and signs of meningitis. sociodemographic and clinical inform ...201627651801
etiology and clinical features of 229 cases of bloodstream infection among chinese hiv/aids patients: a retrospective cross-sectional study.bloodstream infections (bsis) are prevalent among people living with hiv/aids. the etiology varies in different regions and different periods. we aimed to survey the etiological and clinical features of bsis in hiv patients in mainland china. we assessed all hiv patients with a positive blood culture in a chinese teaching hospital from september 2009 through december 2014. we excluded those with specimens likely to have been contaminated. we used pearson's chi-squared test to measure the differe ...201627502930
simultaneous detection of five pathogens from cerebrospinal fluid specimens using luminex technology.early diagnosis and treatment are crucial for the outcome of central nervous system (cns) infections. in this study, we developed a multiplex pcr-luminex assay for the simultaneous detection of five major pathogens, including mycobacterium tuberculosis, cryptococcus neoformans, streptococcus pneumoniae, and herpes simplex virus types 1 and 2, which frequently cause cns infections. through the hybridization reaction between multiplex pcr-amplified targets and oligonucleotide "anti-tag" sequences, ...201626861363
interleukin-17 mediated differences in the pathogenesis of hiv-1-associated tuberculous and cryptococcal meningitis.mycobacterium tuberculosis and cryptococcus neoformans are major causes of meningitis in hiv-1-infected patients. identifying differences in the inflammatory profiles of hiv-1-associated tuberculous meningitis (tbm) and cryptococcal meningitis may inform differences in immunopathogenic mechanisms in these diseases. in this study we compared the clinical and inflammatory features of hiv-1-associated tbm, and cryptococcal meningitis.201626765934
[chronic salmonella typhimurium diarrhea in an immunocompetent patient].chronic diarrhea caused by infection in immunocompetent patients is an infrequent condition in developed countries, although certain pathogens,generally parasites (giardia lamblia, isospora belli,cryptosporidium, cyclospora, strongyloides, ameba,trichuris and schistosoma) and some bacteria (aeromonas,plesiomonas, campylobacter, clostridium difficile, salmonella or mycobacterium tuberculosis)can cause persistent diarrhea.we present the case of a patient who showed salmonella typhimurium in his st ...201627125610
impact of lytr-cpsa-psr proteins on cell wall biosynthesis in corynebacterium glutamicum.proteins of the lcp (lytr, cpsa, psr) family have been shown to inherit important roles in bacterial cell wall biosynthesis. however, their exact function in the formation of the complex cell wall structures of the corynebacteriales, including the prominent pathogens mycobacterium tuberculosis and corynebacterium diphtheriae, remains unclear. here, we analyzed the role of the lcp proteins lcpa and lcpb of corynebacterium glutamicum, both of which localize at regions of nascent cell wall biosynth ...201627551018
genetics and genomics of the genus amycolatopsis.actinobacteria are gram-positive filamentous bacteria which contains some of the most deadly human pathogens (mycobacterium tuberculosis, m. leprae, corynebacterium diphtheriae, nocardia farcinica), plant pathogens (streptomyces scabies, leifsonia xyli) along with organisms that produces antibiotic (streptomycetes, amycolatopsis, salinospora). interestingly, these bacteria are equipped with an extraordinary capability of producing antibiotics and other metabolites which have medicinal properties ...201627407288
deploying aptameric sensing technology for rapid pandemic monitoring.the genome of virulent strains may possess the ability to mutate by means of antigenic shift and/or antigenic drift as well as being resistant to antibiotics with time. the outbreak and spread of these virulent diseases including avian influenza (h1n1), severe acute respiratory syndrome (sars-corona virus), cholera (vibrio cholera), tuberculosis (mycobacterium tuberculosis), ebola hemorrhagic fever (ebola virus) and aids (hiv-1) necessitate urgent attention to develop diagnostic protocols and as ...201626381238
structure-based design of inhibitors of the crucial cysteine biosynthetic pathway enzyme o-acetyl serine sulfhydrylase.the cysteine biosynthetic pathway is of fundamental importance for the growth, survival, and pathogenicity of the many pathogens. this pathway is present in many species but is absent in mammals. the ability of pathogens to counteract the oxidative defences of a host is critical for the survival of these pathogens during their long latent phases, especially in anaerobic pathogens such as entamoeba histolytica, leishmania donovani, trichomonas vaginalis, and salmonella typhimurium. all of these o ...201626303427
a quasi-universal medium to break the aerobic/anaerobic bacterial culture dichotomy in clinical microbiology.in the mid-19th century, the dichotomy between aerobic and anaerobic bacteria was introduced. nevertheless, the aerobic growth of strictly anaerobic bacterial species such as ruminococcus gnavus and fusobacterium necrophorum, in a culture medium containing antioxidants, was recently demonstrated. we tested aerobically the culture of 623 bacterial strains from 276 bacterial species including 82 strictly anaerobic, 154 facultative anaerobic, 31 aerobic and nine microaerophilic bacterial species as ...201626577141
evaluation of pulmonary microsporidiosis in iatrogenically immunosuppressed patients.microsporidia spp. are ubiquitous and infect a wide variety of intervertebrates and vertebrates, including humans. pulmonary microsporidiosis, characterized by nonspecific symptoms like fever, cough and dyspnea, is often overlooked in the differential diagnosis of pulmonary infections in immunsupressed patients. in this study, we aimed to determine the prevalence of pulmonary microsporidiosis in iatrogenically immunosuppressed patients and to evaluate the patient characteristics.201627266280
development of point-of-care testing for disaster-related infectious diseases.after disaster, the victims lose their safe lives and are even exposed to nature where they could suffer from animal bites and vectors followed by suffering from zoonosis or vector-born diseases. because of the urgent need for rapid and cheap diagnosis for infectious diseases after disaster, anonymous questionnaire clarified that leptospirosis, dengue, diarrhea, and cholera were recognized as common disaster-related infections in the philippines, while diarrhea and pneumonia were more common in ...201627020774
mce4a protein of mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a tnf-α dependent manner.mycobacterium tuberculosis subverts the host immune response through numerous immune-evasion strategies. apoptosis has been identified as one such mechanism and has been well studied in m. tuberculosis infection. here, we demonstrate that the mce4a protein of mce4 operon is involved in the induction of host cell apoptosis. earlier we have shown that the mce4a was required for the invasion and survival of m. tuberculosis. in this report we present evidence to establish a role for mce4a in the mod ...201627592091
high cell density production of multimethyl-branched long-chain esters in escherichia coli and determination of their physicochemical properties.microbial synthesis of oleochemicals derived from native fatty acid (fa) metabolism has presented significant advances in recent years. even so, native fa biosynthetic pathways often provide a narrow variety of usually linear hydrocarbons, thus yielding end products with limited structural diversity. to overcome this limitation, we took advantage of a polyketide synthase-based system from mycobacterium tuberculosis and developed an escherichia coli platform with the capacity to synthesize multim ...201627757170
immunogencity of antigens from mycobacterium tuberculosis self-assembled as particulate vaccines.traditional approaches to vaccine development have failed to identify better vaccines to replace or supplement bcg for the control of tuberculosis (tb). subunit vaccines offer a safer and more reproducible alternative for the prevention of diseases. in this study, the immunogenicity of bacterially derived polyester beads displaying three different rv antigens of mycobacterium tuberculosis was evaluated. polyester beads displaying the antigens rv1626, rv2032, rv1789, respectively, were produced i ...201627756533
nanomechanical properties of mscl alpha helices: a steered molecular dynamics study.gating of mechanosentive (ms) channels is driven by a hierarchical cascade of movements and deformations of transmembrane helices in response to bilayer tension. determining the intrinsic mechanical properties of the individual transmembrane helices is therefore central to understanding the intricacies of the gating mechanism of ms channels. we used a constant-force steered molecular dynamics (smd) approach to perform unidirectional pulling tests on all the helices of mscl in m. tuberculosis and ...201627753526
functional studies of five toxin-antitoxin modules in mycobacterium tuberculosis h37rv.toxin-antitoxin (ta) systems, which consist of an intracellular toxin and its antidote (antitoxin), are encoded by ubiquitous genetic modules in prokaryotes. commonly, the activity of a toxin is inhibited by its antitoxin under normal growth conditions. however, antitoxins are degraded in response to environmental stress, and toxins liberated from antitoxins consequently induce cell death or growth arrest. in free-living prokaryotes, ta systems are often present in large numbers and are consider ...201628066388
effects of mycobacterium tuberculosis esat6-cfp10 protein on cell viability and production of nitric oxide in alveolar macrophages.mycobacterium tuberculosis is the major pathogen of tuberculosis, which affects approximately one-third of the world's population. the 6 kda early secreted antigenic target (esat6) and the 10 kda culture filtrate protein (cfp10), which are secreted by the esx-1 system in m. tuberculosis, can contribute to mycobacterial virulence.201627635210
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