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differential roles of iron storage proteins in maintaining the iron homeostasis in mycobacterium tuberculosis.ferritins and bacterioferritins are iron storage proteins that represent key players in iron homeostasis. several organisms possess both forms of ferritins, however, their relative physiological roles are less understood. mycobacterium tuberculosis possesses both ferritin (bfrb) and bacterioferritin (bfra), playing an essential role in its pathogenesis as reported by us earlier. this study provides insights into the role of these two proteins in iron homeostasis by employing m. tuberculosis bfr ...201728060867
novel bacterial topoisomerase inhibitors with potent broad-spectrum activity against drug-resistant bacteria.the novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of dna gyrase and topoisomerase iv that do not have cross-resistance with the quinolones. here, we report the evaluation of the in vitro properties of a new series of this type of small molecules. exemplar compounds selectively and potently inhibited the catalytic activities of escherichia coli dna gyrase and topoisomerase iv but did not block the dna breakage-reunion step. compounds showed br ...201728223393
the antibacterial activities of aditoprim and its efficacy in the treatment of swine streptococcosis.aditoprim (adp) has potential use as an antimicrobial agent in animals. however, its pharmacodynamic properties have not been systematically studied yet. in this study, the in vitro antibacterial activities of adp and its main metabolites were assayed, and the in vivo antibacterial efficacy of adp for the treatment of swine streptococcosis was evaluated. it was shown that salmonella and streptococcus from swine, escherichia coli and salmonella from chickens, e. coli, streptococcus, mannheimia, p ...201728145487
pathogenic mechanisms of intracellular bacteria.we wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread.201728134679
the role of universal stress proteins in bacterial infections.universal stress proteins are ubiquitously expressed in bacteria, archaea and plants and other eukaryotes. a general property of usps is their role in adaptation of bacteria to oxidative stress, high temperature, low ph and/or hypoxia. there is increasing evidence that these proteins facilitate the adaption of bacterial pathogens to the human host environment, thereby facilitating colonisation and pathogenicity. usps in mycobacterium tuberculosis are well studied and may play a role in latency o ...201728120710
refugees and antimicrobial resistance: a systematic review.there is a large increase in the numbers of refugees and asylum seekers worldwide and a lack of data on the carriage of antimicrobial resistance in refugee/asylum seeking groups.201727919742
reoxidation of the thiol-disulfide oxidoreductase mdba by a bacterial vitamin k epoxide reductase in the biofilm-forming actinobacterium actinomyces oris.post-translocational protein folding in the gram-positive biofilm-forming actinobacterium actinomyces oris is mediated by a membrane-bound thiol-disulfide oxidoreductase named mdba, which catalyzes oxidative folding of nascent polypeptides transported by the sec translocon. reoxidation of mdba involves a bacterial vitamin k epoxide reductase (vkor)-like protein that contains four cysteine residues c93/c101 and c175/c178 with the latter forming a canonical cxxc thioredoxin-like motif; however, th ...201728289087
rational design of reversible inhibitors for trehalose 6-phosphate phosphatases.in some organisms, environmental stress triggers trehalose biosynthesis that is catalyzed collectively by trehalose 6-phosphate synthase, and trehalose 6-phosphate phosphatase (t6pp). t6pp catalyzes the hydrolysis of trehalose 6-phosphate (t6p) to trehalose and inorganic phosphate and is a promising target for the development of antibacterial, antifungal and antihelminthic therapeutics. herein, we report the design, synthesis and evaluation of a library of aryl d-glucopyranoside 6-sulfates to se ...201728192710
chemical characteristics, antimicrobial and cytotoxic activities of the essential oil of egyptian cinnamomum glanduliferum bark.the essential oil isolated from the bark of cinnamomum glanduliferum (wall) meissn that grown in egypt was screened for the first time. the chemical composition was analyzed by gc and gc/mass. the antimicrobial activity of the oil was assessed using agar-well diffusion method toward representatives for each of gram-positive bacteria, gram-negative bacteria, and fungi. the cytotoxic activity was checked using three human cancer cell lines. twenty seven compounds were identified, representing 99.0 ...201728190283
development of antibacterial conjugates using sulfamethoxazole with monocyclic terpenes: a systematic medicinal chemistry based computational approach.to develop 6 conjugate agents of the moribund antibiotic sulfamethoxazole (smz) joined to 6 individual monoterpenes, followed by protocols of medicinal chemistry as potent antibacterials, against multidrug resistant (mdr) human gruesome pathogenic bacteria.201728254074
bacterial virulence factors: secreted for survival.virulence is described as an ability of an organism to infect the host and cause a disease. virulence factors are the molecules that assist the bacterium colonize the host at the cellular level. these factors are either secretory, membrane associated or cytosolic in nature. the cytosolic factors facilitate the bacterium to undergo quick adaptive-metabolic, physiological and morphological shifts. the membrane associated virulence factors aid the bacterium in adhesion and evasion of the host cell. ...201728148975
model systems for pulmonary infectious diseases: paradigms of anthrax and tuberculosis.robert koch utilized animal model systems to put forward his postulates while discovering the etiological agents of anthrax and tuberculosis, bacillus anthracis and mycobacterium tuberculosis, respectively. after more than 130 years, we have achieved limited success towards understanding these two pestilences, which have propagated as scourge against humans. b. anthracis and m. tuberculosis are diverse organisms, which share a common evolutionary path in tropics. they adapt unique strategies to ...201728137237
facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions.recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. at the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. using such models, hypo ...201726857943
antimycobacterial, antimicrobial activity, experimental (ft-ir, ft-raman, nmr, uv-vis, dsc) and dft (transition state, chemical reactivity, nbo, nlo) studies on pyrrole-isonicotinyl hydrazine.as part of a study of pyrrole hydrazone, we have investigated quantum chemical calculations, molecular geometry, relative energy, vibrational properties and antimycobacterial/antimicrobial activity of pyrrole-2-carboxaldehyde isonicotinyl hydrazone (pcinh), by applying the density functional theory (dft) and hartree fock (hf). good reproduction of experimental values is obtained and with small percentage error in majority of the cases in comparison to theoretical result (dft). the experimental f ...201728213139
an efficient system for deletion of large dna fragments in escherichia coli via introduction of both cas9 and the non-homologous end joining system from mycobacterium smegmatis.accompanied with the internal non-homologous end joining (nhej) system, cas9 can be used to easily inactivate a gene or delete a fragment through introduction of dna double-stranded breaks (dsbs) in eukaryotic cells. while in most prokaryotes (e.g. escherichia coli), due to the lack of nhej, homologous recombination (hr) is required for repair of dsbs, which is less convenient. here, a markerless system was developed for rapid gene inactivation or fragment deletion in e. coli via introduction of ...201728257845
madurastatin b3, a rare aziridine derivative from actinomycete nocardiopsis sp. ls150010 with potent anti-tuberculosis activity.since the discovery of the first antibiotic, natural products have played an important role in chemistry, biology and medicine. to explore the potential of bioactive compounds from microbes isolated from the southeast of tibet, china, a crude extract library was constructed and screened against staphylococcus aureus. the strain nocardiopsis sp. ls150010 was scaled up and subjected to further chemical studies, resulting in the identification of n-salicyloyl-2-aminopropan-1,3-diol (2) and its rare ...201728181080
usefulness of lymphoid granulomatous inflammation culture obtained by endobronchial ultrasound-guided transbronchial needle aspiration in a fungal endemic area.endobronchial ultrasound-guided transbronchial needle aspiration (ebus-tbna) is the procedure of choice for the evaluation of mediastinal/hilar lymph node enlargements. granulomatous inflammation of the mediastinal/hilar lymph nodes is often identified on routine histology. in addition, mediastinal lymphadenopathy may be present with undiagnosed infection. we sought to determine the usefulness of routine cultures and histology for infectious etiologies in a fungal endemic area when granulomatous ...201727503156
drivers of airborne human-to-human pathogen transmission.airborne pathogens - either transmitted via aerosol or droplets - include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza a viruses, mycobacterium tuberculosis, streptococcus pneumoniae, and bordetella pertussis. emerging zoonotic pathogens, for example, mers coronavirus, avian influenza viruses, coxiella, and francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. here, we synthesize in ...201727918958
antibiotic capture by bacterial lipocalins uncovers an extracellular mechanism of intrinsic antibiotic resistance.the potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. here we show that a soluble bacterial lipocalin produced by burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo these phenotypes were recapitulated by heterologous expression in b. cenocepacia of lipocalin genes from pseudomonas aeruginosa, mycobacterium tuberculosis, and methici ...201728292982
novel quinoxalinyl chalcone hybrid scaffolds as enoyl acp reductase inhibitors: synthesis, molecular docking and biological evaluation.we report herein, first ever synthesis of series of novel differently substituted quinoxalinyl chalcones using claisen schmidt condensation, its molecular docking studies, and potential to be good anti-microbial, anti-tubercular and anti-cancer agents. the antimicrobial studies were carried out against staphylococcus aureus, escherichia coli and candida albicans using disc diffusion procedure. the selected chalcones were tested for anti-cancer and cytotoxicity activity against mcf-7 cancer cell ...201728372908
chemical characterization and evaluation of antibacterial, antifungal, antimycobacterial, and cytotoxic activities of talinum paniculatum.in this study, the bioactivity of talinum paniculatum was evaluated, a plant widely used in folk medicine. the extract from the t. paniculatum leaves (le) was obtained by percolation with ethanol-water and then subjecting it to liquid-liquid partitions, yielding hexane (hx), ethyl acetate (etoac), butanol (buoh), and aqueous (aq) fractions. screening for antimicrobial activity of the le and its fractions was evaluated in vitro through broth microdilution method, against thirteen pathogenic and n ...201726603226
antimicrobial and cytotoxicity properties of the organic solvent fractions of clerodendrum myricoides (hochst.) r. br. ex vatke: kenyan traditional medicinal plant.clerodendrum myricoides is a kenyan herbal plant used in the management of respiratory diseases. in the current study, we investigated in vitro antimicrobial activity, cytotoxicity, and phytochemical screening of c. myricoides.201727366347
prospective etiological investigation of community-acquired pulmonary infections in hospitalized people living with hiv.the study of the etiological agents of community-acquired pulmonary infections is important to guide empirical therapy, requires constant updating, and has a substantial impact on the prognosis of patients. the objective of this study is to determine prospectively the etiology of community-acquired pulmonary infections in hospitalized adults living with hiv. patients were submitted to an extended microbiological investigation that included molecular methods. the microbiological findings were eva ...201728121925
peptide 19 of porphyromonas gingivalis heat shock protein is a potent inducer of low-density lipoprotein oxidation.although periodontal pathogens show a strong association with development of atherosclerosis, little is known about how a microorganism contributes to disease onset and progression. oxidation of low-density lipoprotein (ldl) is a major risk factor of atherogenesis. the principal objective of this study is to evaluate the ability of peptide 19 (pep19) of porphyromonas gingivalis (pg) heat shock protein (hsp) as a potent inducer of ldl oxidation, and a secondary objective is to compare this abilit ...201727712463
establishment of multiplex solid-phase strip pcr test for detection of 24 ocular infectious disease pathogens.to establish and evaluate a new multiplex solid-phase strip polymerase chain reaction (strip pcr) for concurrent detection of common ocular infectious disease pathogens.201728282487
the antibiotic resistance crisis, with a focus on the united states.beginning with the discovery of penicillin by alexander fleming in the late 1920s, antibiotics have revolutionized the field of medicine. they have saved millions of lives each year, alleviated pain and suffering, and have even been used prophylactically for the prevention of infectious diseases. however, we have now reached a crisis where many antibiotics are no longer effective against even the simplest infections. such infections often result in an increased number of hospitalizations, more t ...201728246379
"infectious supercarelessness" in discussing antibiotic-resistant bacteria.many bacterial pathogens are exhibiting resistance to increasing numbers of antibiotics making it much more challenging to treat the infections caused by these microbes. in many reports in the media and perhaps even in discussions among physicians and biomedical scientists, these bacteria are frequently referred to as "bugs" with the prefix "super" appended. this terminology has a high potential to elicit unjustified inferences and fails to highlight the broader evolutionary context. understandi ...201728174759
comparing galactan biosynthesis in mycobacterium tuberculosis and corynebacterium diphtheriae.the suborder corynebacterineae encompasses species like corynebacterium glutamicum, which has been harnessed for industrial production of amino acids, as well as corynebacterium diphtheriae and mycobacterium tuberculosis, which cause devastating human diseases. a distinctive component of the corynebacterineae cell envelope is the mycolyl-arabinogalactan (mag) complex. the mag is composed of lipid mycolic acids, and arabinofuranose (araf) and galactofuranose (galf) carbohydrate residues. elucidat ...201728039359
infections of the central nervous system after unrelated donor umbilical cord blood transplantation or human leukocyte antigen-matched sibling transplantation.we analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (cns) infections in consecutive patients with receiving umbilical cord blood transplantation (ucbt) (n = 343) or hla-matched sibling donor stem cell transplantation (mst) (n = 366). thirty-four cns infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). the cumulative incidence (ci) risk of developing a cns infection was .6% at day +30, 2.3% at ...201727794456
strong anti-epstein barr virus (ebv) or cytomegalovirus (cmv) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy.intact immune responses to cytomegalovirus (cmv) and epstein-barr virus (ebv) represent a biologically and clinically relevant correlate of 'immunological fitness' in humans. however, there is a lack of knowledge concerning anti-ebv or anti-cmv responses in patients with pulmonary tuberculosis (tb), in whom aberrant immune responses may promote progression of clinical disease.201728193504
mycobacterium marinum degrades both triacylglycerols and phospholipids from its dictyostelium host to synthesise its own triacylglycerols and generate lipid inclusions.during a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (fas) and sterols are the major energy and carbon source for mycobacterium tuberculosis. mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. lipid droplets (lds) store fas in form of triacylglycerols (tags) and are energy reservoirs of prokaryotes and eukaryotes. using the dictyostelium discoideum/mycobacterium marinum infection m ...201728103313
design and use of mouse control dna for dna biomarker extraction and pcr detection from urine: application for transrenal mycobacterium tuberculosis dna detection.urine samples are increasingly used for diagnosing infections including escherichia coli, ebola virus, and zika virus. however, extraction and concentration of nucleic acid biomarkers from urine is necessary for many molecular detection strategies such as polymerase chain reaction (pcr). since urine samples typically have large volumes with dilute biomarker concentrations making them prone to false negatives, another impediment for urine-based diagnostics is the establishment of appropriate cont ...201728285168
modified vaccinia virus ankara: history, value in basic research, and current perspectives for vaccine development.safety tested modified vaccinia virus ankara (mva) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. historically, mva was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. adapted to growth in avian cells mva lost the ability ...201728057259
impact of infectious disease epidemics on tuberculosis diagnostic, management, and prevention services: experiences and lessons from the 2014-2015 ebola virus disease outbreak in west africa.the world health organization (who) global tuberculosis report 2015 states that 28% of the world's 9.6 million new tuberculosis (tb) cases are in the who africa region. the mano river union (mru) countries of west africa-guinea, sierra leone, and liberia-have made incremental sustained investments into tb control programmes over the past two decades. the devastating ebola virus disease (evd) outbreak of 2014-2015 in west africa impacted significantly on all sectors of the healthcare systems in t ...201727818362
synthesis of novel pyrazinamide derivatives based on 3-chloropyrazine-2-carboxamide and their antimicrobial evaluation.aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. four compounds possessed in vitro whole cell activity against mycobacterium tuberculosis h37rv that was at least equivalent to that of the standard pyrazinamide. mic values ranged from 6 to 42 μm. the best mic (6 μm) was displayed by 3-[(4-methylbenzyl)amino]pyrazine-2-carboxamide (8) that also showed low cytotoxicity in the hepg2 cell li ...201728157178
production and characterization of a highly pure rna polymerase holoenzyme from mycobacterium tuberculosis.recent publications have shown that active rna polymerase (rnap) from mycobacterium tuberculosis (mtbrnap) can be produced by expressing all four subunits in a single recombinant escherichia coli strain [1-3]. by reducing the number of plasmids and changing the codon usage of the mtb genes in the co-expression system published by banerjee et al. [1], we present a simplified, detailed and reproducible protocol for the purification of recombinant mtbrnap containing the ω subunit. moreover, we desc ...201728323168
the structure and function of mycobacterium tuberculosis mazf-mt6 provides insights into conserved features of mazf endonucleases.toxin-antitoxin systems are ubiquitous in prokaryotic and archaea genomes and regulate growth in response to stress. e. coli contains at least 36 putative toxin-antitoxin gene pairs, and some pathogens such as mycobacterium tuberculosis (mtb) have over 90 toxin-antitoxin operons. e. coli mazf cleaves free mrna after encountering stress and nine mtb mazf family members cleave mrna, trna, or rrna. moreover, mtb mazf-mt6 cleaves 23s rrna helix 70 to inhibit protein synthesis. the overall tertiary f ...201728298445
comparative analyses of selection operating on non-translated intergenic regions of diverse bacterial species.non-translated intergenic regions (igrs) comprise 10-15% of bacterial genomes, and contain many regulatory elements with key functions. despite this, there are few systematic studies on the strength and direction of selection operating on igrs in bacteria using whole genome sequence datasets. here we exploit representative whole genome datasets from six diverse bacterial species; staphylococcus aureus, streptococcus pneumoniae, mycobacterium tuberculosis, salmonella enterica, klebsiella pneumoni ...201728280056
mycobacterium tuberculosis rv1474c is a tetr-like transcriptional repressor that regulates aconitase, an essential enzyme and rna-binding protein, in an iron-responsive manner.mycobacterium tuberculosis (m.tb), tuberculosis (tb) causing bacteria, employs several mechanisms to maintain iron homeostasis which is critical for its survival and pathogenesis. m.tb aconitase (acn), a [4fe-4s] cluster-containing essential protein, apart from participating in energy cycle, also binds to predicted iron-responsive rna elements. in this study, we identified rv1474c as a regulator of its operonic partner acn and carried out its biochemical and functional characterization. the bind ...201728237036
msmeg_5684 down-regulation in mycobacterium smegmatis affects its permeability, survival under stress and persistence.the mycobacterium tuberculosis (mtb) genome sequence and annotation details have been available for a long time; however physiological relevance of many orfs remains poorly described. mtb is a pathogenic strain; hence, surrogate strains such as mycobacterium bovis bcg and mycobacterium smegmatis (msmeg) have also been studied to gain an understanding of mycobacterial physiology and metabolism. the mycobacterium smegmatis mc(2) 155 orf msmeg_5684 is annotated as a part of serine biosynthetic path ...201728237035
new nitrofurans amenable by isocyanide multicomponent chemistry are active against multidrug-resistant and poly-resistant mycobacterium tuberculosis.a set of structurally diverse n-amino δ-lactams decorated with a 5-nitro-2-furyl moiety was synthesized using isocyanide-based multicomponent chemistry and evaluated for antibacterial activity. three compounds displayed a selective and potent (mic 22-33μm) inhibition of m. tuberculosis h37rv strain growth, while other gram-positive (mrsa and e. faecium) or gram-negative (e. coli, p. aeruginosa, a. baumannii, k. pneumoniae) pathogens were not affected. the compounds also displayed moderate-low cy ...201728214232
structure and variation of crispr and crispr-flanking regions in deleted-direct repeat region mycobacterium tuberculosis complex strains.crispr and crispr-flanking genomic regions are important for molecular epidemiology of mycobacterium tuberculosis complex (mtbc) strains, and potentially for adaptive immunity to phage and plasmid dna, and endogenous roles in the bacterium. genotyping in the israel national mycobacterium reference center tel-aviv of over 1500 mtbc strains from 2008-2013 showed three strains with validated negative 43-spacer spoligotypes, that is, with putatively deleted direct repeat regions (deleted-dr/crispr r ...201728201993
ca(2+)-dependent focal exocytosis of golgi-derived vesicles helps phagocytic uptake in macrophages.the role of golgi apparatus during phagocytic uptake by macrophages has been ruled out in the past. notably, all such reports were limited to fcγ receptor-mediated phagocytosis. here, we unravel a highly devolved mechanism for recruitment of golgi-derived secretory vesicles during phagosome biogenesis, which was important for uptake of most cargos, except the igg-coated ones. we report recruitment of mannosidase-ii-positive golgi-derived vesicles during uptake of diverse targets, including latex ...201728174296
characterization and function of mycobacterium tuberculosis h37rv lipase rv1076 (lipu).lipids and lipases/esterases are essential for mycobacterium tuberculosis (mtb) survival and persistence, even virulence. mycobacterium tuberculosis h37rv rv1076 (lipu), a member of lipase family, is homologous to the human hormone sensitive lipase (hsl) based on the presence of conserved motif 'gxsxg'. to define the enzymatic characteristics of rv1076, the gene was cloned, and expressed in escherichia coli. the protein was purified for enzymatic characterization. lipu showed high specific activ ...201728164792
rv0774c, an iron stress inducible, extracellular esterase is involved in immune-suppression associated with altered cytokine and tlr2 expression.tuberculosis, one of the leading cause of death from infectious diseases, is caused by mycobacterium tuberculosis. the genome of m. tuberculosis has been sequenced and nearly 40% of the whole genome sequence was categorized as hypothetical. rv0774c was annotated as membrane exported hypothetical protein in tb database. in silico analysis revealed that rv0774c is a paralog of pe-pgrs multi gene family with 100 aa n-terminal domain similar to pe domain of pe-pgrs proteins. its c-terminal domain is ...201728161108
role of reactive oxygen species (ros) in therapeutics and drug resistance in cancer and bacteria.evading persistent drug resistance in cancer and bacteria is quintessential to restore health in humans, and impels intervention strategies. a distinct property of the cancer phenotype is enhanced glucose metabolism and oxidative stress. reactive oxygen species (ros) are metabolic byproducts of aerobic respiration and are responsible for maintaining redox homeostasis in cells. redox balance and oxidative stress are orchestrated by antioxidant enzymes, reduced thiols and nadp(h) cofactors, which ...201728135088
rhodococcus erythropolis as a host for expression, secretion and glycosylation of mycobacterium tuberculosis proteins.glycosylation is one of the most abundant posttranslational polypeptide chain modification in nature. although carbohydrate modification of protein antigens from many microbial pathogens constitutes important components of b cell epitopes, the role in t cell immunity is not completely understood. there is growing evidence about the importance of these modifications in host bacteria interactions in tuberculosis. it is known, that the sugars present in some mycobacterium tuberculosis glycoproteins ...201728103877
engineering mycobacteria for the production of self-assembling biopolyesters displaying mycobacterial antigens for use as a tuberculosis vaccine.tuberculosis (tb) is a disease caused by mycobacterium tuberculosis or mycobacterium bovis and still remains one of the world's biggest global health burdens. recently, engineered polyhydroxyalkanoate (pha) biobeads that were produced in both escherichia coli and lactococcus lactis and displayed mycobacterial antigens were found to induce significant cell-mediated immune responses in mice. we observed that such pha beads contained host cell proteins as impurities, which we hypothesized to have t ...201728087528
anti-folates potentiate bactericidal effects of other antimicrobial agents.synergies between sulfonamides and other antimicrobial agents have long been reported, but the reason still remains unclear. previously, vilchèze et al. found that, sulfamethoxazole (smx) could potentiate the bacterialcidal activity of isoniazid (inh) and rifampin (rif) in mycobacterium tuberculosis. to test if this was also the case in other bacteria, the ability to potentiate bactericidal effect of rif by smx was evaluated in escherichia coli, staphylococcus aureus, salmonella typhimurium and ...201728074051
antiprotozoal, antimycobacterial, and anti-inflammatory evaluation of cnidoscolus chayamansa (mc vaugh) extract and the isolated compounds.cnidoscolus chayamansa is a medicinal and edible plant known as chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. in this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the chcl3:meoh (1:1) leaves extract and isolat ...201728222400
mycobacterium tuberculosis rv0560c is not essential for growth in vitro or in macrophages.mycobacterium tuberculosis rv0560c, a putative benzoquinone methyl transferase, is heavily induced in response to salicylate exposure. it has some similarity to escherichia coli ubig, although its role in ubiquinone or menaquinone synthesis is not clear, since m. tuberculosis is not known to produce ubiquinone. we constructed an unmarked in-frame deletion of rv0560c in m. tuberculosis to determine its role in vitro. deletion of rv0560c in m. tuberculosis had no effect on growth in medium contain ...201728061949
structure and interactions of reca: plasticity revealed by molecular dynamics simulations.eleven independent simulations, each involving three consecutive molecules in the reca filament, carried out on the protein from mycobacterium tuberculosis, mycobacterium smegmatis and escherichia coli and their adenosine triphosphate (atp) complexes, provide valuable information which is complementary to that obtained from crystal structures, in addition to confirming the robust common structural framework within which reca molecules from different eubacteria function. functionally important lo ...201728049371
inhibition of β-lactamases of mycobacteria by avibactam and clavulanate.mycobacterium tuberculosis and mycobacterium abscessus produce broad-spectrum class a β-lactamases, blac and bla mab , which are inhibited by clavulanate and avibactam, respectively. blac differs from bla mab at ambler position 132 in the conserved motif sdn (sdg versus sdn, respectively). here, we investigated whether this polymorphism could account for the inhibition specificity of β-lactamases from slowly and rapidly growing mycobacteria.201728039278
novel chemical scaffolds for inhibition of rifamycin-resistant rna polymerase discovered from high-throughput screening.rifampin has been a cornerstone of tuberculosis (tb) treatment since its introduction. the rise of multidrug-resistant and extensively drug-resistant tb makes the development of novel therapeutics effective against these strains an urgent need. site-specific mutations in the target enzyme of rifampin, rna polymerase (rnap) comprises the majority (~97%) of rifamycin-resistant (rif(r)) strains of mycobacterium tuberculosis (mtb). to identify novel inhibitors of bacterial rnap, an in vitro plasmid- ...201728027449
structural basis for rifamycin resistance of bacterial rna polymerase by the three most clinically important rpob mutations found in mycobacterium tuberculosis.since 1967, rifampin (rmp, a rifamycin) has been used as a first line antibiotic treatment for tuberculosis (tb), and it remains the cornerstone of current short-term tb treatment. increased occurrence of rifamycin-resistant (rif(r) ) tb, ∼41% of which results from the rpob s531l mutation in rna polymerase (rnap), has become a growing problem worldwide. in this study, we determined the x-ray crystal structures of the escherichia coli rnaps containing the most clinically important s531l mutation ...201728009073
intrinsic rifamycin resistance of mycobacterium abscessus is mediated by adp-ribosyltransferase mab_0591.rifampicin, a potent first-line tb drug of the rifamycin group, shows only little activity against the emerging pathogen mycobacterium abscessus. reportedly, bacterial resistance to rifampicin is associated with polymorphisms in the target gene rpob or the presence of enzymes that modify and thereby inactivate rifampicin. the aim of this study was to investigate the role of the mab_0591 (arrmab)-encoded rifampicin adp-ribosyltransferase (arr_mab) in innate high-level rifampicin resistance in m. ...201727999011
high-throughput identification of dna-encoded igg ligands that distinguish active and latent mycobacterium tuberculosis infections.the circulating antibody repertoire encodes a patient's health status and pathogen exposure history, but identifying antibodies with diagnostic potential usually requires knowledge of the antigen(s). we previously circumvented this problem by screening libraries of bead-displayed small molecules against case and control serum samples to discover "epitope surrogates" (ligands of iggs enriched in the case sample). here, we describe an improved version of this technology that employs dna-encoded li ...201727957856
native esi mass spectrometry can help to avoid wrong interpretations from isothermal titration calorimetry in difficult situations.we studied by native esi-ms the binding of various dna-polymerase-derived peptides onto dna-polymerase processivity rings from escherichia coli, pseudomonas aeruginosa, and mycobacterium tuberculosis. these homodimeric rings present two equivalent specific binding sites, which leads to successive formation during a titration experiment of singly- and doubly occupied rings. by using the esi-ms free-ring spectrum as a ruler, we derived by robust linear regression the fractions of the different rin ...201727957716
evolutionary adaptation of the essential trna methyltransferase trmd to the signaling molecule 3',5'-camp in bacteria.the nucleotide signaling molecule 3',5'-cyclic adenosine monophosphate (3',5'-camp) plays important physiological roles, ranging from carbon catabolite repression in bacteria to mediating the action of hormones in higher eukaryotes, including human. however, it remains unclear whether 3',5'-camp is universally present in the firmicutes group of bacteria. we hypothesized that searching for proteins that bind 3',5'-camp might provide new insight into this question. accordingly, we performed a geno ...201727881678
mycobacterium tuberculosis and mycobacterium marinum non-homologous end-joining proteins can function together to join dna ends in escherichia coli.mycobacterium tuberculosis and mycobacterium smegmatis express a ku protein and a dna ligase d and are able to repair dna double strand breaks (dsbs) by non-homologous end-joining (nhej). this pathway protects against dna damage when bacteria are in stationary phase. mycobacterium marinum is a member of this mycobacterium family and like m. tuberculosis is pathogenic. m. marinum lives in water, forms biofilms and infects fish and frogs. m. marinum is a biosafety level 2 (bsl2) organism as it can ...201727613236
functional characterization of hypothetical proteins of mycobacterium tuberculosis with possible esterase/lipase signature: a cumulative in silico and in vitro approach.the functional aspect of several mycobacterium proteins annotated as hypothetical are yet to be discovered. in the present investigation, in silico approaches were used to predict the biological function of some of the unknown mtb proteins, which were further validated by wet lab experiments. after screening thousands of mtb proteins, functionally unknown hypothetical proteins rv0421c, rv0519c, rv0774c, rv1191, rv1592c, and rv3591c were chosen on the basis of their importance in mtb life cycle. ...201727050490
a novel self-cleavable tag zbasic-∆i-cm and its application in the soluble expression of recombinant human interleukin-15 in escherichia coli.soluble expression of recombinant therapeutic proteins in escherichia coli (e. coli) has been a challenging task in biopharmaceutical development. in this study, a novel self-cleavable tag zbasic-intein has been constructed for the soluble expression and purification of a recombinant cytokine, human interleukin-15 (il-15). we screened several solubilizing tags fused with the self-cleavable mycobacterium tuberculosis reca mini-intein ∆i-cm and demonstrated that zbasic tag can significantly improv ...201727683210
consensus numbering system for the rifampicin resistance-associated rpob gene mutations in pathogenic mycobacteria.the rpob gene codes for the rna polymerase β subunit, which is the target of rifampicin, an essential drug in the treatment of tuberculosis and other mycobacterial infections. this gene is present in all bacteria, but its length and nucleotide sequence vary between bacterial species, including mycobacteria. mutations in the rpob gene alter the structure of this protein and cause drug resistance. to describe the resistance-associated mutations, the scientific and medical communities have been usi ...201727664776
fusion molecules of heat shock protein hspx with other antigens of mycobacterium tuberculosis show high potential in serodiagnosis of tuberculosis.variable individual response against the antigens of mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. antigens of m. tuberculosis hspx and pe35 were expressed in a soluble form whereas tnpsts1 and fbpc1 were expressed as inclusion bodies at 37°c. heat shock protein hspx when attached to the n ...201727654048
a systematic approach for developing bacteria-specific imaging tracers.the modern patient is increasingly susceptible to bacterial infections including those due to multidrug-resistant organisms (mdros). noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically.201727635025
mycobacterium tuberculosis rv1400c encodes functional lipase/esterase.lipases catalyze the hydrolysis of triglycerides (tag). open reading frames (orf) predicted to encode enzymes involved in fatty acids breakdown are abundant in mycobacterium tuberculosis genome. to define the function of m. tuberculosis rv1400c (lipi), a putative hormone sensitive lipase (hsl) subfamily orf, the rv1400c was cloned, expressed and purified in escherichia coli as fusion protein. the purified lipi preferred short carbon chain substrates with an optimal activity at 37 °c/ph 8.0 and s ...201727154903
efficacy of resistance to francisella imparted by ity/nramp/slc11a1 depends on route of infection.natural resistance-associated macrophage protein (nramp) encoded by the slc11a1 gene is a membrane-associated transporter of divalent metal ions. murine slc11a1 has two known alleles, a functional slc11a1(gly169), which is found in dba2/j, nod/ltj, and 129p3/j and related mouse strains, and a non-functional slc11a1(asp169), that is found in c56bl/6j (b6) and balb/cj mice. b6 mice congenic for slc11a1(gly169) (b6-slc11a1(g169) ) are markedly resistant to the intracellular pathogens salmonella, le ...201728360906
influence of socio-economic inequality measured by the gini coefficient on meningitis incidence caused by mycobacterium tuberculosis and haemophilus influenzae in colombia, 2008-2011.bacterial meningitis is an important cause of infectious neurological morbidity and mortality. its incidence has decreased with the introduction of vaccination programmes against preventable agents. however, low-income and middle-income countries with poor access to health care still have a significant burden of the disease. thus, the relationship between the gini coefficient and h. influenzae and m. tuberculosis meningitis incidence in colombia, during 2008-2011, was assessed. in this ecologica ...201728353449
discovery of anti-microbial and anti-tubercular molecules from fusarium solani: an endophyte of glycyrrhiza glabra.glycyrrhiza glabra is a high-value medicinal plant thriving in biodiversity rich kashmir himalaya. the present study was designed to explore the fungal endophytes from g. glabra as a source of bioactive molecules.201728150900
colonization with helicobacter is concomitant with modified gut microbiota and drastic failure of the immune control of mycobacterium tuberculosis.epidemiological and experimental observations suggest that chronic microbial colonization can impact the immune control of other unrelated pathogens contracted in a concomitant or sequential manner. possible interactions between mycobacterium tuberculosis infection and persistence of other bacteria have scarcely been investigated. here we demonstrated that natural colonization of the digestive tract with helicobacter hepaticus in mice is concomitant with modification of the gut microbiota, subcl ...201728145441
baseline hbv load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis.hepatitis associated anti-tuberculous treatment (hatt) has been a main obstacle in managing patients co-infected with mycobacterium tuberculosis and hepatitis b virus (hbv). therefore, we evaluated the factors related to the severity of adverse effects during hatt, especially those associated with liver failure. a retrospective study was carried out at tongji hospital from 2007 to 2012. increases in serum transaminase levels of >3, 5, and 10 times the upper limit of normal (uln) were used to def ...201728224437
crispr/cas9-the ultimate weapon to battle infectious diseases?infectious diseases are a leading cause of death worldwide. novel therapeutics are urgently required to treat multidrug-resistant organisms such as mycobacterium tuberculosis and to mitigate morbidity and mortality caused by acute infections such as malaria and dengue fever virus as well as chronic infections such as human immunodeficiency virus-1 and hepatitis b virus. the clustered regularly interspaced short palindromic repeats (crispr)/crispr-associated protein 9 (cas9) system, which has rev ...201727860197
mait cells are reduced in frequency and functionally impaired in human t lymphotropic virus type 1 infection: potential clinical implications.htlv-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition htlv-1-associated myelopathy/tropical spastic paraparesis (ham/tsp). it is unclear why a minority of infected subjects develop ham/tsp. the cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. furthermore, htlv-1-infected individuals have an increase inciden ...201728384290
mycobacterium tuberculosis infection among persons who inject drugs in san diego, california.persons who inject drugs (pwid) might be at increased risk for mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (ltbi) due to their injection drug use.201728284258
miliary tuberculosis infection during hepatitis c treatment with sofosbuvir and ledipasvir plus ribavirin.chronic hepatitis c virus (hcv) infection is one of the main causes of chronic liver disease worldwide. in the last 5 years, treatment for hcv infection has experienced a marked development. in 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. however, new side effects have been associated. we report the first case of an hcv infected patient treated for 12 wk with the comb ...201728217253
epidemiology of infectious encephalitis causes in 2016.we performed a literature search in the medline database, using the pubmed website. the incidence of presumably infectious encephalitis is estimated at 1.5-7 cases/100,000 inhabitants/year, excluding epidemics. infectious encephalitis and immune-mediated encephalitis share similar clinical signs and symptoms. the latter accounts for a significant proportion of presumably infectious encephalitis cases without any established etiological diagnosis; as shown from a prospective cohort study where 21 ...201728341533
management of adult infectious encephalitis in metropolitan france.infectious encephalitis is a severe disease leading to a high mortality and morbidity. the most frequent causes include herpes simplex virus, varicella zoster virus, listeria monocytogenes, and mycobacterium tuberculosis. urgent treatment is required (anti-infective therapy and nonspecific supportive care). the aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review.201728336304
plants in our combating strategies against mycobacterium tuberculosis: progress made and obstacles met.traditionally used plants for treating chest-related problems/tuberculosis (tb) have not been evaluated in detail and hence a thorough study is needed in this regard. this knowledge may find application in developing new anti-tb drugs.201728385088
tuberculosis among foreign-born persons diagnosed ≥10 years after arrival in the united states, 2010-2015.the majority of tuberculosis (tb) cases in the united states are attributable to reactivation of latent tb infection (ltbi) (1). ltbi refers to the condition when a person is infected with mycobacterium tuberculosis without signs and symptoms, or radiographic or bacteriologic evidence of tb disease. cdc and the u.s. preventive services task force (uspstf) recommend screening populations at increased risk for ltbi, including persons who have lived in congregate settings at high risk and persons w ...201728333913
evaluation of pulmonary tuberculosis case detection improvement with the deployment of xpertmtb/rif in the tuberculosis control program of cross river state, nigeria.global indices show that nigeria has the highest tuberculosis (tb)-related mortality rate. overdependence on ziehl-neelsen (zn) smear microscopy for diagnosis and human immunodeficiency virus (hiv)/aids has limited control efforts. the new polymerase chain reaction-based xpertmtb/rif (cepheid inc., ca, usa), which detects mycobacterium tuberculosis and rifampicin resistance, was introduced in cross river state in 2014. we evaluated the increment in pulmonary tb case detection following introduct ...201728317812
tb-iris: proteomic analysis of in vitro pbmc responses to mycobacterium tuberculosis and response modulation by dexamethasone.paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (tb-iris) occurs in 8-54% of south african patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. improved tb-iris molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. we assessed how tb-iris status and dexamethasone influence leukocyte proteomic responses to mycobacterium tuberculosis (mtb). patient blood was obtained th ...201728209523
effector mechanisms of neutrophils within the innate immune system in response to mycobacterium tuberculosis infection.neutrophils have a significant yet controversial role in the innate immune response to mycobacterium tuberculosis (m. tb) infection, which is not yet fully understood. in addition to neutrophils' well-known effector mechanisms, they may also help control infection of m. tb through the formation of neutrophil extracellular traps (nets), which are thought to further promote the killing of m. tb by resident alveolar macrophages. cytokines such as ifn-γ have now been shown to serve an immunomodulato ...201728178208
ga(iii) nanoparticles inhibit growth of both mycobacterium tuberculosis and hiv and release of interleukin-6 (il-6) and il-8 in coinfected macrophages.treatment of individuals coinfected with human immunodeficiency virus (hiv) type 1 and mycobacterium tuberculosis is challenging due to the prolonged treatment requirements, drug toxicity, and emergence of drug resistance. mononuclear phagocytes (mp; macrophages) are one of the natural reservoirs for both hiv and m. tuberculosis here, the treatment of hiv and m. tuberculosis coinfection was studied by preloading human macrophages with mp-targeted gallium (ga) nanoparticles to limit subsequent si ...201728167548
tuberculosis 'the great imitator': a usual disease with unusual presentations.a number of infectious diseases have been referred to by the phrase 'the great imitator', of which the oldest is syphilis; others include lyme disease, nocardiosis, etc. tuberculosis has been described as the second great imitator as it can imitate various other disease processes. an awareness of the atypical clinical manifestations of tuberculosis is important, especially in regions where tuberculosis continues to be a major public health problem, such as india. extrapulmonary tuberculosis (ept ...201728166920
risk factors for readmission to hospital in patients with tuberculosis in tehran, iran: three-year surveillance.tuberculosis (tb) is still a major health problem and tb hospital readmission could increase health system costs. in a retrospective study in a tertiary referral hospital for tb in tehran, iran, tb patients with readmission were evaluated. these tb patients in the index year who were then readmitted were compared with tb patients in the same year who were not readmitted during the follow-up period. one hundred and forty-six patients had hospital readmission within three-year follow-up with mean ...201728166697
potential of zanthoxylum leprieurii as a source of active compounds against drug resistant mycobacterium tuberculosis.tuberculosis (tb) is still a global health problem mainly due to development of resistance and co-infection with the human immune virus (hiv). treatment of multi and extensively drug resistant tb requires use of second line drugs which are less efficacious, expensive and very toxic. this has necessitated a need to search for new treatment regimens especially from medicinal plants. zanthoxylum leprieurii, a plant species from rutaceae is used locally in the treatment of tuberculosis in uganda. th ...201728148252
hepatic tuberculosis in human immunodeficiency virus co-infected adults: a case series of south african adults.although mycobacterium tuberculosis (tb) infection may cause extrapulmonary disease in hiv-infected adults, hiv-associated hepatic tb has been poorly characterized. our objective was to describe hepatic tb in hiv-infected adults.201728148232
thoracic diseases associated with hiv infection in the era of antiretroviral therapy: clinical and imaging findings.the human immunodeficiency virus (hiv) and acquired immunodeficiency syndrome (aids) pandemic has entered its 4th decade. since the introduction of combination antiretroviral therapy (art) in 1996, the number of aids-related deaths has plateaued worldwide. today, owing to the effectiveness of art, the hiv-infected population is aging and hiv infection has become a chronic illness. non-aids comorbidities are increasing, and the spectrum of hiv-related thoracic diseases is evolving. in developed c ...201725019430
the role of uv radiation and vitamin d in the seasonality and outcomes of infectious disease.the seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. one of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (uvr), and its subsequent control of vitamin d production. here we show how uvr and vitamin d, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne ...201728078341
balancing trained immunity with persistent immune activation and the risk of simian immunodeficiency virus infection in infant macaques vaccinated with attenuated mycobacterium tuberculosis or mycobacterium bovis bcg vaccine.our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (hiv-1) and tuberculosis (tb) infections. the vaccine consists of an auxotroph mycobacterium tuberculosis strain that coexpresses hiv antigens. utilizing an infant rhesus macaque model, we have previously shown that this attenuated m. tuberculosis (amtb)-simian immunodeficiency virus (siv) vaccine is immunogenic, and although the vaccine did not prevent o ...201727655885
mycobacterial peritonitis in capd patients in limpopo: a 6-year cumulative report from a single center in south africa.south africa has one of the highest incidences of tuberculosis (tb) worldwide due to the ongoing human immunodeficiency virus (hiv) epidemic. there are, however, no reports on peritonitis in continuous ambulatory peritoneal dialysis (capd) patients due to mycobacterium tuberculosis in south africa. the aim of this study is to discuss our experience of tuberculous peritonitis in capd patients from a rural endemic area of south africa. this is a retrospective descriptive study of capd patients dia ...201727006437
trained immunity and susceptibility to hiv.in this issue of clinical and vaccine immunology, k. jensen et al. (clin vaccine immunol 24:e00360-16, 2017, https://doi.org/10.1128/cvi.00360-16) describe a dual-purpose attenuated mycobacterium tuberculosis-simian immunodeficiency virus vaccine (amtb-siv). interestingly, immunized infant macaques required fewer oral exposures to siv to become infected relative to nonimmunized animals. the authors hypothesized that augmented susceptibility to siv was due to activation of cd4(+) t cells through ...201727847369
transmission of extensively drug-resistant tuberculosis in south africa.background drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (hiv) infection worldwide. a widespread epidemic of extensively drug-resistant (xdr) tuberculosis is occurring in south africa, where cases have increased substantially since 2002. the factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. methods we conducted a prospective study involving 4 ...201728099825
hiv status among patients with tuberculosis and hiv testing practices by connecticut health care providers.knowing the human immunodeficiency virus (hiv) status of persons infected with mycobacterium tuberculosis is important for individual treatment and preventing transmission. this evaluation analyzed surveillance data and surveyed health care providers who care for patients with hiv and tuberculosis (tb) to understand the factors contributing to suboptimal levels of connecticut patients with tb having a known hiv status. during 2008 to 2010, 208 (76.2%) of 273 patients had a known hiv status; 12 ( ...201723442493
species dependent impact of helminth-derived antigens on human macrophages infected with mycobacterium tuberculosis: direct effect on the innate anti-mycobacterial response.in countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. while mycobacterium tuberculosis (mtb) gives rise to a pro-inflammatory th1 response, a th2 response is typical of helminth infections. a strong th2 response has been associated with decreased protection against tuberculosis.201728192437
integration of biomass formulations of genome-scale metabolic models with experimental data reveals universally essential cofactors in prokaryotes.the composition of a cell in terms of macromolecular building blocks and other organic molecules underlies the metabolic needs and capabilities of a species. although some core biomass components such as nucleic acids and proteins are evident for most species, the essentiality of the pool of other organic molecules, especially cofactors and prosthetic groups, is yet unclear. here we integrate biomass compositions from 71 manually curated genome-scale models, 33 large-scale gene essentiality data ...201727939572
engineering bacteria to manufacture functionalized polyester beads.the ability to generate tailor-made, functionalized polyester (polyhydroxyalkanoate, pha) beads in bacteria by harnessing their natural carbon-storage granule production system is an exciting recent development. proteins that naturally attach to the polyester granule core were rationally engineered to enable in vivo production of pha beads which are applicable in bioseparation, protein purification, enzyme immobilization and diagnostics and which show advantageous properties toward the developme ...201722705844
an interactive macrophage signal transduction map facilitates comparative analyses of high-throughput data.macrophages (mϕs) are key players in the coordination of the lifesaving or detrimental immune response against infections. the mechanistic understanding of the functional modulation of mϕs by pathogens and pharmaceutical interventions at the signal transduction level is still far from complete. the complexity of pathways and their cross-talk benefits from holistic computational approaches. in the present study, we reconstructed a comprehensive, validated, and annotated map of signal transduction ...201728137890
immunogenic properties of lactobacillus plantarum producing surface-displayed mycobacterium tuberculosis antigens.tuberculosis (tb) remains among the most deadly diseases in the world. the only available vaccine against tuberculosis is the bacille calmette-guérin (bcg) vaccine, which does not ensure full protection in adults. there is a global urgency for the development of an effective vaccine for preventing disease transmission, and it requires novel approaches. we are exploring the use of lactic acid bacteria (lab) as a vector for antigen delivery to mucosal sites. here, we demonstrate the successful exp ...201727815271
crystal structure and biochemical investigations reveal novel mode of substrate selectivity and illuminate substrate inhibition and allostericity in a subfamily of xaa-pro dipeptidases.xaa-pro dipeptidase (xpd) catalyzes hydrolysis of iminopeptide bond in dipeptides containing trans-proline as a second residue. xpds are found in all living organisms and are believed to play an essential role in proline metabolism. here, we report crystal structures and extensive enzymatic studies of xpd from xanthomonas campestris (xpdxc), the first such comprehensive study of a bacterial xpd. we also report enzymatic activities of its ortholog from mycobacterium tuberculosis (xpdmt). these en ...201727816563
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