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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
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
hybrid potential simulation of the acylation of enterococcus faecium l,d-transpeptidase by carbapenems.the l,d-transpeptidases, ldts, catalyze peptidoglycan cross-linking in β-lactam-resistant mutant strains of several bacteria, including enterococcus faecium and mycobacterium tuberculosis. although unrelated to the essential d,d-transpeptidases, which are inactivated by the β-lactam antibiotics, they are nevertheless inhibited by the carbapenem antibiotics, making them potentially useful targets in the treatment of some important diseases. in this work, we have investigated the acylation mechani ...201627196382
β-lactam resistance mechanisms: gram-positive bacteria and mycobacterium tuberculosis.the value of the β-lactam antibiotics for the control of bacterial infection has eroded with time. three gram-positive human pathogens that were once routinely susceptible to β-lactam chemotherapy-streptococcus pneumoniae, enterococcus faecium, and staphylococcus aureus-now are not. although a fourth bacterium, the acid-fast (but not gram-positive-staining) mycobacterium tuberculosis, has intrinsic resistance to earlier β-lactams, the emergence of strains of this bacterium resistant to virtually ...201627091943
ht-spoti: a rapid drug susceptibility test (dst) to evaluate antibiotic resistance profiles and novel chemicals for anti-infective drug discovery.antibiotic resistance is one of the major threats to global health and well-being. the past decade has seen an alarming rise in the evolution and spread of drug-resistant strains of pathogenic microbes. the emergence of extensively drug resistant (xdr) strains of mycobacterium tuberculosis and antimicrobial resistance among the eskape (enterococcus faecium, staphylococcus aureus, klebsiella pneumoniae, acinetobacter baumanii, pseudomonas aeruginosa, and enterobacter species) as well as fungal pa ...201626855282
investigation of c-5 alkynyl (alkynyloxy or hydroxymethyl) and/or n-3 propynyl substituted pyrimidine nucleoside analogs as a new class of antimicrobial agents.the resurgence of mycobacterial infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. a group of 5-ethynyl (6-10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5-(2-propynyloxy)-3-n-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-n-(2-propynyl) (30-33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [mycobacterium tuberculosis (mtb), mycobacterium bovis (bcg) and mycobac ...201627665179
an evolved oxazolidinone with selective potency against mycobacterium tuberculosis and gram positive bacteria.innovation of new antibacterials that are effective against strains that have developed resistance to existing drugs would strengthen our ability to treat and subsequently control spread of pathogenic bacteria. increasing incidence of infections with drug resistant bacteria has become a common occurrence in recent times. we have developed an evolved oxazolidinone, t145, which inhibits growth of enterococcus faecalis, staphylococcus aureus and mycobacterium tuberculosis (mtb) with sub μg/ml poten ...201627329794
in silico dissection of type vii secretion system components across bacteria: new directions towards functional characterization.type vii secretion system (t7ss) is one of the factors involved in virulence of mycobacterium tuberculosis h37rv. numerous research efforts have been made in the last decade towards characterizing the components of this secretion system. an extensive genome-wide analysis through compilation of isolated information is required to obtain a global view of diverse characteristics and pathogenicity-related aspects of this machinery. the present study suggests that differences in structural components ...201626949095
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
a novel inhibition elisa for the detection and monitoring of penicillium marneffei antigen in human serum.the thermally dimorphic fungus penicillium marneffei is a causative agent of penicilliosis marneffei, a disease considered to be an acquired immune deficiency syndrome (aids)-defining illness in southeast asia and southern china. we have developed an inhibition enzyme-linked immunosorbent assay (inh-elisa) incorporating the yeast phase specific mannoprotein-binding monoclonal antibody 4d1 for the detection of p. marneffei infection. in our sample set, the test detected antigenemia in all 45 (100 ...201626838686
cyp51a-based mechanism of azole resistance in aspergillus fumigatus: illustration by a new 3d structural model of aspergillus fumigatus cyp51a protein.mutations of cyp51a protein (cytochrome p450 14-α sterol demethylase) play a central role in the azole resistance of aspergillus fumigatus the available structural models of cyp51a protein ofa. fumigatus are built based on that of homo sapiens and that of mycobacterium tuberculosis, of which the amino acid homology is only 38% and 29% compared with cyp51a protein ofa. fumigatus, respectively. in the present study, we constructed a new 3d structural model ofa. fumigatus cyp51a protein based on a ...201626768370
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
long term outcome of medical and surgical co-management of craniospinal aspergillosis in an immunocompromised patient.35 yr old steroid dependent lady with pulmonary tb underwent debridement of epidural abscess & posterior stabilization for paraparesis. with histopathology and cultures showing aspergillus fumigatus, voricanozole was started. by the fourth week, she developed persistent fever, and altered mental status. brain mri and csf study including multiplex pcr evaluation confirmed cerebral aspergillosis. voricanozole was changed to intravenous lipid complex amphotericin b to achieve sustained clinical and ...201628053849
evaluation of exposure of pemphigus vulgaris patients to mycobacterium tuberculosis and aspergillus fumigatus.the purpose of this study was to screen pemphigus vulgaris (pv) (autoimmune bullous skin disease) for the presence of immunoglobulin g against mycobacterium tuberculosis and aspergillus fumigatus. the sera of 60 pv patients and 28 controls were screened for the presence of immunoglobulin g against m. tuberculosis and a. fumigatus by enzyme-linked immune-sorbent assay. forty patients were females and 20 were males. the range of igg against m. tuberculosis was from 0.9 to 152.6 (median = 2.95) in ...201627396270
cerebral aspergillosis and pulmonary tuberculosis in a child with chronic granulomatous disease.chronic granulomatous disease (cgd) is an immune disorder that affects phagocytes. it is characterized by recurrent or persistent bacterial and fungal infections. reports of tuberculosis (tb) in patients with cgd are rare. in developing countries, where tb is endemic, possibility of other chronic infections is often overlooked by physicians.201627308089
invasive forms of candida and aspergillus in sputum samples of pulmonary tuberculosis patients attending the tuberculosis reference laboratory in ghaemshahr, northern iran: an analysis of samples collected during the past 10years.tuberculosis (tb) continues to be a major public health problem worldwide. this is especially true in northern iran, which has high tb prevalence. the chronic nature of this disease is further exacerbated if it is accompanied by fungal infection, which usually remains undiagnosed and thus untreated. thus, mycotic infections add fatal dimensions to pulmonary tb. our objective was to determine the prevalence of invasive forms of fungal elements in sputum samples collected from patients with pulmon ...201628043539
fibrosing mediastinitis due to aspergillus with dominant cardiac involvement: report of two autopsy cases with review of literature.fibrosing mediastinitis (fm) is a rare condition characterized by extensive proliferation of fibrous tissue in the mediastinum resulting in mass like lesion. histoplasma and mycobacterium tuberculosis are the common infective causes of fibrosing mediastinitis, but aspergillus infection is an extremely rare cause. fibrosing mediastinitis due to aspergillus usually occurs following aspergillus bronchopneumonia. cardiac involvement due to aspergillus-related fibrosing mediastinitis is extremely rar ...201624998315
evidence of co-infection with mycobacterium bovis and tick-borne pathogens in a naturally infected sheep flock.ticks are responsible for the transmission of pathogens of veterinary importance, including those affecting sheep. the current study was designed to investigate co-infections with tick-borne and other pathogens in a naturally infected sheep flock with poor health condition using serology and pcr. infection with anaplasma ovis was detected by serology and pcr in 56% of the animals. the presence of rickettsia spp. of the spotted fever group (sfg) was detected by pcr and sequence analysis in 31% of ...201626726806
the effect of deworming on tests of tuberculosis infection in children with recent tuberculosis exposure: a randomized controlled trial.helminth infestations are associated with t-helper cell type 2 (th2) immune responses, leading to suppression of th1 responses required to control mycobacterium tuberculosis infection. we hypothesized that deworming after documented m. tuberculosis exposure might improve th1 immune responses.201626933841
penicillium chrysogenum dsoa associated with marine sponge (tedania anhelans) exhibit antimycobacterial activity.a strain of penicillium chrysogenum was isolated from tedania anhelans (marine sponge) collected from indian ocean (8°22'30″n latitude and 76°59'16″ longitude) and deposited in culture collection centers. the strain subjected to different culture conditions for production of extrolites were extracted using ethyl acetate and chloroform. when both extracts were subjected for antibacterial activity, latter had high activity. minimum inhibitory concentration of chloroform extract ranged from 31.25-1 ...201626717859
fragment-based whole cell screen delivers hits against m. tuberculosis and non-tuberculous mycobacteria.reactive multi-target 'fragment drugs' represent critical components of current tuberculosis regimens. these compounds, such as pyrazinamide, are old synthetic antimycobacterials that are activated inside mycobacterium tuberculosis bacilli and are smaller than the usual drug-like, single-target molecules. based on the success of small 'dirty' drugs in the chemotherapy of tuberculosis, we suggested previously that fragment-based whole cell screens should be introduced in our current antimycobacte ...201627656168
toxin-antitoxin systems in clinical pathogens.toxin-antitoxin (ta) systems are prevalent in bacteria and archaea. although not essential for normal cell growth, ta systems are implicated in multiple cellular functions associated with survival under stress conditions. clinical strains of bacteria are currently causing major human health problems as a result of their multidrug resistance, persistence and strong pathogenicity. here, we present a review of the ta systems described to date and their biological role in human pathogens belonging t ...201627447671
antimicrobial resistance prediction in patric and rast.the emergence and spread of antimicrobial resistance (amr) mechanisms in bacterial pathogens, coupled with the dwindling number of effective antibiotics, has created a global health crisis. being able to identify the genetic mechanisms of amr and predict the resistance phenotypes of bacterial pathogens prior to culturing could inform clinical decision-making and improve reaction time. at patric (http://patricbrc.org/), we have been collecting bacterial genomes with amr metadata for several years ...201627297683
infectious cause of death determination using minimally invasive autopsies in developing countries.in developing countries, the knowledge of the microorganisms causing fatal infections is critical and could help designing and implementing more effective preventive interventions and treatment guidelines. we aimed to develop and validate protocols for microbiological analysis in post-mortem samples obtained during minimally invasive autopsy (mia) procedures and to assess their performance. thirty mias performed in adults at maputo central hospital in southern mozambique were included in the ana ...201626508103
n-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions.mycobacterium tuberculosis infection is thought to induce oxidative stress. n-acetyl-cysteine (nac) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. here, we tested whether nac exerts a direct antibiotic activity against mycobacteria.201627793104
a patient presenting with tuberculous encephalopathy and human immunodeficiency virus infection.in the usa, mycobacterium tuberculosis infection is more likely to be found in foreign-born individuals, and those co-infected with human immunodeficiency virus (hiv) are more likely to have tuberculous meningitis. the literature is lacking in details about the clinical workup of patients presenting with tuberculous meningitis with encephalopathic features who are co-infected with hiv. this report demonstrates a clinical approach to diagnosis and management of tuberculous meningitis.201627302013
potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis.treatment of multidrug-resistant tuberculosis (mdr-tb) is extremely challenging due to the virulence of the etiologic strains of mycobacterium tuberculosis (m. tb), the aberrant host immune responses and the diminishing treatment options with tb drugs. new treatment regimens incorporating therapeutics targeting both m. tb and host factors are urgently needed to improve the clinical management outcomes of mdr-tb. host-directed therapies (hdt) could avert destructive tuberculous lung pathology, fa ...201627301245
toll-like receptor 2 mediates in vivo pro- and anti-inflammatory effects of mycobacterium tuberculosis and modulates autoimmune encephalomyelitis.mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. we show here that both effects are mediated by toll-like receptor 2 (tlr2), by exploiting a previously characterized tlr2 variant (met82ile). tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific foxp3(+) tregs, while tlr2 82met impairs the expansion of tregs and reduces the production of ifn-γ and il-17 proinflammatory cytokines. preferential dimerization wit ...201627252700
molecular identification of mycobacterium bovis from cattle and human host in mali: expanded genetic diversity.bovine tuberculosis (btb) is a contagious, debilitating human and animal disease caused by mycobacterium bovis, a member of the mycobacterium tuberculosis complex. the study objective were to estimate the frequency of btb, examine genetic diversity of the m. bovis population in cattle from five regions in mali and to determine whether m. bovis is involved in active tuberculosis (tb) in humans. samples from suspected lesions on cattle at the slaughterhouses were collected. mycobacterial smear, cu ...201627439708
emerging tuberculosis pathogen hijacks social communication behavior in the group-living banded mongoose (mungos mungo).an emerging mycobacterium tuberculosis complex (mtc) pathogen, m. mungi, infects wild banded mongooses (mungos mungo) in northern botswana, causing significant mortality. this mtc pathogen did not appear to be transmitted through a primary aerosol or oral route. we utilized histopathology, spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats (miru-vntr), quantitative pcr (qpcr), and molecular markers (regions of difference [rds] from various mtc members, i ...201627165798
comparative proteomics identifies host immune system proteins affected by infection with mycobacterium bovis.mycobacteria of the mycobacterium tuberculosis complex (mtbc) greatly impact human and animal health worldwide. the mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. eurasian wild boar (sus scrofa) are natural reservoir hosts for mtbc and a model for mycobacterial infection and tuberculosis (tb). in the wild boar tb model, mycobacterial infection affects the expression of innate and adaptive immune respons ...201627027307
vapcs of mycobacterium tuberculosis cleave rnas essential for translation.the major human pathogen mycobacterium tuberculosis can survive in the host organism for decades without causing symptoms. a large cohort of toxin-antitoxin (ta) modules contribute to this persistence. of these, 48 ta modules belong to the vapbc (virulence associated protein) gene family. vapc toxins are pin domain endonucleases that, in enterobacteria, inhibit translation by site-specific cleavage of initiator trna. in contrast, vapc20 of m. tuberculosis inhibits translation by site-specific cl ...201627599842
a study of parasitic and bacterial pathogens associated with diarrhea in hiv-positive patients.diarrhea is a common complication of acquired immune deficiency syndrome (aids), occurring in almost 90% of aids patients in developing countries like india. the present study was aimed to determine the prevalence and microbiological profile of pathogens associated with diarrhea in human immunodeficiency virus (hiv) positive patients and their relation to cd4 counts.201627795876
establishing virulence associated polyphosphate kinase 2 as a drug target for mycobacterium tuberculosis.inorganic polyphosphate (polyp) plays an essential role in microbial stress adaptation, virulence and drug tolerance. the genome of mycobacterium tuberculosis encodes for two polyphosphate kinases (ppk-1, rv2984 and ppk-2, rv3232c) and polyphosphatases (ppx-1, rv0496 and ppx-2, rv1026) for maintenance of intracellular polyp levels. microbial polyphosphate kinases constitute a molecular mechanism, whereby microorganisms utilize polyp as phosphate donor for synthesis of atp. in the present study w ...201627279366
acute tuberculous myopericarditis mimicking acute myocardial infarction: a case report and literature review.a number of cases of acute myopericarditis mimicking acute myocardial infarction (ami) have previously been reported in the literature. however, to the best of our knowledge, such a case resulting from mycobacterium tuberculosis infection has not previously been described. the present study reports the case of a 21-year-old male patient presenting with acute chest pain, in whom focal st-segment elevation and elevated cardiac enzymes mimicked a diagnosis of ami. however, acute tuberculous myoperi ...201627284323
spotyping: fast and accurate in silico mycobacterium spoligotyping from sequence reads.spotyping is a fast and accurate program for in silico spoligotyping of mycobacterium tuberculosis isolates from next-generation sequencing reads. this novel method achieves high accuracy for reads of both uniform and varying lengths, and is about 20 to 40 times faster than spolpred. spotyping also integrates the function of producing a report summarizing associated epidemiological data from a global database of all isolates having the same spoligotype. spotyping is freely available at: https:// ...201626883915
how old are bacterial pathogens?only few molecular studies have addressed the age of bacterial pathogens that infected humans before the beginnings of medical bacteriology, but these have provided dramatic insights. the global genetic diversity of helicobacter pylori, which infects human stomachs, parallels that of its human host. the time to the most recent common ancestor (tmrca) of these bacteria approximates that of anatomically modern humans, i.e. at least 100 000 years, after calibrating the evolutionary divergence withi ...201627534956
chaperone addiction of toxin-antitoxin systems.bacterial toxin-antitoxin (ta) systems, in which a labile antitoxin binds and inhibits the toxin, can promote adaptation and persistence by modulating bacterial growth in response to stress. some atypical ta systems, known as tripartite toxin-antitoxin-chaperone (tac) modules, include a molecular chaperone that facilitates folding and protects the antitoxin from degradation. here we use a tac module from mycobacterium tuberculosis as a model to investigate the molecular mechanisms by which class ...201627827369
tuberculous meningitis is a major cause of mortality and morbidity in adults with central nervous system infections in kota kinabalu, sabah, malaysia: an observational study.central nervous system (cns) infections are a significant contributor to morbidity and mortality globally. however, most published studies have been conducted in developed countries where the epidemiology and aetiology differ significantly from less developed areas. additionally, there may be regional differences due to variation in the socio-economic levels, public health services and vaccination policies. currently, no prospective studies have been conducted in sabah, east malaysia to define t ...201627306100
differential diagnosis and treatment of acute cauda equina syndrome in the human immunodeficiency virus positive patient: a case report and review of the literature.acute cauda equina syndrome is an uncommon but significant neurologic presentation due to a variety of underlying diseases. anatomical compression of nerve roots, usually by a lumbar disk hernia is a common cause in the general population, while inflammatory, neoplastic, and ischemic causes have also been recognized. among human immunodeficiency virus (hiv) infected patients with acquired immunodeficiency syndrome, infectious causes are encountered more frequently, the most prevalent of which ar ...201627268102
vanishing retinal arterial aneurysms with anti-tubercular treatment in a patient presenting with idiopathic retinal vasculitis, aneurysms, and neuroretinitis.idiopathic retinal vasculitis, aneurysms, and neuroretinitis (irvan) syndrome presents with characteristic clinical manifestations such as aneurysms at arteriolar bifurcations and optic nerve and retinal vascular inflammation. regression of such features on treatment with anti-tubercular therapy (att) combined with corticosteroids has not been reported in literature.201626922651
neuro-sweet disease with positive modified acid-fast staining of the cerebrospinal fluid: a case report.neuro-sweet disease (nsd) is sweet disease with central nervous system (cns) involvement. to the best of our knowledge, the present case report is the first to describe nsd complicated by endogenous infection with mycobacterium tuberculosis. the present case report describes a male patient who developed nsd-induced meningitis, which initially manifested as a fever, headache and neck stiffness. painful erythematous plaques subsequently developed on his face, neck and upper trunk. brain magnetic r ...201627073429
tuberculosis-associated hemophagocytic lymphohistiocytosis in adolescent diagnosed by polymerase chain reaction.we present a case of tuberculosis-associated hemophagocytic lymphohistiocytosis in a 14-year-old girl. the patient presented with weight loss, malaise, fatigue, prolonged fever, and generalized lymphadenopathy. laboratory investigation revealed pancytopenia (white blood cells, 2,020 cells/µl; hemoglobin, 10.2 g/dl; platelets, 52,000 cells/µl), hypertriglyceridemia (229 mg/dl), and hyperferritinemia (1,420 ng/ml). bone marrow biopsy showed a hypocellular bone marrow with a large numbers of histio ...201626893604
rv2744c is a pspa ortholog that regulates lipid droplet homeostasis and nonreplicating persistence in mycobacterium tuberculosis.mycobacterium tuberculosis, the causative agent of tuberculosis (tb), remains a significant cause of morbidity and mortality worldwide, despite the availability of a live attenuated vaccine and anti-tb antibiotics. the vast majority of individuals infected with m. tuberculosis develop an asymptomatic latent infection in which the bacterium survives within host-generated granulomatous lesions in a physiologically altered metabolic state of nonreplicating persistence. the granuloma represents an a ...201627002134
in vitro antimicrobial activities of animal-used quinoxaline 1,4-di-n-oxides against mycobacteria, mycoplasma and fungi.the quinoxaline 1,4-di-n-oxides (qdnos) were known as potent antibacterial agents. for the purpose of evaluating the bioactivity of existing animal-used qdnos drugs against representative pathogenic microorganism, the representative drugs of quinoxalines including cyadox, mequindox, quinocetone and their metabolites were submitted to the in vitro evaluation for antituberculosis, antimycoplasma, antifungal and antiviral activities.201627600955
dual-reporter mycobacteriophages (φ2drms) reveal preexisting mycobacterium tuberculosis persistent cells in human sputum.persisters are the minor subpopulation of bacterial cells that lack alleles conferring resistance to a specific bactericidal antibiotic but can survive otherwise lethal concentrations of that antibiotic. in infections with mycobacterium tuberculosis, such persisters underlie the need for long-term antibiotic therapy and contribute to treatment failure in tuberculosis cases. here, we demonstrate the value of dual-reporter mycobacteriophages (φ(2)drms) for characterizing m. tuberculosis persisters ...201627795387
il-1β, but not programed death-1 and programed death ligand pathway, is critical for the human th17 response to mycobacterium tuberculosis.the programed death-1 (pd-1)-programed death ligand-1 (pd-l1) and pd-l2 co-inhibitory pathway has been implicated in the evasion strategies of mycobacterium tuberculosis. specifically, m. tuberculosis-induced pd-l1 orchestrates expansion of regulatory t cells and suppression of th1 response. however, the role of pd pathway in regulating th17 response to m. tuberculosis has not been investigated. in the present report, we demonstrate that m. tuberculosis and m. tuberculosis-derived antigen fracti ...201627867382
the listeria monocytogenes pasta kinase prka and its substrate yvck are required for cell wall homeostasis, metabolism, and virulence.obstacles to bacterial survival and replication in the cytosol of host cells, and the mechanisms used by bacterial pathogens to adapt to this niche are not well understood. listeria monocytogenes is a well-studied gram-positive foodborne pathogen that has evolved to invade and replicate within the host cell cytosol; yet the mechanisms by which it senses and responds to stress to survive in the cytosol are largely unknown. to assess the role of the l. monocytogenes penicillin-binding-protein and ...201627806131
the mannose receptor is involved in the phagocytosis of mycobacteria-induced apoptotic cells.upon mycobacterium tuberculosis infection, macrophages may undergo apoptosis, which has been considered an innate immune response. the pathways underlying the removal of dead cells in homeostatic apoptosis have been extensively studied, but little is known regarding how cells that undergo apoptotic death during mycobacterial infection are removed. this study shows that macrophages induced to undergo apoptosis with mycobacteria cell wall proteins are engulfed by j-774a.1 monocytic cells through t ...201627413759
autophagy induction targeting mtorc1 enhances mycobacterium tuberculosis replication in hiv co-infected human macrophages.to survive and replicate in macrophages mycobacterium tuberculosis (mtb) has developed strategies to subvert host defence mechanisms, including autophagy. autophagy induction has the potential to clear mtb, but little is known about its effect during controlled tuberculosis and hiv co-infection. mammalian target of rapamycin complex1 (mtorc1) inhibitors were used to induce autophagy in human macrophages pre-infected with hiv-1bal and infected with a low dose of mtb (co-infected), or single mtb i ...201627302320
fine-tuning of macrophage activation using synthetic rocaglate derivatives.drug-resistant bacteria represent a significant global threat. given the dearth of new antibiotics, host-directed therapies (hdts) are especially desirable. as ifn-gamma (ifnγ) plays a central role in host resistance to intracellular bacteria, including mycobacterium tuberculosis, we searched for small molecules to augment the ifnγ response in macrophages. using an interferon-inducible nuclear protein ipr1 as a biomarker of macrophage activation, we performed a high-throughput screen and identif ...201627086720
endosomal mr1 trafficking plays a key role in presentation of mycobacterium tuberculosis ligands to mait cells.mucosal-associated invariant t (mait) cells, present in high frequency in airway and other mucosal tissues, have th1 effector capacity positioning them to play a critical role in the early immune response to intracellular pathogens, including mycobacterium tuberculosis (mtb). mr1 is a highly conserved class i-like molecule that presents vitamin b metabolites to mait cells. the mechanisms for loading these ubiquitous small molecules are likely to be tightly regulated to prevent inappropriate mait ...201627031111
pe_pgrs33 contributes to mycobacterium tuberculosis entry in macrophages through interaction with tlr2.pe_pgrs represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an n-terminal pe domain followed by a large gly-ala repeat-rich c-terminal domain. despite the abundance of pe_pgrs-coding genes in the mycobacterium tuberculosis (mtb) genome their role and function in the biology and pathogenesis still remains elusive. in this study, we generated and characterized an mtb h37rv mutant (mtbδ33) in which the structural gene of pe_pgrs33, a prototypic ...201626978522
implementation of a collaborative series of classroom-based undergraduate research experiences spanning chemical biology, biochemistry, and neurobiology.classroom undergraduate research experiences (cures) provide students access to the measurable benefits of undergraduate research experiences (ures). herein, we describe the implementation and assessment of a novel model for cohesive cures focused on central research themes involving faculty research collaboration across departments. specifically, we implemented three collaborative cures spanning chemical biology, biochemistry, and neurobiology that incorporated faculty members' research interes ...201627810870
the toxin-antitoxin system dartg catalyzes reversible adp-ribosylation of dna.the discovery and study of toxin-antitoxin (ta) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell death. here we identify and characterize a ta system found in various bacteria, including the global pathogen mycobacterium tuberculosis. the toxin of the system (dart) is a domain of unknown function ...201627939941
imaging the nadh:nad(+) homeostasis for understanding the metabolic response of mycobacterium to physiologically relevant stresses.the nadh:nad(+) ratio is the primary indicator of the metabolic state of bacteria. nad(h) homeostasis is critical for mycobacterium tuberculosis (mtb) survival and is thus considered an important drug target, but the spatio-temporal measurements of nad(h) remain a challenge. genetically encoded fluorescent biosensors of the nadh:nad(+) ratios were recently described, paving the way for investigations of the metabolic state of pathogens during infection. here we have adapted the genetically encod ...201627878107
mycobacterium tuberculosis transcription machinery: ready to respond to host attacks.regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. for pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. inappropriate responses have consequences; h ...201626883824
crystal structures of mycobacterium tuberculosis hspat and arat reveal structural basis of their distinct substrate specificities.aminotransferases of subfamily iβ, which include histidinol phosphate aminotransferases (hspats) and aromatic amino acid aminotransferases (arats), are structurally similar but possess distinct substrate specificities. this study, encompassing structural and biochemical characterisation of hspat and arat from mycobacterium tuberculosis demonstrates that the residues lining the substrate binding pocket and n-terminal lid are the primary determinants of their substrate specificities. in mhspat, hy ...201626738801
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