Publications

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detection of enterotoxigenic e. coli in hospitalised children with and without diarrhoea in blantyre, malawi.drug susceptibility testing (dst) of mycobacterium tuberculosis (mtb) isolates is crucial for the effective treatment of tuberculosis. data on dst patterns in mtb isolates in childhood tuberculosis are scanty.201627077609
subunit protein vaccine delivery system for tuberculosis based on hepatitis b virus core vlp (hbc-vlp) particles.despite the development of modern medicine, tuberculosis (tb), caused by the pathogenic bacterium, mycobacterium tuberculosis (mtb), remains one of the deadliest diseases. this bacterium can lay dormant in individuals and get activated when immunity goes down and has also shown considerable prowess in mutating into drug resistant forms. the global emergence of such drug resistant mtb and the lack of efficacy of bacille calmette guérin (bcg), the only vaccine available so far, have resulted in a ...201627076312
consequences of cas9 cleavage in the chromosome of escherichia coli.the rna-guided cas9 nuclease from crispr-cas systems has emerged as a powerful biotechnological tool. the specificity of cas9 can be reprogrammed to cleave desired sequences in a cell's chromosome simply by changing the sequence of a small guide rna. unlike in most eukaryotes, cas9 cleavage in the chromosome of bacteria has been reported to kill the cell. however, the mechanism of cell death remains to be investigated. bacteria mainly rely on homologous recombination (hr) with sister chromosomes ...201627060147
identifying lineage effects when controlling for population structure improves power in bacterial association studies.bacteria pose unique challenges for genome-wide association studies because of strong structuring into distinct strains and substantial linkage disequilibrium across the genome(1,2). although methods developed for human studies can correct for strain structure(3,4), this risks considerable loss-of-power because genetic differences between strains often contribute substantial phenotypic variability(5). here, we propose a new method that captures lineage-level associations even when locus-specific ...201627572646
design, synthesis, structural elucidation, pharmacological evaluation of metal complexes with pyrazoline derivatives.a bioactive pyrazoline derivatives have been synthesized by the base-catalyzed claisen-schmidt condensation of imidazole-2-carboxaldehyde with 1-acetyl-2-hydroxynaphthalene followed by cyclization with phenylhydrazine (l(1))/2,3-dimethylphenylhydrazine (l(2)) and 3-nitrophenylhydrazine (l(3)). the metal(ii) complexes [ni(ii), co(ii), cu(ii) and zn(ii)] were formed by reacting the corresponding metal acetates with the ligands. all complexes were characterized by elemental analyses, electronic, ir ...201627537519
fluorescence-based assay for polyprenyl phosphate-glcnac-1-phosphate transferase (weca) and identification of novel antimycobacterial weca inhibitors.polyprenyl phosphate-glcnac-1-phosphate transferase (weca) is an essential enzyme for the growth of mycobacterium tuberculosis (mtb) and some other bacteria. mtb weca catalyzes the transformation from udp-glcnac to decaprenyl-p-p-glcnac, the first membrane-anchored glycophospholipid that is responsible for the biosynthesis of mycolylarabinogalactan in mtb. inhibition of weca will block the entire biosynthesis of essential cell wall components of mtb in both replicating and non-replicating states ...201627530653
m. tuberculosis ferritin (rv3841): potential involvement in amikacin (ak) & kanamycin (km) resistance.tuberculosis is an infectious disease, caused by one of the most successful human pathogen, mycobacterium tuberculosis. aminoglycosides, amikacin (ak) & kanamycin (km) are commonly used to treat drug resistant tuberculosis. they target the protein synthesis machinery by interacting with several steps of translation. several explanations have been proposed to explain the mechanism of aminoglycoside resistance but still our information is inadequate. iron storing/interacting proteins were found to ...201627521892
mycobacterium tuberculosis h37ra: a surrogate for the expression of conserved, multimeric proteins of m.tb h37rv.obtaining sufficient quantities of recombinant m.tb proteins using traditional approaches is often unsuccessful. several enzymes of the glycolytic cycle are known to be multifunctional, however relatively few enzymes from m.tb h37rv have been characterized in the context of their enzymatic and pleiotropic roles. one of the primary reasons is the difficulty in obtaining sufficient amounts of functionally active protein.201627514669
systematic analysis of the lysine acetylome of the pathogenic bacterium spiroplasma eriocheiris reveals acetylated proteins related to metabolism and helical structure.post-translational modifications such as acetylation are an essential regulatory mechanism of protein function. spiroplasma eriocheiris, with no cell wall and a helical structure, is a novel pathogen of freshwater crustacean. there is no other evidence of acylation (such as succinylation and propionylation) except acetylation genes in s. eriocheiris concise genome. so the acetylation may play an important role in s. eriocheiris. here, we conducted the first lysine acetylome in s. eriocheiris. we ...201627498276
expression, purification and characterization of esx-1 secretion-associated protein espl from mycobacterium tuberculosis.the esx-1 cluster encodes a special secretion system that is important for granuloma formation and virulence when mycobacterium tuberculosis infects the host. as one of the 'core' genes in the cluster, rv3880c gene codes an esx-1 secretion-associated protein espl from mycobacterium tuberculosis (mtespl). it has been reported that espl had a strong influence on the secretion of other two virulence factors, esxa and espe. however, so far little is known about the tertiary structure and specific fu ...201627496726
a recombinant trivalent fusion protein f1-lcrv-hsp70(ii) augments humoral and cellular immune responses and imparts full protection against yersinia pestis.plague is one of the most dangerous infections in humans caused by yersinia pestis, a gram-negative bacterium. despite of an overwhelming research success, no ideal vaccine against plague is available yet. it is well established that f1/lcrv based vaccine requires a strong cellular immune response for complete protection against plague. in our earlier study, we demonstrated that hsp70(ii) of mycobacterium tuberculosis modulates the humoral and cellular immunity of f1/lcrv vaccine candidates indi ...201627458447
functional role of putative critical residues in mycobacterium tuberculosis rnase p protein.rnase p is involved in processing the 5' end of pre-trna molecules. bacterial rnase p contains a catalytic rna subunit and a protein subunit. in this study, we have analyzed the residues in rnase p protein of m. tuberculosis that differ from the residues generally conserved in other bacterial rnase ps. the residues investigated in the current study include the unique residues, val27, ala70, arg72, ala77, and asp124, and also phe23 and arg93 which have been found to be important in the function o ...201627417238
the chromosomal parde2 toxin-antitoxin system of mycobacterium tuberculosis h37rv: genetic and functional characterization.mycobacterium tuberculosis h37rv escapes host-generated stresses by entering a dormant persistent state. activation of toxin-antitoxin modules is one of the mechanisms known to trigger such a state with low metabolic activity. m. tuberculosis harbors a large number of ta systems mostly located within discernible genomic islands. we have investigated the parde2 operon of m. tuberculosis h37rv encoding mpare2 toxin and mpard2 antitoxin proteins. the parde2 locus was transcriptionally active from g ...201627379032
cooperative stabilization of mycobacterium tuberculosis rrnap3 promoter open complexes by rbpa and card.the essential mycobacterial transcriptional regulators rbpa and card act to modulate transcription by associating to the initiation complex and increasing the flux of transcript production. each of these factors interacts directly with the promoter dna template and with rna polymerase (rnap) holoenzyme. we recently reported on the energetics of card-mediated open complex stabilization on the mycobacterium tuberculosis rrnap3 ribosomal promoter using a stopped-flow fluorescence assay. here, we ap ...201627342278
the secb-like chaperone rv1957 from mycobacterium tuberculosis: crystallization and x-ray crystallographic analysis.protein export is important in all bacteria, and bacteria have evolved specialized export machineries to fulfil this task. in mycobacterium tuberculosis, the causative agent of tuberculosis, the general secretion pathway (sec pathway) is conserved and is essential in performing the export of proteins. the bacterial sec pathway post-translationally exports unfolded proteins out of the cytoplasm, and the core of the sec pathway is composed of a heterotrimeric membrane-embedded channel, secyeg, and ...201627303898
g protein-coupled receptor160 regulates mycobacteria entry into macrophages by activating erk.mycobacterium tuberculosis (mtb), the causative agent of tuberculosis, invades and replicates within susceptible hosts by disturbing host antimicrobial mechanisms. although g protein-coupled receptors (gpcrs) are involved in most physiological and pathological activities of mammalian cells, the roles of gpcrs in mtb invasion into host cell remain elusive. here, we report that gpr160 expression is elevated at both mrna and protein level in macrophages in response to bcg infection. both the piggyb ...201627259691
phosphorylation modulates catalytic activity of mycobacterial sirtuins.sirtuins are nad(+)-dependent deacetylases involved in the regulation of diverse cellular processes and are conserved throughout phylogeny. here we report about in vitro transphosphorylation of the only nad(+)-dependent deacetylase (mdac) present in the genome of mycobacterium tuberculosis by eukaryotic-type ser/thr kinases, particularly pkna. the phosphorylated mdac displayed decreased deacetylase activity compared to its unphosphorylated counterpart. mass-spectrometric study identified seven p ...201627242704
description of compensatory gyra mutations restoring fluoroquinolone susceptibility in mycobacterium tuberculosis.resistance to fluoroquinolones (fqs) in mycobacterium tuberculosis (mtb) is mainly due to mutations in dna gyrase (gyra2b2), with the most common substitutions located at positions 90 and 94 in gyra. two clinical mdr mtb (mdr-tb) strains harbouring an a90e or d94n substitution in gyra were found to be surprisingly susceptible to fqs (ofloxacin mic ≤2 mg/l). we studied the impact of the additional gyra substitutions found in these strains (t80a and t80a + a90g, respectively) on fq susceptibility.201627234461
high-voltage electron microscopy tomography and structome analysis of unique spiral bacteria from the deep sea.structome analysis is a useful tool for identification of unknown microorganisms that cannot be cultured. in 2012, we discovered a unique deep-sea microorganism with a cell structure intermediate between those of prokaryotes and eukaryotes and described its features using freeze-substitution electron microscopy and structome analysis (quantitative and three-dimensional structural analysis of a whole cell at the electron microscopic level). we named it myojin parakaryote here we describe, using s ...201627230559
reaction mechanism of mycobacterium tuberculosis glutamine synthetase using quantum mechanics/molecular mechanics calculations.this paper is devoted to the understanding of the reaction mechanism of mycobacterium tuberculosis glutamine synthetase (mtgs) with atomic detail, using computational quantum mechanics/molecular mechanics (qm/mm) methods at the oniom m06-d3/6-311++g(2d,2p):ff99sb//b3lyp/6-31g(d):ff99sb level of theory. the complete reaction undergoes a three-step mechanism: the spontaneous transfer of phosphate from atp to glutamate upon ammonium binding (ammonium quickly loses a proton to asp54), the attack of ...201627225077
chemogenomics and orthology-based design of antibiotic combination therapies.combination antibiotic therapies are being increasingly used in the clinic to enhance potency and counter drug resistance. however, the large search space of candidate drugs and dosage regimes makes the identification of effective combinations highly challenging. here, we present a computational approach called indigo, which uses chemogenomics data to predict antibiotic combinations that interact synergistically or antagonistically in inhibiting bacterial growth. indigo quantifies the influence ...201627222539
antigenic characterization of dimorphic surface protein in mycobacterium tuberculosis.the mycobacterium tuberculosis rv0679c protein is a surface protein that contributes to host cell invasion. we previously showed that a single nucleotide transition of the rv0679c gene leads to a single amino acid substitution from asparagine to lysine at codon 142 in the beijing genotype family. in this study, we examined the immunological effect of this substitution. several recombinant proteins were expressed in escherichia coli and mycobacterium smegmatis and characterized with antisera and ...201627190237
therapeutic effect of recombinant mutated interleukin 11 in the mouse model of tuberculosis.earlier we demonstrated that blocking of interleukin 11 (il-11) by systemic administration of anti-il-11 antibodies attenuates severity of mycobacterium tuberculosis infection in mice. the substitution w147a in the il-11 molecule creates the form of cytokine capable to disrupt gp130/il11r signaling complex formation, thus serving as a high-affinity specific antagonist of il-11-mediated signaling. we hypothesized that this mutant form of il-11 may serve as an effective tool for inhibition of nati ...201627190186
antibacterial activities of medicinal plants used in mexican traditional medicine.we provide an extensive summary of the in vitro antibacterial properties of medicinal plants popularly used in mexico to treat infections, and we discuss the ethnomedical information that has been published for these species.201627155134
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
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
importance of the α10 helix for devr activation: a road map for screening inhibitors against devr-mediated dormancy of mycobacterium tuberculosis.bacterial persistence is the hallmark of tuberculosis (tb) and poses the biggest threat to the success of any antitubercular drug regimen. the devr/dosr dormancy regulator of mycobacterium tuberculosis belongs to the narl subfamily of response regulators and is essential for m. tuberculosis persistence in macaque models of tb. the devr/dosr crystal structure revealed a unique (αβ)4 topology instead of the classical (αβ)5 structure found in the receiver domain of other regulators in this subfamil ...201628043637
development of escherichia coli and mycobacterium smegmatis recombinants expressing major mycobacterium tuberculosis-specific antigenic proteins.mycobacterium tuberculosis is an obligate pathogenic bacterial species in the family mycobacteriaceae and the causative agent of most tuberculosis (tb) cases. until today, the only approved tb vaccine is bacille calmette guerin (bcg), which has been used since 1921. while bcg provides fairly effective protection for infants and young children, its efficacy in adults is variable around the world. this could be due to several parameters including strains of the vaccine and exposure of individuals ...201628043633
evaluation of specific antibodies against mycobacterium tuberculosis recombinant antigens for detection of recent infection.since an accurate test for detection of mycobacterium tuberculosis early infection is urgently needed, this study was designed for development of an efficient screening test in diagnosis of tuberculosis infection.201628043591
cloning, expression, and purification of recombinant protein mpt-64 from a virulent strain of mycobacterium bovis in a prokaryotic system.tuberculosis (tb) is a zoonotic infectious disease common to humans and animals that is caused by the rod-shaped acid-fast bacterium mycobacterium bovis. rapid and sensitive detection of tb is promoted by specific antigens. virulent strains of the tb complex from m. bovis contain 16 regions of difference (rd) in their genome that encode important proteins, including major protein of mycobacterium tuberculosis 64 (mbt-64, which is a primary immune-stimulating antigen encoded by rd-2. in this stud ...201628043587
effects of sorbitol and glycerol on the structure, dynamics, and stability of mycobacterium tuberculosis pyrazinamidase.mycobacterium tuberculosis pyrazinamidase (pzase) is known an enzyme that is involved in degradation of pyrazinamide to ammonia and pyrazinoic acid. pyrazinamide is an important first-line drug used in the short-course treatment of tuberculosis. previous investigations have indicated that the pyrazinamide (pza)-resistant m. tuberculosis strains are caused by point mutations in the pzase enzyme which is the activator of the prodrug pza. although the general fold of pzase was determined, the struc ...201628043510
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
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
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
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 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 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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