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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
balancing trained immunity with persistent immune activation and the risk of simian immunodeficiency virus infection in infant macaques vaccinated with attenuated mycobacterium tuberculosis or mycobacterium bovis bcg vaccine.our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (hiv-1) and tuberculosis (tb) infections. the vaccine consists of an auxotroph mycobacterium tuberculosis strain that coexpresses hiv antigens. utilizing an infant rhesus macaque model, we have previously shown that this attenuated m. tuberculosis (amtb)-simian immunodeficiency virus (siv) vaccine is immunogenic, and although the vaccine did not prevent o ...201727655885
trained immunity and susceptibility to hiv.in this issue of clinical and vaccine immunology, k. jensen et al. (clin vaccine immunol 24:e00360-16, 2017, https://doi.org/10.1128/cvi.00360-16) describe a dual-purpose attenuated mycobacterium tuberculosis-simian immunodeficiency virus vaccine (amtb-siv). interestingly, immunized infant macaques required fewer oral exposures to siv to become infected relative to nonimmunized animals. the authors hypothesized that augmented susceptibility to siv was due to activation of cd4(+) t cells through ...201727847369
mycobacterial peritonitis in capd patients in limpopo: a 6-year cumulative report from a single center in south africa.south africa has one of the highest incidences of tuberculosis (tb) worldwide due to the ongoing human immunodeficiency virus (hiv) epidemic. there are, however, no reports on peritonitis in continuous ambulatory peritoneal dialysis (capd) patients due to mycobacterium tuberculosis in south africa. the aim of this study is to discuss our experience of tuberculous peritonitis in capd patients from a rural endemic area of south africa. this is a retrospective descriptive study of capd patients dia ...201727006437
efficacy of resistance to francisella imparted by ity/nramp/slc11a1 depends on route of infection.natural resistance-associated macrophage protein (nramp) encoded by the slc11a1 gene is a membrane-associated transporter of divalent metal ions. murine slc11a1 has two known alleles, a functional slc11a1(gly169), which is found in dba2/j, nod/ltj, and 129p3/j and related mouse strains, and a non-functional slc11a1(asp169), that is found in c56bl/6j (b6) and balb/cj mice. b6 mice congenic for slc11a1(gly169) (b6-slc11a1(g169) ) are markedly resistant to the intracellular pathogens salmonella, le ...201728360906
influence of socio-economic inequality measured by the gini coefficient on meningitis incidence caused by mycobacterium tuberculosis and haemophilus influenzae in colombia, 2008-2011.bacterial meningitis is an important cause of infectious neurological morbidity and mortality. its incidence has decreased with the introduction of vaccination programmes against preventable agents. however, low-income and middle-income countries with poor access to health care still have a significant burden of the disease. thus, the relationship between the gini coefficient and h. influenzae and m. tuberculosis meningitis incidence in colombia, during 2008-2011, was assessed. in this ecologica ...201728353449
discovery of anti-microbial and anti-tubercular molecules from fusarium solani: an endophyte of glycyrrhiza glabra.glycyrrhiza glabra is a high-value medicinal plant thriving in biodiversity rich kashmir himalaya. the present study was designed to explore the fungal endophytes from g. glabra as a source of bioactive molecules.201728150900
[coinfection of mycobacterium malmoense and mycobacterium tuberculosis in a patient with acquired inmune deficiency syndrome].a case is presented of coinfection with mycobacterium malmoense and mycobacterium tuberculosis in a cuban patient with aids which produced respiratory and liver disease respectively. cultures done from sputum samples showed the presence of a non-pigmented, slow growing mycobacterial strain belonging to runyon group iii and identified as mycobacterium malmoense. from cultures of liver tissue removed laparoscopically, a strain was isolated and subsequently identified as mycobacterium tuberculosis. ...201725597735
mycobacterium marinum.mycobacterium marinum is a well-known pathogenic mycobacterium for skin and soft tissue infections and is associated with fishes and water. among nontuberculous mycobacteria (ntm), it is the leading cause of extrarespiratory human infections worldwide. in addition, there is a specific scientific interest in m. marinum because of its genetic relatedness to mycobacterium tuberculosis and because experimental infection of m. marinum in fishes mimics tuberculosis pathogenesis. microbiological charac ...201728387180
regulation of phagocyte triglyceride by a stat-atg2 pathway controls mycobacterial infection.mycobacterium tuberculosis remains a global threat to human health, yet the molecular mechanisms regulating immunity remain poorly understood. cytokines can promote or inhibit mycobacterial survival inside macrophages and the underlying mechanisms represent potential targets for host-directed therapies. here we show that cytokine-stat signalling promotes mycobacterial survival within macrophages by deregulating lipid droplets via atg2 repression. in drosophila infected with mycobacterium marinum ...201728262681
functional characterisation of the drosophila cg6568 gene in host defence against mycobacterium marinum.mycobacterium marinum is a pathogenic mycobacterial species closely related to mycobacterium tuberculosis. in this study, we established a mycobacterial infection model of drosophila melanogaster to characterize the role played by cg6568, a homolog of the human cathelicidin gene, in the innate defense against infection. drosophila cg6568 was expressed at various levels during all developmental stages, and the expression levels were modulated by m. marinum in a time-dependent manner. 20-hydroxyec ...201728245983
mycobacterial esx-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions.mycobacterium tuberculosis and mycobacterium marinum are thought to exert virulence, in part, through their ability to lyse host cell membranes. the type vii secretion system esx-1 [6-kda early secretory antigenic target (esat-6) secretion system 1] is required for both virulence and host cell membrane lysis. both activities are attributed to the pore-forming activity of the esx-1-secreted substrate esat-6 because multiple studies have reported that recombinant esat-6 lyses eukaryotic membranes. ...201728119503
murine mycobacterium marinum infection as a model for tuberculosis.mycobacteria are a major human health problem globally. regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (manjelievskaia j et al, trans r soc trop med hyg 110: 110, 2016; pereira et al., lancet infect dis 12:300-306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-prevention and available treatments. thus, increased basic understanding of mycobacterial-and particularly ...201727914088
screening of anti-mycobacterial compounds in a naturally infected zebrafish larvae model.mycobacterium tuberculosis is a deadly human pathogen that causes the lung disease tb. m. tuberculosis latently infects a third of the world's population, resulting in ∼1.5 million deaths per year. due to the difficulties and expense of carrying out animal drug trials using m. tuberculosis and rodents, infections of the zebrafish danio rerio with mycobacterium marinum have become a useful surrogate. however, the infection methods described to date require specialized equipment and a high level o ...201727798206
mycobacterium tuberculosis peptidyl-prolyl isomerases are immunogenic, alter cytokine profile and aid in intracellular survival.mycobacterium tuberculosis (m. tb) has two peptidyl-prolyl isomerases (ppiases) ppia and ppib, popularly known as cyclophilin a and cyclophilin b. the role of cyclophilins in processes such as signaling, cell surface recognition, chaperoning, and heat shock response has been well-documented. we present evidence that m. tb ppiases modulate the host immune response. elisa results revealed significant presence of antibodies to m. tb ppiases in patient sera as compared to sera from healthy individua ...201728261567
heparin-binding hemagglutinin of mycobacterium tuberculosis is an inhibitor of autophagy.airway epithelial cell is often the initial site of attack by pathogens, and cell death is commonly caused by internalization of mycobacterium tuberculosis (mtb). however, the mechanism of interaction between epithelial cells and mtb is not well understood. in this study, we investigated the role of the heparin-binding hemagglutinin (hbha) protein of mtb in the function of epithelial cells. in particular, the autophagy of a549 cells was determined based on microtubule-associated protein 1 light ...201728224118
mycobacterium tuberculosis rv1987 induces th2 immune responses and enhances mycobacterium smegmatis survival in mice.mycobacterium tuberculosis can interfere with host immune response and escape clearance through its specific antigens. m. tuberculosis rv1987 encoded by region of difference (rd)-2 gene is a secretory protein with immunogenic potency. here, we investigated the impact of rv1987 on host cytokine responses and t cell polarization in mouse aerosol model. a recombinant m. smegmatis mc(2)155 strain that overexpressed rv1987 protein (named ms1987) was constructed and used to infect c57bl/6 mice. the mc ...201728219528
molecular characterization of a new gene cluster for steroid degradation in mycobacterium smegmatis.the c-19 steroids 4-androstene-3,17-dione (ad), 1,4-androstadiene-3,17-dione (add) or 9α-hydroxy-4-androstene-3,17-dione (9oh-ad), which have been postulated as intermediates of the cholesterol catabolic pathway in mycobacterium smegmatis, cannot be used as sole carbon and energy sources by this bacterium. only the δkstr mutant which constitutively expresses the genes repressed by the kstr regulator can metabolize ad and add with severe difficulties but still cannot metabolize 9oh-ad, suggesting ...201728217856
mycobacterium tuberculosis esxl inhibit mhc-ii expression by promoting hypermethylation in class-ii transactivator loci in macrophages.mycobacterium tuberculosis (mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. one of the key mechanisms includes repression of class-ii transactivator (ciita) and mhc-ii expression in infected macrophages. however, the precise mechanism of ciita and mhc-ii down-regulation is not well studied. mtb 6-kda early secretory antigenic target (esat-6) is a known potent virulence and antigenic determinant. mtb genome encodes 23 such esat-6 family pro ...201728209712
the influence of accd5 on accd6 carboxyltransferase essentiality in pathogenic and non-pathogenic mycobacterium.malonyl-coenzyme a (coa) is a crucial extender unit for the synthesis of mycolic and other fatty acids in mycobacteria, generated in a reaction catalyzed by acetyl-coa carboxylase. we previously reported on the essentiality of accd6mtb encoding the functional acetyl-coa carboxylase subunit in mycobacterium tuberculosis. strikingly, the homologous gene in the fast-growing, non-pathogenic mycobacterium smegmatis - (accd6msm) appeared to be dispensable, and its deletion did not influence the cell l ...201728205597
down-regulation of pe11, a cell wall associated esterase, enhances the biofilm growth of mycobacterium tuberculosis and reduces cell wall virulence lipid levels.pe11 (rv1169c or lipx) is a cell wall associated esterase/lipase of mycobacterium tuberculosis (mtb). evidences suggest that pe11 is expressed by mtb both in vitro and in vivo. previous studies have shown that pe11 leads to modification in cell wall lipid content and enhanced virulence when expressed in the non-pathogenic surrogate mycobacterium smegmatis. since cell wall lipids often play different roles in pathogenic and non-pathogenic mycobacteria, we investigated the role of pe11 in its host ...201728198348
identification of a membrane protein required for lipomannan maturation and lipoarabinomannan synthesis in corynebacterineae.mycobacterium tuberculosis and related corynebacterineae synthesize a family of lipomannans (lm) and lipoarabinomannans (lam) that are abundant components of the multilaminate cell wall and essential virulence factors in pathogenic species. here we describe a new membrane protein, highly conserved in all corynebacterineae, that is required for synthesis of full-length lm and lam. deletion of the corynebacterium glutamicum ncgl2760 gene resulted in a complete loss of mature lm/lam and the appeara ...201728167532
double mutation in dna gyrase confers moxifloxacin resistance and decreased fitness of mycobacterium smegmatis.ofloxacin and moxifloxacin are the most commonly used fluoroquinolones (fqs) for the treatment of tuberculosis. as a new generation fq, moxifloxacin has been recommended for the treatment of ofloxacin-resistant tb. however, the mechanism by which ofloxacin-resistant mycobacterium tuberculosis further gains resistance to moxifloxacin remains unclear.201728387828
mycobacterial cultures contain cell size and density specific sub-populations of cells with significant differential susceptibility to antibiotics, oxidative and nitrite stress.the present study shows the existence of two specific sub-populations of mycobacterium smegmatis and mycobacterium tuberculosis cells differing in size and density, in the mid-log phase (mlp) cultures, with significant differential susceptibility to antibiotic, oxidative, and nitrite stress. one of these sub-populations (~10% of the total population), contained short-sized cells (scs) generated through highly-deviated asymmetric cell division (acd) of normal/long-sized mother cells and symmetric ...201728377757
catabolism of the last two steroid rings in mycobacterium tuberculosis and other bacteria.most mycolic acid-containing actinobacteria and some proteobacteria use steroids as growth substrates, but the catabolism of the last two steroid rings has yet to be elucidated. in mycobacterium tuberculosis, this pathway includes virulence determinants and has been proposed to be encoded by the kstr2-regulated genes, which include a predicted coenzyme a (coa) transferase gene (ipdab) and an acyl-coa reductase gene (ipdc). in the presence of cholesterol, δipdc and δipdab mutants of either m. tub ...201728377529
ppe38 protein of mycobacterium tuberculosis inhibits macrophage mhc class i expression and dampens cd8(+) t cell responses.suppression of cd8(+) t cell activation is a critical mechanism used by mycobacterium tuberculosis (mtb) to escape protective host immune responses. ppe38 belongs to the unique ppe family of mtb and in our previous study, ppe38 protein was speculated to participate in manipulating macrophage mhc class i pathway. to test this hypothesis, the function of mycobacterial ppe38 protein was assessed here using macrophage and mouse infection models. decreased amount of mhc class i was observed on the su ...201728348981
tetrahydro-2-furanyl-2,4(1h,3h)-pyrimidinedione derivatives as novel antibacterial compounds against mycobacterium.mycobacterium tuberculosis thymidine monophosphate kinase (mttmpk) is a potential enzymatic target for the treatment of tuberculosis (tb).201728317807
genome-wide transposon mutagenesis in mycobacterium tuberculosis and mycobacterium smegmatis.tnseq, or transposon (tn) insertion sequencing, is a powerful method for identifying the essential-as well as conditionally essential-regions in a genome, both coding and noncoding. the advent of accessible massively parallel dna sequencing technologies in particular has resulted in the increased use of tnseq-based approaches to elucidate various aspects of bacterial physiology and metabolism. moreover, the availability of detailed protocols has enabled even nonspecialist laboratories to adapt a ...201727709585
secondary metabolites from tetracera potatoria stem bark with anti-mycobacterial activity.tetracera potatoria afzel. exg. don (dilleniaceae) is a medicinal plant used traditionally in africa for the treatment of tuberculosis related ailments and respiratory infections. the antibacterial activity of the medium polar extracts of t. potatoria leaves and stem bark was recently reported against mycobacterium smegmatis (mic 25µg/ml) and m. aurum (65µg/ml), two fast-growing mycobacterium strains used as model micro-organisms for the more pathogenic strain mycobacterium tuberculosis (fomogne ...201727864111
mycobacterial phenolic glycolipid synthesis is regulated by camp-dependent lysine acylation of fadd22.the mycobacterial cell envelope is unique in its chemical composition, and has an important role to play in pathogenesis. phthiocerol dimycocerosates (pdims) and glycosylated phenolphthiocerol dimycocerosates, also known as phenolic glycolipids (pgls), contribute significantly to the virulence of mycobacterium tuberculosis. fadd22 is essential for pgl biosynthesis. we have recently shown in vitro that fadd22 is a substrate for lysine acylation by a unique camp-dependent, protein lysine acyltrans ...201728141495
diverse effects of mycobacterial proline-proline-glutamic acid proteins upon interaction with host macrophages.the proline-proline-glutamic acid (ppe) family proteins are abundant only in pathogenic mycobacteria, but their general functions are far from unveiled. to investigate their roles in how mycobacterium tuberculosis (mtb) resists killing by the host, 25 ppe recombinant mycobacterium smegmatis strains that overexpress mtb ppe proteins were constructed. during phagocytosis, a similar amount of intracellular bacteria was observed at 2 h post-infection (hpi) for 24 ppe recombinants, while a 50% reduct ...201728130364
assessment of metabolic changes in mycobacterium smegmatis wild-type and alr mutant strains: evidence of a new pathway of d-alanine biosynthesis.in mycobacteria, d-alanine is an essential precursor for peptidoglycan biosynthesis. the only confirmed enzymatic pathway to form d-alanine is through the racemization of l-alanine by alanine racemase (alr, ec 5.1.1.1). nevertheless, the essentiality of alr in mycobacterium tuberculosis and mycobacterium smegmatis for cell survivability in the absence of d-alanine has been a point of controversy with contradictory results reported in the literature. to address this issue, we examined the effects ...201728121156
identification of mycobacterial rplj/l10 and rpsa/s1 proteins as novel targets for cd4(+) t cells.tuberculosis (tb) due to mycobacterium tuberculosis remains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for the control and prevention of disease caused by this organism. we previously reported that a genetically modified strain of mycobacterium smegmatis called ikeplus is a promising tb vaccine candidate. since protective immunity induced by ikeplus is dependent on antigen-specific cd4(+) t cell memory, we hypothesized that the specificity of the ...201728115505
prophage-mediated defence against viral attack and viral counter-defence.temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. mycobacteriophages are viruses that infect mycobacterial hosts including mycobacterium tuberculosis and mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. characterization of ten cluster n temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that ...201728067906
vitamin c targets (p)ppgpp synthesis leading to stalling of long-term survival and biofilm formation in mycobacterium smegmatis.earlier, vitamin c was demonstrated to sterilize mycobacterium tuberculosis culture via fenton's reaction at high concentration. it alters the regulatory pathways associated with stress response and dormancy. since (p)ppgpp is considered to be the master regulator of stress response and is responsible for bacterial survival under stress, we tested the effect of vitamin c on the formation of (p)ppgpp. in vivo estimation of (p)ppgpp showed a decrease in (p)ppgpp levels in vitamin c-treated m. smeg ...201727986825
mycobacterium tuberculosis ppe25 and ppe26 proteins expressed in mycobacterium smegmatis modulate cytokine secretion in mouse macrophages and enhance mycobacterial survival.ppe25 and ppe26, the mycobacterium tuberculosis proline-proline-glutamic acid (ppe) family proteins, are members of the m. tuberculosis esx-5 system associated with virulence of m. tuberculosis. to investigate the roles of ppe25 and ppe26 during m. tuberculosis infection, we expressed them in non-pathogenic fast-growing mycobacterium smegmatis, respectively, and used these recombinant strains to infect ana-1 macrophages and balb/c mice. we observed that both ppe25 and ppe26 enhanced survival of ...201727351106
antibiotic bactericidal activity is countered by maintaining ph homeostasis in mycobacterium smegmatis.antibiotics target specific biosynthetic processes essential for bacterial growth. it is intriguing that several commonalities connect the bactericidal activity of seemingly disparate antibiotics, such as the numerous conditions that confer broad-spectrum antibiotic tolerance. whether antibiotics kill in a manner unique to their specific targets or by a universal mechanism is a critical and contested subject. herein, we demonstrate that the bactericidal activity of diverse antibiotics against my ...201727579369
genomic characterization of nontuberculous mycobacteria.mycobacterium tuberculosis and mycobacterium leprae have remained, for many years, the primary species of the genus mycobacterium of clinical and microbiological interest. the other members of the genus, referred to as nontuberculous mycobacteria (ntm), have long been underinvestigated. in the last decades, however, the number of reports linking various ntm species with human diseases has steadily increased and treatment difficulties have emerged. despite the availability of whole genome sequenc ...201728345639
rifz (amed_0655) is a pathway-specific regulator for rifamycin biosynthesis in amycolatopsis mediterranei.rifamycin and its derivatives are particularly effective against the pathogenic mycobacteria mycobacterium tuberculosis and mycobacterium leprae although the biosynthetic pathway of rifamycin has been extensively studied in amycolatopsis mediterranei, little is known about the regulation in rifamycin biosynthesis. here, an in vivo transposon system was employed to identify genes involved in the regulation of rifamycin production in a. mediterranei u32. in total, nine rifamycin-deficient mutants ...201728159794
multiple nontuberculous scrofulodermas showing dramatic response to clarithromycin.atypical mycobacteria are distinct from the mycobacterium tuberculosis. mycobacterium chelonae, a non-pigment producing rapid grower, can be found in many cutaneous sites; infection occurs most commonly after skin trauma from surgery, injections, or minor injuries. in immune competent patients, the infection is more frequently localized as a cellulitis or a nodule, whereas, in the immunocompromised patient, dissemination (more than five lesions) can occur. because the organism is resistant to an ...201725657914
mycobacterium kansasii infection in a patient receiving biologic therapy-not all reactive interferon gamma release assays are tuberculosis.mycobacterium kansasii, a nontuberculous mycobacterium, can lead to lung disease similar to tuberculosis. immunotherapeutic biologic agents predispose to infections with mycobacteria, including m kansasii. t-cell-mediated interferon gamma release assays like quantiferon-tb gold test (qft) are widely used by clinicians for the diagnosis of infections with mycobacterium tuberculosis; however, qft may also show positive result with certain nontuberculous mycobacterial infections. we report a case o ...201728317629
mycobacterium kansasii.the incidence of mycobacterium kansasii varies widely over time and by region, but this organism remains one of the most clinically relevant isolated species of nontuberculous mycobacteria. in contrast to other common nontuberculous mycobacteria, m. kansasii is infrequently isolated from natural water sources or soil. the major reservoir appears to be tap water. infection is likely acquired through the aerosol route, with low infectivity in regions of endemicity. human-to-human transmission is t ...201728185617
pulmonary mycobacterium kansasii disease in immunocompetent host: treatment outcomes with short-course chemotherapy.mycobacterium kansasii, most virulent of all atypical mycobacteria, causes pulmonary disease identical to the disease caused by mycobacterium tuberculosis. early identification of the species and prompt initiation of treatment for m. kansasii is necessary to prevent morbidity and mortality due to this disease. this case series highlights the similarity in the clinical presentation of both m. tuberculosis and m. kansasii and response to direct observation of short-course chemotherapy with rifampi ...201727934834
diagnosis and implications of mycobacterium bovis infection in banded mongooses (mungos mungo) in the kruger national park, south africa.bovine tuberculosis (btb) was first diagnosed in the kruger national park (knp) in 1990. research has since focused on the maintenance host, the african buffalo ( syncerus caffer ) and clinically affected lion ( panthera leo ). however, little is known about the role of small predators in tuberculosis epidemiology. during 2011-12, we screened banded mongooses ( mungos mungo ) in the btb high-prevalence zone of the knp for mycobacterium tuberculosis complex members. fecal swabs, tracheal swabs, a ...201727788055
mycobacterium bovis requires p27 (lprg) to arrest phagosome maturation and replicate within bovine macrophages.mycobacterium bovis causes tuberculosis in a wide variety of mammals, with strong tropism for cattle and eventually humans. p27, also called lprg, is among the proteins involved in the mechanisms of the virulence and persistence of m. bovis and mycobacterium tuberculosis here, we describe a novel function of p27 in the interaction of m. bovis with its natural host cell, the bovine macrophage. we found that a deletion in the p27-p55 operon impairs the replication of m. bovis in bovine macrophages ...201728031264
molecular and genomic features of mycobacterium bovis strain 1595 isolated from korean cattle.the aim of this study was to investigate the molecular characteristics and conduct a comparative genomic analysis for mycobacterium bovis strain 1595 isolated from a native korean cow. molecular typing showed that m. bovis 1595 has spoligotype sb0140 with mycobacterial interspersed repetitive units-variable number of tandem repeats typing of 4-2-5-3-2-7-5-5-4-3-4-3-4-3, representing the most common type of m. bovis in korea. the complete genome sequence of strain 1595 was determined using illumi ...201728385004
the bioinformatics analysis of comparative genomics of mycobacterium tuberculosis complex (mtbc) provides insight into dissimilarities between intraspecific groups differing in host association, virulence, and epitope diversity.tuberculosis now exceeds hiv as the top infectious disease cause of mortality, and is caused by the mycobacterium tuberculosis complex (mtbc). mtbc strains have highly conserved genome sequences (similarity >99%) but dramatically different phenotypes. to analyze the relationship between genotype and phenotype, we conducted the comparative genomic analysis on 12 mtbc strains representing different lineages (i.e., mycobacterium bovis; m. bovis bcg; m. microti; m. africanum; m. tuberculosis h37rv; ...201728377903
delamanid kills dormant mycobacteria in vitro and in the guinea pig model of tuberculosis.tb treatment is long and requires multiple drugs, likely due to various phenotypes of tb bacilli with variable drug-susceptibility. drugs with broad activity are urgently needed. the study aimed to evaluate delamanid's activity against growing or dormant bacilli in vitro as well as in vivo culture of mycobacterium bovis bcg tokyo under aerobic and anaerobic condition was used to study delamanid's activity against growing and dormant bacilli, respectively. delamanid exhibited significant bacteric ...201728373190
proteomic analysis of protein purified derivative of mycobacterium bovis.tuberculin skin test based on in vivo intradermal inoculation of purified protein derivative from mycobacterium bovis (bppd) is the diagnostic test for the control and surveillance of bovine tuberculosis (btb).201728372590
comparative proteomics analysis of human macrophages infected with virulent mycobacterium bovis.mycobacterium bovis (m. bovis), the most common pathogens of tuberculosis (tb), is virulent to human and cattle, and transmission between cattle and humans warrants reconsideration concerning food safety and public health. recently, efforts have begun to analyze cellular proteomic responses induced by mycobacterium tuberculosis (m. tb). however, the underlying mechanisms by which virulent m. bovis affects human hosts are not fully understood. for the present study, we utilized a global and compa ...201728337427
mycobacterial caseinolytic protease gene regulator clgr is a substrate of caseinolytic protease.the mycobacterial caseinolytic protease clpp1p2 is a degradative protease that recently gained interest as a genetically and pharmacologically validated drug target for tuberculosis. the first whole-cell active clpp1p2 inhibitor, the human proteasome inhibitor bortezomib, is currently undergoing lead optimization to introduce selectivity for the bacterial target. how inhibition of clpp1p2 translates into whole-cell antimicrobial activity is little understood. previous work has shown that the cas ...201728317028
recombinant bcg expressing esx-1 of mycobacterium marinum combines low virulence with cytosolic immune signaling and improved tb protection.recent insights into the mechanisms by which mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. the only licensed anti-tuberculosis vaccine, mycobacterium bovis bcg, provides limited protection. a feature of bcg is the partial deletion of the esx-1 type vii secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked t ...201728297677
same-day diagnostic and surveillance data for tuberculosis via whole genome sequencing of direct respiratory samples.routine full characterization of mycobacterium tuberculosis (tb) is culture-based, taking many weeks. whole-genome sequencing (wgs) can generate antibiotic susceptibility profiles to inform treatment, augmented with strain information for global surveillance; such data could be transformative if provided at or near point of care.we demonstrate a low-cost dna extraction method for tb wgs direct from patient samples. we initially evaluated the method using the illumina miseq sequencer (40 smear-po ...201728275074
rationalized design of a mucosal vaccine protects against mycobacterium tuberculosis challenge in mice.pulmonary tuberculosis (tb) caused by mycobacterium tuberculosis (mtb) is a leading cause of global morbidity and mortality. the only licensed tb vaccine, mycobacterium bovis bacillus calmette-guerin (bcg), has variable efficacy in protecting against pulmonary tb. thus, the development of more effective tb vaccines is critical to control the tb epidemic. specifically, vaccines delivered through the mucosal route are known to induce th17 responses and provide superior protection against mtb infec ...201728258153
tlr2 contributes to trigger immune response of pleural mesothelial cells against mycobacterium bovis bcg and m. tuberculosis infection.mycobacterium tuberculosis is a causative agent leading to pleural effusion, characterized by the accumulation of fluid and immune cells in the pleural cavity. although this phenomenon has been described before, detailed processes or mechanisms associated with the pleural effusion are still not well understood. pleural mesothelial cells (pmcs) are specialized epithelial cells that cover the body wall and internal organs in pleural cavity playing a central role in pleural inflammation. toll-like ...201728249177
comparison of sputum-culture conversion for mycobacterium bovis and m. tuberculosis.current us guidelines recommend longer treatment for tuberculosis (tb) caused by pyrazinamide-resistant organisms (e.g., mycobacterium bovis) than for m. tuberculosis tb. we compared treatment response times for patients with m. bovis tb and m. tuberculosis tb reported in the united states during 2006-2013. we included culture-positive, pulmonary tb patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. time to sputum-culture conversion was defined as t ...201728221125
epidemiology of mycobacterium bovis disease in humans in england, wales, and northern ireland, 2002-2014.despite control efforts, mycobacterium bovis incidence among cattle remains high in parts of england, wales, and northern ireland, attracting political and public health interest in potential spread from animals to humans. to determine incidence among humans and to identify associated factors, we conducted a retrospective cohort analysis of human m. bovis cases in england, wales, and northern ireland during 2002-2014. we identified 357 cases and observed increased annual case numbers (from 17 to ...201728220748
a novel mycobacterial in vitro infection assay identifies differences of induced macrophage apoptosis between cd4+ and cd8+ t cells.macrophages are natural host cells for pathogenic mycobacteria, like mycobacterium tuberculosis (m.tb). immune surveillance by t cells and interaction with m.tb infected macrophages is crucial for protection against m.tb reactivation and development of active tuberculosis. several factors play a role in the control of m.tb infection but reliable biomarkers remain elusive. one major obstacle is the absence of functional in vitro assays which allow concomitant determination of i) mycobacterial era ...201728199374
molecular detection of m. tuberculosis and m. bovis and hematological and biochemical analyses in agricultural sprayers exposed to pesticides: a cross-sectional study in punjab, pakistan during 2014-2016.we determined the correlation between a pesticide exposure, physical health and susceptibility toward tuberculosis along with hematological indices and liver enzymes' alterations in sprayers exposed to pesticides. molecular detection of mycobacterium tuberculosis and mycobacterium bovis was detected by targeting histone-like protein (hupb) gene. the wbc (white blood cells) and rbc (red blood cells) levels of male sprayers and non-sprayers were significantly different (p<0.05). in female spray wo ...201728145400
a novel benzothiazinethione analogue sklb-tb1001 displays potent antimycobacterial activities in a series of murine models.new chemotherapeutic compounds and regimens are needed to combat multidrug-resistant mycobacterium tuberculosis. here, we used a series of murine models to assess an antitubercular lead compound sklb-tb1001. in the mycobacterium bovis bacillus calmette-guérin and the acute m. tuberculosis h37rv infection mouse models, sklb-tb1001 significantly attenuated the mycobacterial load in lungs and spleens. the colony forming unit counts and histological examination of lungs from h37rv infected mice reve ...201728142116
ruptured aortic aneurysm due to mycobacterium bovis bcg with a delayed bacteriological diagnosis due to false negative result of the mpb 64 immunochromatographic assay.adjuvant therapy with bacillus calmette-guerin (bcg), a live attenuated strain of mycobacterium bovis, has become the treatment of choice for low-risk superficial bladder carcinoma following transurethral resection of the bladder. complications following vesical bcg instillations are uncommon but, in some cases, severe side-effects can occur such as sepsis or mycotic aneurysm. besides usual laboratory techniques used for the diagnosis of mycobacterium tuberculosis complex (mtbc) infections (smea ...201728126017
quinolidene based monocarbonyl curcumin analogues as promising antimycobacterial agents: synthesis and molecular docking study.a series of quinoline incorporated monocarbonyl curcumin analogues was efficiently synthesized using [hdbu][hso4] as catalyst via knoevenagel type condensation and evaluated for their in vitro antitubercular activity against mycobacterium tuberculosis h37ra (mtb) and mycobacterium bovis bcg in dormant state. the analogues 3e, 3h, 4a and 4e exhibited very good antitubercular activity. the antiproliferative activity of the analogues against mcf-7, a549 and hct-116 cell lines was evaluated using mo ...201728110868
esx-1 and phthiocerol dimycocerosates of mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis.although phthiocerol dimycocerosates (dim) are major virulence factors of mycobacterium tuberculosis (mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. localized in the outer membrane of mycobacterial pathogens, dim are predicted to interact with host cell membranes. interaction with eukaryotic membranes is a property shared with another virulence factor of mtb, the early secretory antigenic target esxa (also known as esat-6). this small protein, w ...201728095608
ocular mycobacteriosis-dual infection of m. tuberculosis complex with m. fortuitum and m. bovis.we report unfavorable outcome in a patient with subretinal granuloma caused by dual infection of mycobacterium tuberculosis complex with mycobacterium fortuitum and mycobacterium bovis in an immunosuppressed, non-hiv patient. we did a systematic review of literature on dual infection due to m. tuberculosis and m. fortuitum via medline and pubmed and could not find any case reported of causing this kind of dual infection in the eye.201728091937
evaluation of five serologic assays for bovine tuberculosis surveillance in domestic free-range pigs from southern spain.in countries where bovine tuberculosis (btb) is still prevalent the contact among different animal species in extensive systems contributes to the circulation of mycobacterium bovis (m. bovis) and other members of the mycobacterium tuberculosis complex (mtc). thus, free-range pigs can develop subclinical infections and may contribute to disease spread to bovine and wildlife. serodiagnosis has been proposed as a screening tool for detecting infected pig herds; however, the value of this method to ...201728089289
quinolidene-rhodanine conjugates: facile synthesis and biological evaluation.a series of rhodanine incorporated quinoline derivatives were efficiently synthesized using reusable dbu acetate as ionic liquid and evaluated for their in vitro antitubercular activity against mycobacterium tuberculosis h37ra (mtb) (atcc 25177) and mycobacterium bovis bcg (atcc 35743) both in active and dormant state. compounds 3e, 3f, 3g, 3h and 3i exhibited very good antitubercular activity. the active compounds were studied for cytotoxicity against huvec, thp-1, macrophages, a549, panc-1 and ...201727688192
infection by mycobacterium bovis in a dog from brazil.tuberculosis (tb) is a chronic disease caused by bacteria belonging to the mycobacterium tuberculosis complex (mtbc). this disease rarely affects dogs. canine infections are usually caused by m. tuberculosis. mycobacterium bovis infections are rare in dogs and associated with consumption of raw milk or contaminated products. here, we report a boxer dog who had a m. bovis infection and was admitted to a brazilian veterinary hospital with a presumptive diagnosis of chronic ehrlichiosis. despite re ...201727914739
long-chain fatty acyl coenzyme a ligase fadd2 mediates intrinsic pyrazinamide resistance in mycobacterium tuberculosis.pyrazinamide (pza) is a first-line tuberculosis (tb) drug that has been in clinical use for 60 years yet still has an unresolved mechanism of action. based upon the observation that the minimum concentration of pza required to inhibit the growth of mycobacterium tuberculosis is approximately 1,000-fold higher than that of other first-line drugs, we hypothesized that m. tuberculosis expresses factors that mediate intrinsic resistance to pza. to identify genes associated with intrinsic pza resista ...201727855077
zoonotic tuberculosis in human beings caused by mycobacterium bovis-a call for action.mycobacterium tuberculosis is recognised as the primary cause of human tuberculosis worldwide. however, substantial evidence suggests that the burden of mycobacterium bovis, the cause of bovine tuberculosis, might be underestimated in human beings as the cause of zoonotic tuberculosis. in 2013, results from a systematic review and meta-analysis of global zoonotic tuberculosis showed that the same challenges and concerns expressed 15 years ago remain valid. these challenges faced by people with z ...201727697390
development of one-tube multiplex polymerase chain reaction (pcr) for detecting mycobacterium bovis.a multiplex pcr (m-pcr) with primers targeting the 16s rrna, rv3873 and a 12.7-kb fragment in the genomes of a mycobacterium tuberculosis complex was designed for the differential diagnosis of m. tuberculosis, m. bovis, m. bovis bcg and non-tuberculosis mycobacterium (ntm). the specificity of this assay was 100%, and the detection limit was 15 pg of genomic dna. of the 206 blinded clinical samples, the detection rate of m. bovis infection by m-pcr was lower than that of the interferon gamma (ifn ...201727534910
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
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
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
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
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
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
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
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
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
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
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