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lipids in infectious diseases - the case of aids and tuberculosis.lipids play a central role in many infectious diseases. aids (acquired immune deficiency syndrome) and tuberculosis are two of the deadliest infectious diseases to have struck mankind. the pathogens responsible for these diseases, human immunodeficiency virus-1 and mycobacterium tuberculosis, rely on lipids and on lipid membrane properties to gain access to their host cells, to persist in them and ultimately to egress from their hosts. in this review, we discuss the life cycles of these pathogen ...201728535936
matrix degradation in human immunodeficiency virus type 1-associated tuberculosis and tuberculosis immune reconstitution inflammatory syndrome: a prospective observational study.extensive immunopathology occurs in human immunodeficiency virus (hiv)/tuberculosis (tb) coinfection, but the underlying molecular mechanisms are not well-defined. excessive matrix metalloproteinase (mmp) activity is emerging as a key process but has not been systematically studied in hiv-associated tb.201728475709
human leukocyte antigen class i (a, b and c) allele and haplotype variation in a south african mixed ancestry population.south africa has a large (∼53million), ethnically diverse population (black african, caucasian, indian/asian and mixed ancestry) and a high disease burden (particularly hiv-1 and mycobacterium tuberculosis). the mixed ancestry population constitutes ∼9% of the total population and was established ∼365years ago in the western cape region through interracial mixing of black africans, europeans and asians. admixed populations present unique opportunities to identify genetic factors involved in dise ...201728438553
association of tuberculosis status with neurologic disease and immune response in htlv-1 infection.the human t cell lymphotropic virus type 1 (htlv-1) is the etiologic agent of htlv-1-associated myelopathy/tropical spastic paraparesis (ham/tsp). htlv-1 infected individuals have increased susceptibility to mycobacterium tuberculosis infection but the influence of tuberculosis (tb) on the course of htlv-1 infection is unknown. the aim of this study was to evaluate the influence of tb on immunological, virologic, and neurologic features of htlv-1 infection. this is a retrospective analysis of in ...201728540757
recombinant invasive lactococcus lactis carrying a dna vaccine coding the ag85a antigen increases inf-γ, il-6, and tnf-α cytokines after intranasal immunization.tuberculosis (tb) remains a major threat throughout the world and in 2015 it caused the death of 1.4 million people. the bacillus calmette-guérin is the only existing vaccine against this ancient disease; however, it does not provide complete protection in adults. new vaccines against tb are eminently a global priority. the use of bacteria as vehicles for delivery of vaccine plasmids is a promising vaccination strategy. in this study, we evaluated the use of, an engineered invasive lactococcus l ...201728744263
taking control: hijacking of rab gtpases by intracellular bacterial pathogens.intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. to establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. since rab-family gtpases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack rab gtpases dynamics and trafficking functions. one such strategy i ...201728632996
respiratory infections associated with anti-tnfα agents.anti-tnfα agents have proved effective in the treatment of various inflammatory, rheumatologic, dermatologic, and gastrointestinal diseases. severe respiratory tract infections of bacterial or fungal origin have emerged as important complications in patients receiving such treatments. the risk of infection due to anti-tnfα therapy is difficult to assess in these patients who are immunocompromised because of the underlying disease itself and of previous or concomitant immunosuppressive drugs. thi ...201728602386
evaluation of antimycobacterial, leishmanicidal and antibacterial activity of three medicinal orchids of arunachal pradesh, india.the ethnic population of arunachal pradesh uses a number of orchids as such, or in decoction for various ailments. three untapped orchids namely, rhynchostylis retusa, tropidia curculioides and satyrium nepalense, traditionally used in tuberculosis, asthma and cold stage of malaria in folk medicine, were selected for the present study.201728764749
inflammasome and fas-mediated il-1β contributes to th17/th1 cell induction in pathogenic bacterial infection in vivo.cd4(+) th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. recent research has revealed the importance of ifn-γ and il-17 double-producing cd4(+) th cells, termed th17/th1 cells, in the induction of autoimmune and inflammatory diseases. in addition, th17/th1 cells are involved in the regulation of infection caused by the intracellular bacterium mycobacterium tuberculosis in humans. however, the precise mechanism ...201728674179
listeria-vectored vaccine expressing the mycobacterium tuberculosis 30 kda major secretory protein via the constitutively active prfa* regulon boosts bcg efficacy against tuberculosis.a potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective bcg vaccine. here we investigate novel live attenuated recombinant listeria monocytogenes (rlm) vaccines expressing the mycobacterium tuberculosis (mtb) 30 kda major secretory protein (r30/ag85b) (rlm30) as heterologous booster vaccines in animals primed with bcg. using three attenuated lm vectors, rlm ...201728630063
trehalose polyphleates, external cell wall lipids in mycobacterium abscessus, are associated with the formation of clumps with cording morphology, which have been associated with virulence.mycobacterium abscessus is a reemerging pathogen that causes pulmonary diseases similar to tuberculosis, which is caused by mycobacterium tuberculosis. when grown in agar medium, m. abscessus strains generate rough (r) or smooth colonies (s). r morphotypes are more virulent than s morphotypes. in searching for the virulence factors responsible for this difference, r morphotypes have been found to form large aggregates (clumps) that, after being phagocytozed, result in macrophage death. furthermo ...201728790995
development of a one-step multiplex pcr assay for differential detection of major mycobacterium species.the prevalence of tuberculosis continues to be high, and nontuberculous mycobacterial (ntm) infection has also emerged worldwide. moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. here, we developed a one-step multiplex pcr assay using whole-genome analysis and bioinformatics to identify novel molecular targets. the aims of this assay were to (i) discriminate between the mycobacterium tuberculosis complex (mtbc) and n ...201728659320
design, synthesis and evaluation of indole-2-carboxamides with pan anti-mycobacterial activity.current treatment regimens for non-tuberculous mycobacteria (ntm) and tuberculosis (tb) generally require long duration of therapy with multiple drugs, some of which are broad spectrum antibiotics. despite some advances in antimicrobial compounds, there remains a need in therapy for antibiotics with specific mycobacterial targets. it has been shown that mmpl3 is an essential transporter required for the translocation of mycolic acids to the mycobacterial cell envelope. here, we synthesized a ser ...201728545813
significant under expression of the dosr regulon in m. tuberculosis complex lineage 6 in sputum.mycobacterium africanum lineage (l) 6 is an important pathogen in west africa, causing up to 40% of pulmonary tuberculosis (tb). the biology underlying the clinical differences between m. africanum and m. tuberculosis sensu stricto remains poorly understood. we performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human tb, m. tuberculosis l4 and the geographically restricted, m. africanum l6 directly from sputa of 11 hiv-negative tb patients from the gambia wh ...201728454650
distribution of non-tuberculosis mycobacteria strains from suspected tuberculosis patients by heat shock protein 65 pcr-rflp.the genus mycobacterium contains more than 150 species. non-tuberculosis mycobacteria (ntm) often cause extrapulmonary and pulmonary disease. mycobacteria detection at species level is necessary and provides useful information on epidemiology and facilitates successful treatment of patients. this retrospective study aimed to determine the incidence of the ntm isolates and mycobacterium tuberculosis (mtb) in clinical specimens collected from iranian patients during february 2011-december 2013, by ...201728855835
recovery rates of non-tuberculous mycobacteria from clinical specimens are increasing in korean tertiary-care hospitals.non-tuberculous mycobacteria (ntm) are being recognized increasingly as the causative agents of opportunistic infections in humans. this study investigated the epidemiologic trends of ntm recovery from various clinical specimens in 2 korean tertiary-care hospitals. we reviewed the laboratory records of patient samples cultured for mycobacteria between 2009 and 2015 at 2 tertiary-care hospitals in korea. the medical records for patients with positive ntm samples were also reviewed. during the stu ...201728665061
nifurtimox is ineffective against drug-resistant mycobacteria. 201728652235
detection of mycobacteria by culture and dna-based methods in animal-derived food products purchased at spanish supermarkets.mycobacteria include obligate and opportunistic pathogens that cause significant human and animal disease. the burden of tuberculosis has been largely reduced in developed territories but remains a huge problem worldwide. the significance of nontuberculous mycobacteria is growing considerably, especially in developed regions with higher life expectancy and more therapy-related immunosuppressed individuals. due to their robustness mycobacteria can contaminate animal products by direct transmissio ...201728649235
solitary pulmonary caseating granulomas: a 5-year retrospective single-center analysis.solitary pulmonary caseating granulomas (spcgs) are a characteristic type of tuberculomas associated with infection with non-tuberculous mycobacteria (ntm) and other microbes; however, their significance remains unclear. the aim of the present study was to describe the clinical characteristics of patients with spcgs in terms of diagnosis, presence of lung cancer and treatment status. a retrospective analysis of 17 immunocompetent patients with histopathologically confirmed caseating granulomas a ...201728588774
conflicting role of mycobacterium species in multiple sclerosis.mycobacterium is a genus of aerobic and acid-fast bacteria, which include several pathogenic organisms that cause serious diseases in mammals. previous studies have associated the immune response against mycobacteria with multiple sclerosis (ms), a chronic demyelinating disease of the central nervous system with unknown etiology. the role of mycobacteria in the pathological process has been controversial and often conflicting. we provide a detailed review of the mycobacteria that have been linke ...201728579973
analysis of differentially expressed proteins in mycobacterium avium-infected macrophages comparing with mycobacterium tuberculosis-infected macrophages.mycobacterium avium (ma) belongs to the intracellular parasitic bacteria. to better understand how ma survives within macrophages and the different pathogenic mechanisms of ma and mycobacterium tuberculosis (mtb), tandem mass tag (tmt) and liquid chromatography-tandem mass spectrometry (lc-ms/ms) analysis have been used to determine the proteins which are differentially expressed in ma-infected and mtb-infected macrophages. 369 proteins were found to be differentially expressed in ma-infected ce ...201728573139
multiplex pcr-based detection of mycobacterium tuberculosis and mycobacterium avium in a single host: one coloniser or dual infection? 201728546234
identification of novel seroreactive antigens in johne's disease cattle by using the mycobacterium tuberculosis protein array.johne's disease, a chronic gastrointestinal inflammatory disease caused by mycobacterium avium subspecies paratuberculosis, is endemic in dairy cattle and other ruminants worldwide and remains a challenge to diagnose using traditional serological methods. given the close phylogenetic relationship between m. avium subsp. paratuberculosis and the human pathogen mycobacterium tuberculosis, here, we applied a whole-proteome m. tuberculosis protein array to identify seroreactive and diagnostic m. avi ...201728515134
an association between pulmonary mycobacterium avium-intracellulare complex infections and biomarkers of th2-type inflammation.the rising incidence of pulmonary mycobacterium avium-intracellulare complex (mai) infection is unexplained but parallels the growing world-wide epidemic of allergic disease. we hypothesized an association between pulmonary mai infection and th2-type immune responses as seen in allergy.201728506264
non-tuberculous mycobacteria. an emerging threat?non-tuberculous mycobacteria (ntm) isolates are becoming more common. the main objective of our study was to establish the number and diversity of ntm species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates.201728433210
complications of chronic necrotizing pulmonary aspergillosis: review of published case reports.chronic necrotizing pulmonary aspergillosis (cnpa), a form of chronic pulmonary aspergillosis (cpa), affects immunocompetent or mildly immunocompromised persons with underlying pulmonary disease. these conditions are associated with high morbidity and mortality and often require long-term antifungal treatment. the long-term prognosis for patients with cnpa and the potential complications of cnpa have not been well documented. the aim of this study was to review published papers that report cases ...201728423094
non-pnca gene-mutated but pyrazinamide-resistant mycobacterium tuberculosis: why is that?pyrazinamide (pza) is a key component for the effective treatment of drug-susceptible and pza-susceptible multidrug-resistant (mdr(pza-s)) tuberculosis (tb). pnca gene mutations are usually detected in a clear majority (>90%) of pza-resistant strains but obviously not in all. rapid and reliable pza drug susceptibility testing (dst) is critical whenever pza is to be used in a treatment regimen, not least for the treatment of mdr(pza-s) tb. in this study, we selected 26 pza-resistant isolates repo ...201728404681
dual color fluorescence in situ hybridization (fish) assays for detecting mycobacterium tuberculosis and mycobacterium avium complexes and related pathogens in cultures.two rapid dual color fluorescence in situ hybridization (fish) assays were evaluated for detecting m. tuberculosis and related pathogens in cultures. the mn genus-mtbc fish assay uses an orange fluorescent probe specific for the mycobacterium tuberculosis complex (mtbc) and a green fluorescent probe specific for the mycobacterium and nocardia genera (mn genus) to detect and distinguish mtbc from other mycobacteria and nocardia. a complementary mtbc-mac fish assay uses green and orange fluorescen ...201728399124
the new xpert mtb/rif ultra: improving detection of mycobacterium tuberculosis and resistance to rifampin in an assay suitable for point-of-care testing.the xpert mtb/rif assay (xpert) is a rapid test for tuberculosis (tb) and rifampin resistance (rif-r) suitable for point-of-care testing. however, it has decreased sensitivity in smear-negative sputum, and false identification of rif-r occasionally occurs. we developed the xpert mtb/rif ultra assay (ultra) to improve performance. ultra and xpert limits of detection (lod), dynamic ranges, and rif-r rpob mutation detection were tested on mycobacterium tuberculosis dna or sputum samples spiked with ...201728851844
molecular characterization of bovine tuberculosis strains in two slaughterhouses in morocco.bovine tuberculosis (btb) is caused by mycobacterium bovis, which belongs to the mycobacterium tuberculosis complex. mycobacterium bovis have been described to be responsible of most cases of bovine tuberculosis. although m. tuberculosis, m. africanum and non-complex mycobacteria were isolated from cattle. in morocco, so far, no molecular studies were conducted to characterize the strains responsible of btb. the present study aims to characterize m. bovis in morocco. the present study was conduc ...201728841870
the mycobacterial phosphatase ptpa regulates the expression of host genes and promotes cell proliferation.mycobacterium tuberculosis ptpa is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-jnk, p-p38, and p-vps33b, leading to suppression of host innate immunity. here we show that, in addition, ptpa enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such as gadd45a). ptpa can bind directly to the promoter region of ga ...201728811474
mycobacterium tuberculosis sige mutant st28 used as a vaccine induces protective immunity in the guinea pig model.with more than 9 million new infections and 1.5 million deaths claimed every year, tuberculosis remains one of the major scourges of humankind. the only vaccine available against this disease, the attenuated strain mycobacterium bovis, bcg is effective against severe forms of the disease in infants, but scarcely effective in protecting adults from the pulmonary form of the disease, thus not stopping transmission. consequently, the development of an effective anti-tuberculosis vaccine is a major ...201728802412
mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in spain 1998-2005.although the incidence of tuberculosis (tb) is gradually decreasing in spain, there is an increase in the proportion of foreign-born cases. this changing scenario is slowly shifting the local tb epidemiology from endemic to imported cases with an increased risk for multidrug-resistant (mdr) and extensively drug resistant (xdr) strains of mycobacterium tuberculosis complex. mdr/xdr strains from spain (n=366 mtbc isolates, 1 strain per patient) isolated between 1998 and 2005 were retained for this ...201728789982
a novel nanoemulsion vaccine induces mucosal interleukin-17 responses and confers protection upon mycobacterium tuberculosis challenge in mice.tuberculosis (tb), caused by mycobacterium tuberculosis (mtb) is contracted via aerosol infection, typically affecting the lungs. mycobacterium bovis bacillus calmette-guerin (bcg) is the only licensed vaccine and has variable efficacy in protecting against pulmonary tb. additionally, chemotherapy is associated with low compliance contributing to development of multidrug-resistant (mdr) and extensively drug-resistant (xdr) mtb. thus, there is an urgent need for the design of more effective vacci ...201728774560
design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1h)-ones.in this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1h)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against mycobacterium tuberculosis h37ra below 10 μm and against mycobacterium bovis an5a below 15 μm but were inactive against faster growing mycobacterial species. none of these selected derivatives ...201728689097
survival of mycobacterium tuberculosis and mycobacterium bovis bcg in lysosomes in vivo.mycobacterium tuberculosis is one of the most successful pathogens known, having infected more than a third of the global population. an important strategy for intracellular survival of pathogenic mycobacteria relies on their capacity to resist delivery to lysosomes, instead surviving within macrophage phagosomes. several factors of both mycobacterial and host origin have been implicated in this process. however, whether or not this strategy is employed in vivo is not clear. here we show that in ...201728689009
evaluation of the mycobacterium tuberculosis so2 vaccine using a natural tuberculosis infection model in goats.the development of new vaccines against animal tuberculosis (tb) is a priority for improving the control and eradication of this disease, particularly in those species not subjected to compulsory eradication programmes. in this study, the protection conferred by the mycobacterium tuberculosis so2 experimental vaccine was evaluated using a natural infection model in goats. twenty-six goats were distributed in three groups: (1) 10 goats served as a control group; (2) six goats were subcutaneously ...201728671074
the impact of genome region of difference 4 (rd4) on mycobacterial virulence and bcg efficacy.comparative genome analyses have revealed a number of regions of difference (rd) among mycobacterial species. the functional consequences of most of these genome variations have not been studied. rd4, which encompasses rv1506c-rv1516c of mycobacterium tuberculosis (m. tb) h37rv, is absent in the closely related mycobacterium bovis and m. bovis bacille calmette-guérin (bcg). on the other hand, we previously found that mycobacterium marinum has an extended rd4 which includes a number of genes invo ...201728642843
microrna-144-3p inhibits autophagy activation and enhances bacillus calmette-guérin infection by targeting atg4a in raw264.7 macrophage cells.micrornas (mirnas) are small noncoding nucleotides that play major roles in the response of host immune cells. autophagy plays a key role in activating the antimicrobial host defense against mycobacterium tuberculosis (m. tuberculosis). whether mirnas specifically influence the activation of macrophage autophagy during m. tuberculosis infection is largely unknown. in the present study, we demonstrate that mycobacterium bovis bacillus calmette-guérin (bcg) infection of macrophages leads to increa ...201728636635
evaluation of a new rapid kit, bd mgit tbc identification test for confirmation of mycobacterium tuberculosis complex.at present, three rapid kits are available globally for the confirmation of mycobacterium tuberculosis complex (mtbc) in cultures by mpt64 antigen (mpt64 ag) detection. these include capilia tb, sd bioline, and bd mgit tbc identification (tbcid). the third kit is yet to be validated in india. we have tested this kit and compared with sd bioline using conventional tests as gold standard. seventy-one mtbc (70 m. tuberculosis and one mycobacterium bovis) and four nontuberculous mycobacteria (ntm) w ...201728631644
original mycobacterial sin, a consequence of highly homologous antigens?the role of antigens shared between mycobacteria in in-vivo cross-reactive immune responses in host animals, have been reported to be responsible for reduced bcg vaccination efficacy as well reduced specificity of routine immunological diagnostic tests. this presents with significant disease control challenges in humans and animals. the present review highlights the results of previous studies on the effect of pre-sensitization to environmental mycobacteria on either pathogenic mycobacteria and/ ...201728619159
synthesis, biological evaluation, and molecular docking studies of novel 3-aryl-5-(alkyl-thio)-1h-1,2,4-triazoles derivatives targeting mycobacterium tuberculosis.a small library of new 3-aryl-5-(alkyl-thio)-1h-1,2,4-triazoles was synthesized and screened for the antimycobacterial potency against mycobacterium tuberculosis h37 ra strain and mycobacterium bovis bcg both in active and dormant stage. among the synthesized library, 25 compounds exhibited promising anti-tb activity in the range of ic50 0.03-5.88 μg/ml for dormant stage and 20 compounds in the range of 0.03-6.96 μg/ml for active stage. their lower toxicity (>100 μg/ml) and higher selectivity (s ...201728609019
diagnosis of mycobacteria in bovine milk: an overview.tuberculosis remains as the world's biggest threat. in 2014, human tuberculosis ranked as a major infectious disease by the first time, overcoming hiv death rates. bovine tuberculosis is a chronic disease of global distribution that affects animals and can be transmitted to humans by the consumption of raw milk, representing a serious public health concern. despite the efforts of different countries to control and eradicate bovine tuberculosis, the high negative economic impact on meat and milk ...201728591268
a new adjuvant mtom mediates mycobacterium tuberculosis subunit vaccine to enhance th1-type t cell immune responses and il-2(+) t cells.the only licensed vaccine mycobacterium bovis bacillus calmette-guérin (bcg) cannot prevent the prevalence of tuberculosis (tb), which remains a major public health problem worldwide. a more effective tb vaccine than bcg is urgently needed. subunit vaccine is a promising strategy, and suitable adjuvants will benefit the development of effective tb subunit vaccines. mto, consisting of monophosphoryl lipid a (mpla), trehalose-6,6'-dibehenate (tdb), and mf59, was developed as an adjuvant of tb vacc ...201728572807
[molecular epidemiology of human mycobacterium bovis infection in aegean region, turkey].mycobacterium bovis, which has a broader host spectrum as opposed to mycobacterium tuberculosis that generally causes disease in humans, mainly leads to chronic progressive pulmonary disease in a large number of domestic and wild mammals, particularly cattle. the term "zoonotic tuberculosis (tb)" is used to describe m.bovis infection in humans. "zoonotic tb" can not be differentiated clinically, radiologically or pathologically from tb caused by m.tuberculosis. the aim of this study was to evalu ...201728566080
prevalence of tuberculous lymphadenitis in slaughtered cattle in eastern cape, south africa.to detect the prevalence of mycobacterium tuberculosis complex (mtbc) in the lymph nodes of slaughtered cattle collected from selected abattoirs in eastern cape province of south africa.201728552545
total igm and anti-phosphatidylcholine igm antibody secretion continue after clearance of mycobacterium bovis bacillus calmette-guerin pleural infection.the cellular immune response to mycobacterium tuberculosis infection has been well characterized, while the humoral antibody response remains underexplored. we aimed to examine the total and anti-phospholipid igm levels in the pleural lavage from mice with mycobacterium bovis bcg extrapulmonary infection. we found that the levels of total and anti-phosphatidylcholine igm antibodies remained significantly higher in infected mice as compared to non-infected mice up to day 90 after bcg infection, w ...201728551717
mycobacterium tuberculosis lipoprotein mpt83 induces apoptosis of infected macrophages by activating the tlr2/p38/cox-2 signaling pathway.tuberculosis caused by mycobacterium tuberculosis continues to pose a serious global health threat. the attenuated mycobacterium bovis bacillus calmette-guérin, as the only licensed vaccine, has limited protective efficacy against tb. the development of more effective antituberculosis vaccines is urgent and demands for further identification and understanding of m. tuberculosis ags. mpt83 (rv2873), a secreted mycobacterial lipoprotein, has been applied into subunit vaccine development and shown ...201728507027
etha/r-independent killing of mycobacterium tuberculosis by ethionamide.ethionamide (eth) is part of the drug arsenal available to treat multi-drug resistant tuberculosis. the current paradigm of this pro-drug activation involves the mycobacterial enzyme etha and the transcriptional repressor, ethr. however, several lines of evidence suggest the involvement of additional players. the etha/r locus was deleted in mycobacterium bovis bcg and three mycobacterium tuberculosis (mtb) strains. while complete resistance to eth was observed with bcg etha/r ko, drug susceptibi ...201728487681
mycobacterium tuberculosis infection in a domesticated korean wild boar ( sus scrofa coreanus).tuberculosis, a chronic progressive disease, has been reported in bovine, swine, and primate species. here, we report the first case of mycobacterium tuberculosis infection in a korean wild boar ( sus scrofa coreanus). the owners this domesticated boar brought it to the gyeongbuk veterinary service laboratory in korea after it was found dead and severely emaciated. demarcated yellowish white nodules were found around the larynx and retropharyngeal lymph node during necropsy. the lungs had diffus ...201728485632
the role of hydrophobicity in tuberculosis evolution and pathogenicity.the evolution of tubercle bacilli parallels a route from environmental mycobacterium kansasii, through intermediate "mycobacterium canettii", to the modern mycobacterium tuberculosis complex. cell envelope outer membrane lipids change systematically from hydrophilic lipooligosaccharides and phenolic glycolipids to hydrophobic phthiocerol dimycocerosates, di- and pentaacyl trehaloses and sulfoglycolipids. such lipid changes point to a hydrophobic phenotype for m. tuberculosis sensu stricto. using ...201728465507
p2x7 receptor in bone marrow-derived cells aggravates tuberculosis caused by hypervirulent mycobacterium bovis.tuberculosis (tb) remains a serious public health problem despite the great scientific advances in the recent decades. we have previously shown that aggressive forms of tb caused by hypervirulent strains of mycobacterium tuberculosis and mycobacterium bovis are attenuated in mice lacking the p2x7 receptor, an ion channel activated by extracellular atp. therefore, p2x7 receptor is a potential target for therapeutic intervention. in vitro, hypervirulent mycobacteria cause macrophage death by a p2x ...201728450867
modulation of macrophage responses by cmx, a fusion protein composed of ag85c, mpt51, and hspx from mycobacterium tuberculosis.mycobacterium bovis bacillus calmette-guérin (bcg) is a vaccine used to prevent tuberculosis (tb). due to the poor protection conferred by bcg in adults, new, more effective formulations have been developed. a recombinant bcg vaccine expressing the cmx fusion protein ag85c_mpt51_hspx (rbcg-cmx) induced th1 and th17 responses and provided better protection than bcg. it has been shown that mycobacterium smegmatis expressing cmx also induces better protection than bcg and is a strong macrophage act ...201728446902
immune responses to bacillus calmette-guérin vaccination: why do they fail to protect against mycobacterium tuberculosis?mycobacterium tuberculosis (m.tb), the causative agent of tuberculosis (tb), is the current leading cause of death due to a single infectious organism. although curable, the broad emergence of multi-, extensive-, extreme-, and total-drug resistant strains of m.tb has hindered eradication efforts of this pathogen. furthermore, computational models predict a quarter of the world's population is infected with m.tb in a latent state, effectively serving as the largest reservoir for any human pathoge ...201728424703
design, synthesis and structure-activity relationship study of wollamide b; a new potential anti tb agent.wollamide b is a cationic antimycobacterial cyclohexapeptide that exhibits activity against mycobacterium bovis (m. bovis) (ic50 of 3.1 μm). aiming to define its structural activity relationship (sar), optimizing potency and pharmacokinetic properties, libraries of analogues were synthesized following a standard fmoc-based solid phase peptide synthesis approach. the antimycobacterial activities of wollamide b and all the synthesized analogues were tested against mycobacterium tuberculosis (mtb) ...201728423019
assessment of sputum smear-positive but culture-negative results among newly diagnosed pulmonary tuberculosis patients in tanzania.diagnosis of pulmonary tuberculosis (tb) in technology-limited countries is widely achieved by smear microscopy, which has limited sensitivity and specificity. the frequency and clinical implication of smear-positive but culture-negative among presumptive tb patients remains unclear. a cross-sectional substudy was conducted which aimed to identify the proportion of nontuberculous mycobacteria (ntm) infections among 94 "smear-positive culture-negative" patients diagnosed between january 2013 and ...201728744153
extended spectrum of antibiotic susceptibility for tuberculosis, djibouti.the horn of africa suffers from a high prevalence of tuberculosis which is reported to be partly driven by multi-drug resistant (mdr) mycobacterium tuberculosis strictu sensu strains. we conducted a prospective study to investigate m. tuberculosis complex species causing tuberculosis in djibouti; along with their in vitro susceptibility to standard anti-tuberculous antibiotics, in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. among the 118 mycobacteria isolates from 118 ...201728711677
dry-heat inactivation of "mycobacterium canettii"."mycobacterium canettii" is responsible for non-transmissible lymph node and pulmonary tuberculosis in persons exposed in the horn of africa. in the absence of direct human transmission, contaminated water and foodstuffs could be sources of contamination. we investigated the dry-heat inactivation of "m. canettii" alone and mixed into mock-infected foodstuffs by inoculating agar cylinders and milk with 10(4) colony-forming units of "m. canettii" cipt140010059 and two "m. canettii" clinical strain ...201728599677
mycobacterium canettii infection of adipose tissues.adipose tissues were shown to host mycobacterium tuberculosis which is persisting inside mature adipocytes. it remains unknown whether this holds true for mycobacterium canettii, a rare representative of the m. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. here, we infected primary murine white and brown pre-adipocytes and murine 3t3-l1 pre-adipocytes and mature adipocytes with m. canettii and m. tuberculosis as a positive control. both mycobacteria were able to infe ...201728567368
multiple abdominal abscesses - a not so common presentation of ntm.non-tuberculous mycobacteria/mycobacterium other than tuberculosis (mott) are ubiquitous organisms. they are acid fast bacilli often giving trouble to the physician to distinguish it from mycobacterium tuberculosis. these organisms are a menace for the treating physician as when to treat and when not to treat. they are often difficult to diagnose and may present in a variety of forms with propensity to cause number of infections of different body parts and organs. they are more common in immunoc ...201728709494
a strong and fortuitous case of dyspnea.a 48 year-old man with no past medical history was sent to our emergency department (ed); from a primary care clinic for hypertensive urgency of 200/130. the man reported an intermittent non-productive cough of approximately one year's duration and worsening dyspnea on exertion and orthopnea over the last month with lower extremity swelling. of note, he emigrated from honduras twenty years ago. blood pressure normalized with administration of lasix in the ed. physical exam revealed rales in lung ...201728414672
acid-fast bacterium detection and identification from paraffin-embedded tissues using a pcr-pyrosequencing method.acid-fast bacterium (afb) identification from formalin-fixed paraffin-embedded (ffpe) tissues is challenging and may not be readily available to the clinical laboratory. a method to detect and identify afb from ffpe tissues using pcr and pyrosequencing (pcr-seq) was developed and evaluated.201728735303
cutaneous mycobacterium haemophilum infections in immunocompromised patients in a tertiary hospital in bangkok, thailand: under-reported/under-recognized infection.mycobacterium haemophilum is one of the non-tuberculous mycobacteria (ntm) that can cause cutaneous infection. as acid-fast staining cannot distinguish ntm from mycobacterium tuberculosis, and as skin culture for m. haemophilum is not performed routinely, the diagnosis of m. haemophilum infection in thailand is rarely made.201428663805
nitazoxanide is active against mycobacterium leprae.nitazoxanide (ntz) is an anti-parasitic drug that also has activity against bacteria, including mycobacterium tuberculosis. our data using both radiorespirometry and live-dead staining in vitro demonstrate that ntz similarly has bactericidal against m. leprae. further, gavage of m. leprae-infected mice with ntz at 25mg/kg provided anti-mycobacterial activity equivalent to rifampicin (rif) at 10 mg/kg. this suggests that ntz could be considered for leprosy treatment.201728850614
microbial offense vs host defense: who controls the tb granuloma?the granuloma is the hallmark of tuberculosis and simultaneously signifies acquisition of an infection and induction of a host immune response. but who benefits more from the development of the granuloma, the host or the pathogen? is microbe or man dictating disease course and progression? mycobacterial diseases affect humans and animals alike, and the concepts presented in this review reflect host-pathogen interactions that influence not only mycobacterial granulomas in humans and animals but a ...201728749750
active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to mycobacterium marinum.the mechanisms governing neutrophil response to mycobacterium tuberculosis remain poorly understood. in this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to mycobacterium marinum, a close genetic relative of m. tuberculosis used to model tuberculosis. differential expression analysis following nuclear rna-seq of neutrophil active transcriptomes reveals a significan ...201728747644
phenotypic and genomic comparison of mycobacterium aurum and surrogate model species to mycobacterium tuberculosis: implications for drug discovery.tuberculosis (tb) is caused by mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. the considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating m. tuberculosis. these include the use of strains such as mycobacterium smegmatis and mycobacterium ma ...201728705154
a small-molecule allosteric inhibitor of mycobacterium tuberculosis tryptophan synthase.new antibiotics with novel targets are greatly needed. bacteria have numerous essential functions, but only a small fraction of such processes-primarily those involved in macromolecular synthesis-are inhibited by current drugs. targeting metabolic enzymes has been the focus of recent interest, but effective inhibitors have been difficult to identify. we describe a synthetic azetidine derivative, brd4592, that kills mycobacterium tuberculosis (mtb) through allosteric inhibition of tryptophan synt ...201728671682
β-ca-specific inhibitor dithiocarbamate fc14-584b: a novel antimycobacterial agent with potential to treat drug-resistant tuberculosis.inhibition of novel biological pathways in mycobacterium tuberculosis (mtb) creates the potential for alternative approaches for treating drug-resistant tuberculosis. in vitro studies have shown that dithiocarbamate-derived β-carbonic anhydrase (β-ca) inhibitors fc14-594 a and fc14-584b effectively inhibit the activity of mtb β-ca enzymes. we screened the dithiocarbamates for toxicity, and studied the in vivo inhibitory effect of the least toxic inhibitor on m. marinum in a zebrafish model. in o ...201728629306
ohmyungsamycins promote antimicrobial responses through autophagy activation via amp-activated protein kinase pathway.the induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against mycobacterium tuberculosis (mtb), a major pathogenic strain that causes human tuberculosis. in this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (oms) a and b in the antimicrobial responses against mtb infections by activating autophagy in murine bone marrow-derived macrophages (bmdms). oms robustly activated autophagy, which was essentiall ...201728611371
whib4 regulates the pe/ppe gene family and is essential for virulence of mycobacterium marinum.during the course of infection, pathogenic mycobacteria including mycobacterium tuberculosis (m. tb) encounter host environments of variable oxygen tension, ranging from the hypoxic center of granulomas to the most oxygenated region in the lung cavities. mycobacterial responses to changes of oxygen tension are critically related to infection outcomes, such as latency and reactivation. whib4 is an iron-sulfur containing transcription factor that is highly sensitive to oxygen exposure. in this stu ...201728592799
characterization of mycobacterium marinum infections in zebrafish wounds and sinus tracts.the impaired healing of mycobacterium tuberculosis-infected wounds is a clinical challenge, and the mechanisms involved are still not clear. the zebrafish model of mycobacterium marinum infection has provided surprising insights into the pathogenesis of tuberculosis in humans. similarly, the major principles and phases of cutaneous wound healing are conserved among adult mammals and adult zebrafish. here, we injected mycobacterium marinum into the dorsal muscles of adult zebrafish and observed t ...201728466489
immunogenicity and therapeutic effects of recombinant ag85ab fusion protein vaccines in mice infected with mycobacterium tuberculosis.the immune function of tuberculosis (tb) patients is disordered. by using immune regulators to assist chemotherapy for tb the curative effect might be improved. in this study, a vaccine containing mycobacterium tuberculosis (m. tuberculosis) recombinant ag85ab fusion protein (rag85ab) was constructed and evaluated. the mice were immunized intramuscularly three times at two-week intervals with ag85ab fusion protein combined with corynebacterium parvum adjuvant (rag85ab+cp). in comparison to contr ...201728625522
a versatile vector for mycobacterial protein production with a functional minimized acetamidase regulon.recombinant protein expression is a prerequisite for diverse investigations of proteins at the molecular level. for targets from mycobacterium tuberculosis it is favorable to use m. smegmatis as an expression host, a species from the same genus. in the respective shuttle vectors, target gene expression is controlled by the complex tetra-cistronic acetamidase regulon. as a result, the size of those vectors is large, rendering them of limited use, especially when the target proteins are expressed ...201728857325
inhibition of the devsr two-component system by overexpression of mycobacterium tuberculosis pknb in mycobacterium smegmatis.the devsr (dossr) two-component system, which is a major regulatory system involved in oxygen sensing in mycobacteria, plays an important role in hypoxic induction of many genes in mycobacteria. we demonstrated that overexpression of the kinase domain of mycobacterium tuberculosis (mtb) pknb inhibited transcriptional activity of the devr response regulator in mycobacterium smegmatis and that this inhibitory effect was exerted through phosphorylation of devr on thr180 within its dna-binding domai ...201728843272
two promoters in the esx-3 gene cluster of mycobacterium smegmatis respond inversely to different iron concentrations in vitro.the esx secretion system, also known as the type vii secretion system, is mostly found in mycobacteria and plays important roles in nutrient acquisition and host pathogenicity. one of the five esxs, esx-3, is associated with mycobactin-mediated iron acquisition. although the functions of some of the membrane-associated components of the esx systems have been described, the role of by mycosin-3 remains elusive. the esx-3 gene cluster encoding esx-3 in both mycobacterium tuberculosis and mycobacte ...201728841831
the α1β1 region is crucial for biofilm enhancement activity of mtc28 in mycobacterium smegmatis.we show here that mtc28, a secretory antigen of 28 kda from mycobacterium tuberculosis, is involved in biofilm formation. the exogenous addition of mtc28 to the culture medium as well its expression in mycobacterium smegmatis mc(2) 155 shows an enhancement in biofilm formation, which leads to drug resistance. structural analysis of mtc28 followed by mutational studies confirms the role of its α1β1 region in the biofilm enhancement activity. confocal and facs studies show that the α1β1 of mtc28 i ...201728833086
ppe27 in mycobacterium smegmatis enhances mycobacterial survival and manipulates cytokine secretion in mouse macrophages.mycobacterium tuberculosis pe/ppe family proteins play a vital role in antigenic diversity, host-pathogen interactions, and immune evasion. as secreted by esx-5 system, m. tuberculosis ppe27 is related to the growth and virulence of the bacilli. in this study, we expressed ppe27 in the nonpathogenic fast growing mycobacterium smegmatis. we found that the recombinant strain exhibits higher survival rate under several hostile conditions in vitro and longer persistence in mouse tissues. the surviva ...201728829246
the dynamic immunomodulatory effects of vitamin d3 during mycobacterium infection.mycobacterium tuberculosis ( mtb), is a highly infectious airborne bacterium. previous studies have found vitamin d3 to be a key factor in the defense against mtb infection, through its regulation of the production of immune-related cytokines, chemokines and effector molecules. mycobacterium smegmatis was used in our study as a surrogate of mtb. we hypothesized that the continuous presence of vitamin d3, as well as the level of severity of infection would differentially modulate host cell immune ...201728770668
identification of compounds that decrease numbers of mycobacteria in human macrophages in the presence of serum amyloid p.mϕs are a heterogeneous population of cells and include classically activated mϕs (m1) and alternatively activated mϕs (m2). mϕs can change from m1 to m2 and vice versa in response to environmental stimuli. serum amyloid p (sap) is a constitutive plasma protein that polarizes mϕs to an m2 phenotype, and part of this effect is mediated through fcγri receptors. in an effort to find ways to alter mϕs phenotypes, we screened for compounds that can block the sap-fcγri interaction. from a screen of 30 ...201728768708
complete auxotrophy for unsaturated fatty acids requires deletion of two sets of genes in mycobacterium smegmatis.the synthesis of unsaturated fatty acids in mycobacterium smegmatis is poorly characterized. bioinformatic analysis revealed four putative fatty acid desaturases in its genome, one of which, msmeg_1886, is highly homologous to desa3, the only palmitoyl/stearoyl desaturase present in the mycobacterium tuberculosis genome. a msmeg_1886 deletion mutant was partially auxotrophic for oleic acid and viable at 37°c and 25°c, although with a long lag phase in liquid medium. fatty acid analysis suggested ...201728762586
molecular and functional analysis of the mce4 operon in mycobacterium smegmatis.mycobacterium smegmatis contains 6 homologous mce (mammalian cell entry) operons which have been proposed to encode abc-like import systems. the mce operons encode up to 10 different proteins of unknown function that are not present in conventional abc transporters. we have analysed the consequences of individually deleting each of the genes of the mce4 operon of m. smegmatis, which mediates the transport of cholesterol. none of the mce4 mutants were able to grow in cholesterol suggesting that a ...201728752922
mycobacteria modify their cell size control under sub-optimal carbon sources.the decision to divide is the most important one that any cell must make. recent single cell studies suggest that most bacteria follow an "adder" model of cell size control, incorporating a fixed amount of cell wall material before dividing. mycobacteria, including the causative agent of tuberculosis mycobacterium tuberculosis, are known to divide asymmetrically resulting in heterogeneity in growth rate, doubling time, and other growth characteristics in daughter cells. the interplay between asy ...201728748182
mice bone marrow sca-1(+)/cd44(+)mesenchymal stem cells kill avirulent mycobacteria but not mycobacterium tuberculosis through modulation of cathelicidin expression via p38 mapk dependent pathway.mycobacterium tuberculosis (mtb) primarily infects lung macrophages. however, recent study has shown that mtb also infect and persist in dormant form inside the bone marrow mesenchymal stem cells (bm-mscs) even after successful antibiotic therapy. however, the mechanism(s) by which mtb survives in bm-mscs is still not known. like macrophages, bm-mscs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. here, we stud ...201728739828
role of long-chain acyl-coas in the regulation of mycolic acid biosynthesis in mycobacteria.one of the dominant features of the biology of mycobacterium tuberculosis, and other mycobacteria, is the mycobacterial cell envelope with its exceptional complex composition. mycolic acids are major and very specific components of the cell envelope and play a key role in its architecture and impermeability. biosynthesis of mycolic acid (ma) precursors requires two types of fatty acid synthases, fas i and fas ii, which should work in concert in order to keep lipid homeostasis tightly regulated. ...201728724694
modulation of trehalose dimycolate and immune system by rv0774c protein enhanced the intracellular survival of mycobacterium smegmatis in human macrophages cell line.mycobacterium tuberculosis rv0774c protein was reported previously to express under stress conditions. therefore, rv0774c gene was cloned and expressed in mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. the bacterial colonies expressing rv0774c (ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (ms_ve). enhanced survival of ms_rv0774c after treatment with streptomycin was observ ...201728713776
the putative polyketide cyclase msmeg_0129 from mycobacterium smegmatis: purification, crystallization and x-ray crystallographic analysis.mycobacterium tuberculosis rv0164 has previously been identified as a human t-cell antigen that induces significant production of ifn-γ in human peripheral blood mononuclear cells. m. smegmatis msmeg_0129 shares 59% sequence identity with rv0164. based on sequence alignment, both proteins are predicted to be members of the cyclase/dehydrase family, which is part of a large group of enzymes referred to as type ii polyketide synthases (pkss). in biosynthetic pathways mediated by type ii pkss, cycl ...201728695854
selection of a new mycobacterium tuberculosis h37rv aptamer and its application in the construction of a swcnt/aptamer/au-ide mspqc h37rv sensor.a rapid and accurate detection method for mycobacterium tuberculosis (m. tuberculosis) is essential for effectively treating tuberculosis. however, current detection methods cannot meet these clinical requirements because the methods are slow or of low specificity. consequently, a new highly specific ssdna aptamer against m. tuberculosis reference strain h37rv was selected by using the whole-cell systematic evolution of ligands by exponential enrichment technique. the selected aptamer was used t ...201728689112
the complete structure of the mycobacterium smegmatis 70s ribosome.the ribosome carries out the synthesis of proteins in every living cell. it consequently represents a frontline target in anti-microbial therapy. tuberculosis ranks among the leading causes of death worldwide, due in large part to the combination of difficult-to-treat latency and antibiotic resistance. here, we present the 3.3-å cryo-em structure of the 70s ribosome of mycobacterium smegmatis, a close relative to the human pathogen mycobacterium tuberculosis. the structure reveals two additional ...201728683309
mycobacterium tuberculosis hypoxic response protein 1 (hrp1) augments the pro-inflammatory response and enhances the survival of mycobacterium smegmatis in murine macrophages.the dosr/doss two-component regulatory system of mycobacterium tuberculosis regulates the expression of numerous genes under stress conditions and is important for the long-term survival of m. tuberculosis in the host. the rv2626c gene of m. tuberculosis is one of the most strongly induced transcripts of the dormancy regulon. this study focused on the immunological effects and possible function of rv2626c in maintaining mycobacterial survival under various stress conditions.201728671529
anti-tuberculosis bacteriophage d29 delivery with a vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler.to compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) d29 with three inhalation devices.201728646325
inhibition of biofilm formation in mycobacterium smegmatis by parinari curatellifolia leaf extracts.tuberculosis (tb) is a serious public health problem worldwide. mycobacterium tuberculosis (m. tuberculosis) grows as drug tolerant pellicles. agents that inhibit biofilm formation in m. tuberculosis have the potential to reduce the disease treatment period and improve the quality of tuberculosis chemotherapy. parinari curatellifolia (p. curatellifolia) leaf extracts are claimed to treat symptoms similar to tuberculosis in ethnomedicinal practices. mycobacterium smegmatis (m. smegmatis) is a sur ...201728558683
new isoflavonoids from the extract of rhynchosia precatoria (humb. & bonpl. ex willd.) dc. and their antimycobacterial activity.the evaluation of the antimycobacterial activity of extracts of medicinal plants used by mayos against tuberculosis and respiratory problems, allowed the identification of rhynchosia precatoria (humb. & bonpl. ex willd.) dc (fabaceae) as the best candidate to find new antimycobacterial compounds.201728506901
chemical activation of adenylyl cyclase rv1625c inhibits growth of mycobacterium tuberculosis on cholesterol and modulates intramacrophage signaling.mycobacterium tuberculosis (mtb) uses a complex 3', 5'-cyclic amp (camp) signaling network to sense and respond to changing environments encountered during infection, so perturbation of camp signaling might be leveraged to disrupt mtb pathogenesis. however, understanding of camp signaling pathways is hindered by the presence of at least 15 distinct adenylyl cyclases (acs). recently, the small molecule v-58 was shown to inhibit mtb replication within macrophages and stimulate camp production in m ...201728464471
unravelling the pleiotropic role of the mceg atpase in mycobacterium smegmatis.the mce systems are complex abc transporters that are encoded by different numbers of homologous operons in actinobacteria. while the four mce systems of mycobacterium tuberculosis are all energized by a single atpase, mceg, each system appears to import different fatty acids or sterols. to explore if this behaviour can be extended to saprophytic mycobacteria, whose more complex genomes encode more mce systems, we have identified and characterized the mceg orthologue of mycobacterium smegmatis. ...201728447386
anti-mycobacterium activity of microbial peptides in a silkworm infection model with mycobacterium smegmatis.an in vivo-mimic silkworm infection model with mycobacterium smegmatis was established. when silkworms were raised at 37 °c following an injection of m. smegmatis cells (1.25 × 10(7) cfu larva(-1) g(-1)) into the silkworm hemolymph, they died within 48 h. under these conditions, four microbial peptides with anti-m. smegmatis activity, lariatin a, calpinactam, lysocin e and propeptin, exerted therapeutic effects in a dose-dependent manner, and these are also clinically used agents that are active ...201728446822
mycobacterium tuberculosis pe_pgrs41 enhances the intracellular survival of m. smegmatis within macrophages via blocking innate immunity and inhibition of host defense.the success of mycobacterium tuberculosis (m. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. the genome of m. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic pe_ppe family. despite of intense research, the roles of pe_pgrs proteins in mycobacterial pathogenesis remain elusive. the function of m. tuberculosis pe_pgrs41, characterized by an extended and unique c-terminal domain, was s ...201728440335
identification of mycobacterial genes involved in antibiotic sensitivity: implications for the treatment of tuberculosis with β-lactam-containing regimens.in a mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaa, dpre2, rpst, and para displayed hypersusceptibility to antibiotics, including the β-lactams meropenem, ampicillin, amoxicillin, and cefotaxime. sub-mic levels of octoclothepin, a psychotic drug inhibiting para, phenocopied the para insertion and enhanced the bactericidal activity of meropenem against mycobacterium tuberculosis in combination with clavulanate. our study identifies novel factors associa ...201728438925
involvement of methylated hbha expressed from mycobacterium smegmatis in an ifn-γ release assay to aid discrimination between latent infection and active tuberculosis in bcg-vaccinated populations.ifn-γ release assays (igras) based on region of difference 1 (rd1) antigens have improved diagnosis of mycobacterium tuberculosis (m. tb) infection. however, igras with these antigens cannot discriminate between active tuberculosis (atb) and latent tuberculosis infection (ltbi). m. tb heparin-binding-hemagglutinin (hbha) induces relatively high ifn-γ responses in ltbi individuals and low responses in atb patients, but purification of the native methylated hbha from cultures of m. tb for immunolo ...201728429162
mutation at g103 of mtbftsz altered their sensitivity to coumarins.coumarins are natural polyphenol lactones comprising of fused rings of benzene and α-pyrone. the current study demonstrates the inhibitory effect of coumarins with various substitutions on mycobacterium smegmatis mc(2) 155. we also demonstrate the effect of pomegranate (punica granatum) extract containing ellagic acid, on m. smegmatis as well as their affect on mtbftsz (ftsz from mycobacterium tuberculosis). the ellagic acid extracts from pomegranate peels inhibit mycobacteria with a mic of 25 μ ...201728428773
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