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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
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
plants in our combating strategies against mycobacterium tuberculosis: progress made and obstacles met.traditionally used plants for treating chest-related problems/tuberculosis (tb) have not been evaluated in detail and hence a thorough study is needed in this regard. this knowledge may find application in developing new anti-tb drugs.201728385088
tuberculosis among foreign-born persons diagnosed ≥10 years after arrival in the united states, 2010-2015.the majority of tuberculosis (tb) cases in the united states are attributable to reactivation of latent tb infection (ltbi) (1). ltbi refers to the condition when a person is infected with mycobacterium tuberculosis without signs and symptoms, or radiographic or bacteriologic evidence of tb disease. cdc and the u.s. preventive services task force (uspstf) recommend screening populations at increased risk for ltbi, including persons who have lived in congregate settings at high risk and persons w ...201728333913
evaluation of pulmonary tuberculosis case detection improvement with the deployment of xpertmtb/rif in the tuberculosis control program of cross river state, nigeria.global indices show that nigeria has the highest tuberculosis (tb)-related mortality rate. overdependence on ziehl-neelsen (zn) smear microscopy for diagnosis and human immunodeficiency virus (hiv)/aids has limited control efforts. the new polymerase chain reaction-based xpertmtb/rif (cepheid inc., ca, usa), which detects mycobacterium tuberculosis and rifampicin resistance, was introduced in cross river state in 2014. we evaluated the increment in pulmonary tb case detection following introduct ...201728317812
tb-iris: proteomic analysis of in vitro pbmc responses to mycobacterium tuberculosis and response modulation by dexamethasone.paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (tb-iris) occurs in 8-54% of south african patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. improved tb-iris molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. we assessed how tb-iris status and dexamethasone influence leukocyte proteomic responses to mycobacterium tuberculosis (mtb). patient blood was obtained th ...201728209523
effector mechanisms of neutrophils within the innate immune system in response to mycobacterium tuberculosis infection.neutrophils have a significant yet controversial role in the innate immune response to mycobacterium tuberculosis (m. tb) infection, which is not yet fully understood. in addition to neutrophils' well-known effector mechanisms, they may also help control infection of m. tb through the formation of neutrophil extracellular traps (nets), which are thought to further promote the killing of m. tb by resident alveolar macrophages. cytokines such as ifn-γ have now been shown to serve an immunomodulato ...201728178208
risk factors for readmission to hospital in patients with tuberculosis in tehran, iran: three-year surveillance.tuberculosis (tb) is still a major health problem and tb hospital readmission could increase health system costs. in a retrospective study in a tertiary referral hospital for tb in tehran, iran, tb patients with readmission were evaluated. these tb patients in the index year who were then readmitted were compared with tb patients in the same year who were not readmitted during the follow-up period. one hundred and forty-six patients had hospital readmission within three-year follow-up with mean ...201728166697
hepatic tuberculosis in human immunodeficiency virus co-infected adults: a case series of south african adults.although mycobacterium tuberculosis (tb) infection may cause extrapulmonary disease in hiv-infected adults, hiv-associated hepatic tb has been poorly characterized. our objective was to describe hepatic tb in hiv-infected adults.201728148232
the role of uv radiation and vitamin d in the seasonality and outcomes of infectious disease.the seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. one of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (uvr), and its subsequent control of vitamin d production. here we show how uvr and vitamin d, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne ...201728078341
transmission of extensively drug-resistant tuberculosis in south africa.background drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (hiv) infection worldwide. a widespread epidemic of extensively drug-resistant (xdr) tuberculosis is occurring in south africa, where cases have increased substantially since 2002. the factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. methods we conducted a prospective study involving 4 ...201728099825
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
resistance to thiacetazone derivatives active against mycobacterium abscessus involves mutations in the mmpl5 transcriptional repressor mab_4384.available chemotherapeutic options are very limited against mycobacterium abscessus, which imparts a particular challenge in the treatment of cystic fibrosis (cf) patients infected with this rapidly growing mycobacterium. new drugs are urgently needed against this emerging pathogen, but the discovery of active chemotypes has not been performed intensively. interestingly, however, the repurposing of thiacetazone (tac), a drug once used to treat tuberculosis, has increased following the decipherin ...201728096157
integration of biomass formulations of genome-scale metabolic models with experimental data reveals universally essential cofactors in prokaryotes.the composition of a cell in terms of macromolecular building blocks and other organic molecules underlies the metabolic needs and capabilities of a species. although some core biomass components such as nucleic acids and proteins are evident for most species, the essentiality of the pool of other organic molecules, especially cofactors and prosthetic groups, is yet unclear. here we integrate biomass compositions from 71 manually curated genome-scale models, 33 large-scale gene essentiality data ...201727939572
engineering bacteria to manufacture functionalized polyester beads.the ability to generate tailor-made, functionalized polyester (polyhydroxyalkanoate, pha) beads in bacteria by harnessing their natural carbon-storage granule production system is an exciting recent development. proteins that naturally attach to the polyester granule core were rationally engineered to enable in vivo production of pha beads which are applicable in bioseparation, protein purification, enzyme immobilization and diagnostics and which show advantageous properties toward the developme ...201722705844
an interactive macrophage signal transduction map facilitates comparative analyses of high-throughput data.macrophages (mϕs) are key players in the coordination of the lifesaving or detrimental immune response against infections. the mechanistic understanding of the functional modulation of mϕs by pathogens and pharmaceutical interventions at the signal transduction level is still far from complete. the complexity of pathways and their cross-talk benefits from holistic computational approaches. in the present study, we reconstructed a comprehensive, validated, and annotated map of signal transduction ...201728137890
crystal structure and biochemical investigations reveal novel mode of substrate selectivity and illuminate substrate inhibition and allostericity in a subfamily of xaa-pro dipeptidases.xaa-pro dipeptidase (xpd) catalyzes hydrolysis of iminopeptide bond in dipeptides containing trans-proline as a second residue. xpds are found in all living organisms and are believed to play an essential role in proline metabolism. here, we report crystal structures and extensive enzymatic studies of xpd from xanthomonas campestris (xpdxc), the first such comprehensive study of a bacterial xpd. we also report enzymatic activities of its ortholog from mycobacterium tuberculosis (xpdmt). these en ...201727816563
species dependent impact of helminth-derived antigens on human macrophages infected with mycobacterium tuberculosis: direct effect on the innate anti-mycobacterial response.in countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. while mycobacterium tuberculosis (mtb) gives rise to a pro-inflammatory th1 response, a th2 response is typical of helminth infections. a strong th2 response has been associated with decreased protection against tuberculosis.201728192437
immunogenic properties of lactobacillus plantarum producing surface-displayed mycobacterium tuberculosis antigens.tuberculosis (tb) remains among the most deadly diseases in the world. the only available vaccine against tuberculosis is the bacille calmette-guérin (bcg) vaccine, which does not ensure full protection in adults. there is a global urgency for the development of an effective vaccine for preventing disease transmission, and it requires novel approaches. we are exploring the use of lactic acid bacteria (lab) as a vector for antigen delivery to mucosal sites. here, we demonstrate the successful exp ...201727815271
hiv status among patients with tuberculosis and hiv testing practices by connecticut health care providers.knowing the human immunodeficiency virus (hiv) status of persons infected with mycobacterium tuberculosis is important for individual treatment and preventing transmission. this evaluation analyzed surveillance data and surveyed health care providers who care for patients with hiv and tuberculosis (tb) to understand the factors contributing to suboptimal levels of connecticut patients with tb having a known hiv status. during 2008 to 2010, 208 (76.2%) of 273 patients had a known hiv status; 12 ( ...201723442493
ga(iii) nanoparticles inhibit growth of both mycobacterium tuberculosis and hiv and release of interleukin-6 (il-6) and il-8 in coinfected macrophages.treatment of individuals coinfected with human immunodeficiency virus (hiv) type 1 and mycobacterium tuberculosis is challenging due to the prolonged treatment requirements, drug toxicity, and emergence of drug resistance. mononuclear phagocytes (mp; macrophages) are one of the natural reservoirs for both hiv and m. tuberculosis here, the treatment of hiv and m. tuberculosis coinfection was studied by preloading human macrophages with mp-targeted gallium (ga) nanoparticles to limit subsequent si ...201728167548
tuberculosis 'the great imitator': a usual disease with unusual presentations.a number of infectious diseases have been referred to by the phrase 'the great imitator', of which the oldest is syphilis; others include lyme disease, nocardiosis, etc. tuberculosis has been described as the second great imitator as it can imitate various other disease processes. an awareness of the atypical clinical manifestations of tuberculosis is important, especially in regions where tuberculosis continues to be a major public health problem, such as india. extrapulmonary tuberculosis (ept ...201728166920
thoracic diseases associated with hiv infection in the era of antiretroviral therapy: clinical and imaging findings.the human immunodeficiency virus (hiv) and acquired immunodeficiency syndrome (aids) pandemic has entered its 4th decade. since the introduction of combination antiretroviral therapy (art) in 1996, the number of aids-related deaths has plateaued worldwide. today, owing to the effectiveness of art, the hiv-infected population is aging and hiv infection has become a chronic illness. non-aids comorbidities are increasing, and the spectrum of hiv-related thoracic diseases is evolving. in developed c ...201725019430
potential of zanthoxylum leprieurii as a source of active compounds against drug resistant mycobacterium tuberculosis.tuberculosis (tb) is still a global health problem mainly due to development of resistance and co-infection with the human immune virus (hiv). treatment of multi and extensively drug resistant tb requires use of second line drugs which are less efficacious, expensive and very toxic. this has necessitated a need to search for new treatment regimens especially from medicinal plants. zanthoxylum leprieurii, a plant species from rutaceae is used locally in the treatment of tuberculosis in uganda. th ...201728148252
baseline hbv load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis.hepatitis associated anti-tuberculous treatment (hatt) has been a main obstacle in managing patients co-infected with mycobacterium tuberculosis and hepatitis b virus (hbv). therefore, we evaluated the factors related to the severity of adverse effects during hatt, especially those associated with liver failure. a retrospective study was carried out at tongji hospital from 2007 to 2012. increases in serum transaminase levels of >3, 5, and 10 times the upper limit of normal (uln) were used to def ...201728224437
crispr/cas9-the ultimate weapon to battle infectious diseases?infectious diseases are a leading cause of death worldwide. novel therapeutics are urgently required to treat multidrug-resistant organisms such as mycobacterium tuberculosis and to mitigate morbidity and mortality caused by acute infections such as malaria and dengue fever virus as well as chronic infections such as human immunodeficiency virus-1 and hepatitis b virus. the clustered regularly interspaced short palindromic repeats (crispr)/crispr-associated protein 9 (cas9) system, which has rev ...201727860197
mait cells are reduced in frequency and functionally impaired in human t lymphotropic virus type 1 infection: potential clinical implications.htlv-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition htlv-1-associated myelopathy/tropical spastic paraparesis (ham/tsp). it is unclear why a minority of infected subjects develop ham/tsp. the cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. furthermore, htlv-1-infected individuals have an increase inciden ...201728384290
mycobacterium tuberculosis infection among persons who inject drugs in san diego, california.persons who inject drugs (pwid) might be at increased risk for mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (ltbi) due to their injection drug use.201728284258
miliary tuberculosis infection during hepatitis c treatment with sofosbuvir and ledipasvir plus ribavirin.chronic hepatitis c virus (hcv) infection is one of the main causes of chronic liver disease worldwide. in the last 5 years, treatment for hcv infection has experienced a marked development. in 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. however, new side effects have been associated. we report the first case of an hcv infected patient treated for 12 wk with the comb ...201728217253
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
epidemiology of infectious encephalitis causes in 2016.we performed a literature search in the medline database, using the pubmed website. the incidence of presumably infectious encephalitis is estimated at 1.5-7 cases/100,000 inhabitants/year, excluding epidemics. infectious encephalitis and immune-mediated encephalitis share similar clinical signs and symptoms. the latter accounts for a significant proportion of presumably infectious encephalitis cases without any established etiological diagnosis; as shown from a prospective cohort study where 21 ...201728341533
management of adult infectious encephalitis in metropolitan france.infectious encephalitis is a severe disease leading to a high mortality and morbidity. the most frequent causes include herpes simplex virus, varicella zoster virus, listeria monocytogenes, and mycobacterium tuberculosis. urgent treatment is required (anti-infective therapy and nonspecific supportive care). the aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review.201728336304
influence of socio-economic inequality measured by the gini coefficient on meningitis incidence caused by mycobacterium tuberculosis and haemophilus influenzae in colombia, 2008-2011.bacterial meningitis is an important cause of infectious neurological morbidity and mortality. its incidence has decreased with the introduction of vaccination programmes against preventable agents. however, low-income and middle-income countries with poor access to health care still have a significant burden of the disease. thus, the relationship between the gini coefficient and h. influenzae and m. tuberculosis meningitis incidence in colombia, during 2008-2011, was assessed. in this ecologica ...201728353449
discovery of anti-microbial and anti-tubercular molecules from fusarium solani: an endophyte of glycyrrhiza glabra.glycyrrhiza glabra is a high-value medicinal plant thriving in biodiversity rich kashmir himalaya. the present study was designed to explore the fungal endophytes from g. glabra as a source of bioactive molecules.201728150900
efficacy of resistance to francisella imparted by ity/nramp/slc11a1 depends on route of infection.natural resistance-associated macrophage protein (nramp) encoded by the slc11a1 gene is a membrane-associated transporter of divalent metal ions. murine slc11a1 has two known alleles, a functional slc11a1(gly169), which is found in dba2/j, nod/ltj, and 129p3/j and related mouse strains, and a non-functional slc11a1(asp169), that is found in c56bl/6j (b6) and balb/cj mice. b6 mice congenic for slc11a1(gly169) (b6-slc11a1(g169) ) are markedly resistant to the intracellular pathogens salmonella, le ...201728360906
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
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
[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
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
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
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
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
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
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
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
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
radiopathological features and identification of mycobacterial infections in granulomatous nodules resected from the lung.pulmonary granulomas are sometimes resected because they resemble lung cancer and false-positive findings come through from positron emission tomography (pet) using 18fluorine-fluorodeoxyglucose (18f-fdg). mycobacterial infection is a common cause of granulomas.201728219077
non-tuberculous mycobacteria in south african wildlife: neglected pathogens and potential impediments for bovine tuberculosis diagnosis.non-tuberculous mycobacteria (ntm) are not only emerging and opportunistic pathogens of both humans and animals, but from a veterinary point of view some species induce cross-reactive immune responses that hamper the diagnosis of bovine tuberculosis (btb) in both livestock and wildlife. little information is available about ntm species circulating in wildlife species of south africa. in this study, we determined the diversity of ntm isolated from wildlife species from south africa as well as bot ...201728194371
pathogen identification in suspected cases of pyogenic spondylodiscitis.pyogenic spinal infection continues to represent a worldwide problem. in approximately one-third of patients with pyogenic spondylodiscitis, the infectious agent is never identified. of the cases that lead to organismal identification, bacteria are more commonly isolated from the spine rather than fungi and parasites. this study applied universal prokaryotic 16s rrna pcr as a rapid diagnostic tool for the detection of bacterial agents in specimens from patients suspected of pyogenic spondylodisc ...201728337426
drug susceptibility of rapid and slow growing non-tuberculous mycobacteria isolated from symptomatics for pulmonary tuberculosis, central india.non-tuberculous mycobacteria (ntm) are emerging as important pathogens. their treatment also differs from that of mycobacterium tuberculosis. in india, any datum on them is scarce as species identification and drug susceptibility are not performed in most laboratories. susceptibility also differs from one geographic area to another, and in our country, there are no data even to guide the clinicians to start treatment empirically.201727934821
in vitro susceptibility testing of tedizolid against nontuberculous mycobacteria.tedizolid is a new oxazolidinone with improved in vitro and intracellular potency against mycobacterium tuberculosis, including multidrug resistant strains, and some species of nontuberculous mycobacteria (ntm) compared with linezolid.using the current clinical and laboratory standards institute (clsi) recommended method of broth microdilution, susceptibility testing of 170 isolates of rapidly growing mycobacteria showed equivalent or lower (1- to 8-fold mic50 and/or mic90 values) for tedizolid ...201728330892
nontuberculous mycobacterial infection in rheumatoid arthritis patients: a single-center experience in south korea.nontuberculous mycobacteria (ntm) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (ra) patients. this study aimed to identify the incidence and clinical characteristics of ntm infection in ra patients living in tuberculosis (tb) infection endemic area.201728063416
learning from epidemiological, clinical, and immunological studies on mycobacterium africanum for improving current understanding of host-pathogen interactions, and for the development and evaluation of diagnostics, host-directed therapies, and vaccines for tuberculosis.mycobacterium africanum comprises two phylogenetic lineages within the mycobacterium tuberculosis complex (mtbc). m. africanum was first described and isolated in 1968 from the sputum of a senegalese patient with pulmonary tuberculosis (tb) and it has been identified increasingly as an important cause of human tb, particularly prevalent in west africa. the restricted geographical distribution of m. africanum, in contrast to the widespread global distribution of other species of mtbc, requires ex ...201727979782
non-tuberculous mycobacteria: classification, diagnostics, and therapy.non-tuberculous mycobacteria (ntm) are species other than those belonging to the mycobacterium tuberculosis complex and do not cause leprosy. ntm are generally free-living organisms that are ubiquitous in the environment. there have been more than 140 ntm species identified to-date. they can cause a wide range of infections, with pulmonary infections being the most frequent (65-90 %). there is growing evidence that the incidence of ntm lung diseases and associated hospitalizations are on the ris ...201727826888
mixed infection of mycobacterium abscessus subsp. abscessus and mycobacterium tuberculosis in the lung.a mixed infection of mycobacterium abscessus subsp. abscessus (mab) and mycobacterium tuberculosis (mtb) in the lung is an unusual clinical manifestation and has not yet been reported. a 61-year-old woman had been treated for mab lung disease and concomitant pneumonia, and was diagnosed with pulmonary tuberculosis (ptb). despite both anti-ptb and anti-mab therapy, her entire left lung was destroyed and collapsed. she underwent left pneumonectomy and received medical therapy. we were able to succ ...201728180105
case report on pulmonary disease due to coinfection of mycobacterium tuberculosis and mycobacterium abscessus: difficulty in diagnosis.mycobacterium abscessus, which is ubiquitous environmental organism, is more likely to cause pulmonary infection in the presence underlying lung disease and immunosuppression. we report a case of pulmonary disease due to coinfection of mycobacterium tuberculosis (mtb) and mycobacterium abscessus (m. abscessus) in an immunocompetent patient without underlying lung disease. healthcare professionals should be aware of co-infection with mtb and m. abscessus, and treatment should be based on clinical ...201728180066
emergence of mmpt5 variants during bedaquiline treatment of mycobacterium intracellulare lung disease.bedaquiline (bdq), a diarylquinoline antibiotic that targets atp synthase, is effective for the treatment of mycobacterium tuberculosis infections that no longer respond to conventional drugs. while investigating the off-label use of bdq as salvage therapy, seven of 13 patients with mycobacterium intracellulare lung disease had an initial microbiological response and then relapsed. whole-genome comparison of pretreatment and relapse isolates of m. intracellulare uncovered mutations in a previous ...201727927925
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
inhibition of β-lactamases of mycobacteria by avibactam and clavulanate.mycobacterium tuberculosis and mycobacterium abscessus produce broad-spectrum class a β-lactamases, blac and bla mab , which are inhibited by clavulanate and avibactam, respectively. blac differs from bla mab at ambler position 132 in the conserved motif sdn (sdg versus sdn, respectively). here, we investigated whether this polymorphism could account for the inhibition specificity of β-lactamases from slowly and rapidly growing mycobacteria.201728039278
novel chemical scaffolds for inhibition of rifamycin-resistant rna polymerase discovered from high-throughput screening.rifampin has been a cornerstone of tuberculosis (tb) treatment since its introduction. the rise of multidrug-resistant and extensively drug-resistant tb makes the development of novel therapeutics effective against these strains an urgent need. site-specific mutations in the target enzyme of rifampin, rna polymerase (rnap) comprises the majority (~97%) of rifamycin-resistant (rif(r)) strains of mycobacterium tuberculosis (mtb). to identify novel inhibitors of bacterial rnap, an in vitro plasmid- ...201728027449
structural basis for rifamycin resistance of bacterial rna polymerase by the three most clinically important rpob mutations found in mycobacterium tuberculosis.since 1967, rifampin (rmp, a rifamycin) has been used as a first line antibiotic treatment for tuberculosis (tb), and it remains the cornerstone of current short-term tb treatment. increased occurrence of rifamycin-resistant (rif(r) ) tb, ∼41% of which results from the rpob s531l mutation in rna polymerase (rnap), has become a growing problem worldwide. in this study, we determined the x-ray crystal structures of the escherichia coli rnaps containing the most clinically important s531l mutation ...201728009073
intrinsic rifamycin resistance of mycobacterium abscessus is mediated by adp-ribosyltransferase mab_0591.rifampicin, a potent first-line tb drug of the rifamycin group, shows only little activity against the emerging pathogen mycobacterium abscessus. reportedly, bacterial resistance to rifampicin is associated with polymorphisms in the target gene rpob or the presence of enzymes that modify and thereby inactivate rifampicin. the aim of this study was to investigate the role of the mab_0591 (arrmab)-encoded rifampicin adp-ribosyltransferase (arr_mab) in innate high-level rifampicin resistance in m. ...201727999011
high-throughput identification of dna-encoded igg ligands that distinguish active and latent mycobacterium tuberculosis infections.the circulating antibody repertoire encodes a patient's health status and pathogen exposure history, but identifying antibodies with diagnostic potential usually requires knowledge of the antigen(s). we previously circumvented this problem by screening libraries of bead-displayed small molecules against case and control serum samples to discover "epitope surrogates" (ligands of iggs enriched in the case sample). here, we describe an improved version of this technology that employs dna-encoded li ...201727957856
native esi mass spectrometry can help to avoid wrong interpretations from isothermal titration calorimetry in difficult situations.we studied by native esi-ms the binding of various dna-polymerase-derived peptides onto dna-polymerase processivity rings from escherichia coli, pseudomonas aeruginosa, and mycobacterium tuberculosis. these homodimeric rings present two equivalent specific binding sites, which leads to successive formation during a titration experiment of singly- and doubly occupied rings. by using the esi-ms free-ring spectrum as a ruler, we derived by robust linear regression the fractions of the different rin ...201727957716
evolutionary adaptation of the essential trna methyltransferase trmd to the signaling molecule 3',5'-camp in bacteria.the nucleotide signaling molecule 3',5'-cyclic adenosine monophosphate (3',5'-camp) plays important physiological roles, ranging from carbon catabolite repression in bacteria to mediating the action of hormones in higher eukaryotes, including human. however, it remains unclear whether 3',5'-camp is universally present in the firmicutes group of bacteria. we hypothesized that searching for proteins that bind 3',5'-camp might provide new insight into this question. accordingly, we performed a geno ...201727881678
mycobacterium tuberculosis rv0560c is not essential for growth in vitro or in macrophages.mycobacterium tuberculosis rv0560c, a putative benzoquinone methyl transferase, is heavily induced in response to salicylate exposure. it has some similarity to escherichia coli ubig, although its role in ubiquinone or menaquinone synthesis is not clear, since m. tuberculosis is not known to produce ubiquinone. we constructed an unmarked in-frame deletion of rv0560c in m. tuberculosis to determine its role in vitro. deletion of rv0560c in m. tuberculosis had no effect on growth in medium contain ...201728061949
structure and interactions of reca: plasticity revealed by molecular dynamics simulations.eleven independent simulations, each involving three consecutive molecules in the reca filament, carried out on the protein from mycobacterium tuberculosis, mycobacterium smegmatis and escherichia coli and their adenosine triphosphate (atp) complexes, provide valuable information which is complementary to that obtained from crystal structures, in addition to confirming the robust common structural framework within which reca molecules from different eubacteria function. functionally important lo ...201728049371
a novel self-cleavable tag zbasic-∆i-cm and its application in the soluble expression of recombinant human interleukin-15 in escherichia coli.soluble expression of recombinant therapeutic proteins in escherichia coli (e. coli) has been a challenging task in biopharmaceutical development. in this study, a novel self-cleavable tag zbasic-intein has been constructed for the soluble expression and purification of a recombinant cytokine, human interleukin-15 (il-15). we screened several solubilizing tags fused with the self-cleavable mycobacterium tuberculosis reca mini-intein ∆i-cm and demonstrated that zbasic tag can significantly improv ...201727683210
consensus numbering system for the rifampicin resistance-associated rpob gene mutations in pathogenic mycobacteria.the rpob gene codes for the rna polymerase β subunit, which is the target of rifampicin, an essential drug in the treatment of tuberculosis and other mycobacterial infections. this gene is present in all bacteria, but its length and nucleotide sequence vary between bacterial species, including mycobacteria. mutations in the rpob gene alter the structure of this protein and cause drug resistance. to describe the resistance-associated mutations, the scientific and medical communities have been usi ...201727664776
fusion molecules of heat shock protein hspx with other antigens of mycobacterium tuberculosis show high potential in serodiagnosis of tuberculosis.variable individual response against the antigens of mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. antigens of m. tuberculosis hspx and pe35 were expressed in a soluble form whereas tnpsts1 and fbpc1 were expressed as inclusion bodies at 37°c. heat shock protein hspx when attached to the n ...201727654048
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
strong anti-epstein barr virus (ebv) or cytomegalovirus (cmv) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy.intact immune responses to cytomegalovirus (cmv) and epstein-barr virus (ebv) represent a biologically and clinically relevant correlate of 'immunological fitness' in humans. however, there is a lack of knowledge concerning anti-ebv or anti-cmv responses in patients with pulmonary tuberculosis (tb), in whom aberrant immune responses may promote progression of clinical disease.201728193504
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
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