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role for gr-1+ cells in the control of high-dose mycobacterium bovis recombinant bcg.mycobacterium bovis bacillus calmette-guérin (bcg) is an attractive target for development as a live vaccine vector delivering transgenic antigens from hiv and other pathogens. most studies aimed at defining the clearance of bcg have been performed at doses between 10(2) and 10(4) cfu. interestingly, however, recombinant bcg (rbcg) administered at doses of >10(6) cfu effectively generates antigen-specific t-cell responses and primes for heterologous boost responses. thus, defining clearance at h ...201424920602
some nigerian anti-tuberculosis ethnomedicines: a preliminary efficacy assessment.nigerian herbalists possess indigenous ethnomedicinal recipes for the management of tuberculosis and related ailments. a collaborative preliminary modern scientific evaluation of the efficacy of some nigerian ethnomedicines used by traditional medicine practitioners (tmps) in the management of tuberculosis and related ailments has been carried out.201424911338
vaccination of domestic animals against tuberculosis: review of progress and contributions to the field of the tbstep project.tuberculosis either caused by mycobacterium bovis or m. caprae is a significant burden to agricultural industries worldwide. vaccination of domestic ruminant species such as cattle and goats constitutes a potential tool to support disease control. this review will discuss recent progress made to develop tuberculosis vaccines against domestic ruminants as well as approaches to differentiate vaccinated and infected animals (diva) and biomarker discovery studies.201424908189
disseminated mycobacterium bovis infection in red foxes (vulpes vulpes) with cerebral involvement found in portugal.a total of 49 road-killed red foxes were used for the detection of mycobacterium tuberculosis complex (mtc) in portugal. mtc infection was detected by pcr in 10 red foxes (20.4%; 95% confidence interval [ci] 8.8-31.2%) and confirmed in three (6.1%; 95% ci 0.0-7.9%) of them by microbiological culture. the complex was detected in 20 tissues out of 441 by pcr techniques (4.5%; 95% ci 16.3-23.7%) and in seven tissues out of 441 (1.6%; 95% ci 4.6-9.4%) by culture. mtc was most frequently detected in ...201424901256
optimization of modified middlebrook 7h11 agar for isolation of mycobacterium bovis from raw milk cheese.reports have highlighted the absence of contemporary peer reviewed publications pertaining to mycobacterium bovis culture from raw milk and cheese. by replicating traditional methods, cheese-making methodology and equipment were devised to produce cheddar (n = 6) and caerphilly (n = 3) artificially contaminated with m. bovis (three genotypes) under stringent laboratory-containment guidelines for handling hazardous microbiological material. middlebrook 7h11, modified for m. bovis isolation, was a ...201424888395
innate cytokine profiling of bovine alveolar macrophages reveals commonalities and divergence in the response to mycobacterium bovis and mycobacterium tuberculosis infection.despite sharing >99.9% genome sequence similarity at the nucleotide level, mycobacterium tuberculosis and mycobacterium bovis-the causative agents of human and bovine tuberculosis, respectively-exhibit distinct host preferences. m. bovis can cause disease in both cattle and humans yet rarely transmits between immuno-competent human hosts, while m. tuberculosis is a highly successful pathogen of humans that does not sustain in animal populations. based on the key role played by alveolar macrophag ...201424882682
mycobacterium bovis in california dairies: a case series of 2002-2013 outbreaks.from 2002 to 2013, bovine tuberculosis (btb) caused by mycobacterium bovis (m. bovis) has been detected on numerous dairies in california. in total, twelve herds had btb detected and are included in the case series which describes these recent outbreaks and discusses potential pathways of introduction. epidemiological investigations to determine the initial source of btb in each herd included obtaining data on likely pathways of pathogen introduction. pathways included purchasing cattle, use of ...201424856878
northern ireland disease surveillance report for january to march 2014.listerial encephalitis in adult cattle oxalate nephrosis in zwartble ewes and lambs histomonosis in chickens feline tuberculosis caused by mycobacterium bovis these are among matters discussed in the northern ireland animal disease surveillance quarterly report for january to march 2014.201424853706
comparison of intervention methods for reducing human exposure to mycobacterium bovis through milk in pastoralist households of tanzania.bovine tuberculosis (btb), caused by mycobacterium bovis, is a disease of zoonotic concern, especially in countries with no control programs in livestock and where routine pasteurization of milk is not practiced. in tanzania, btb is widespread in livestock and has been diagnosed in humans; however, herd btb testing is primarily carried out for btb-free certification in commercial dairy herds at the expense of the dairy cattle owner. for rural livestock holders, such an expense is prohibitive, an ...201424853050
comparison of gene expression of immune mediators in lung and pulmonary lymph node granulomas from cattle experimentally infected with mycobacterium bovis.the cellular infiltrates and macrophage activation pathways may differ in granulomas found in the lungs and pulmonary lymph nodes of cattle infected with mycobacterium bovis. the aim of this study was to compare the histopathology and gene expression profiles of cytokines and immune mediators for cattle which had these lesions in both sites. ten friesian-cross, 15-16 month old cattle were challenged intratracheally with 5 × 10(3)cfu of virulent m. bovis and killed and necropsied at 28 weeks afte ...201424852075
characterization of mycobacterium bovis from humans and cattle in namwala district, zambia.tuberculosis remains a major public health problem in zambia. while human to human transmission of mycobacterium tuberculosis is of major importance in driving the tuberculosis epidemic, the impact of mycobacterium bovis transmission from infected cattle is largely unknown. this cross-sectional study aimed at molecular characterization of m. bovis in humans and cattle. a total of 100 human sputum samples and 67 bovine tissues were collected and analyzed for the presence of mycobacteria. of 65 hu ...201424847441
the in vivo expressed mycobacterium tuberculosis (ive-tb) antigen rv2034 induces cd4⁺ t-cells that protect against pulmonary infection in hla-dr transgenic mice and guinea pigs.tuberculosis (tb) remains a life-threatening infectious disease of global proportions with serious negative health and economic consequences. the lack of sufficient protection induced by mycobacterium bovis bcg, the current vaccine for tb, as well as the impact of hiv co-infection and the emergence of drug resistant mycobacterium tuberculosis (mtb) strains all urge for improved vaccines against tb. a minimal requirement for mtb vaccine antigens is their in vivo expression during mtb infection an ...201424837764
bacteriological diagnosis and molecular strain typing of mycobacterium bovis and mycobacterium caprae.the primary isolation of a mycobacterium sp. of the mycobacterium tuberculosis complex from an infected animal provides a definitive diagnosis of tuberculosis. however, as mycobacterium bovis and mycobacterium caprae are difficult to isolate, particularly for animals in the early stages of disease, success is dependent on the optimal performance of all aspects of the bacteriological process, from the initial choice of tissue samples at post-mortem examination or clinical samples, to the type of ...201424833269
validation of two real-time pcrs targeting the pe-pgrs 20 gene and the region of difference 4 for the characterization of mycobacterium bovis isolates.this study aimed to develop and validate real-time pcr for the diagnosis of mycobacterium bovis isolates. two hundred and seventy-four m. bovis isolates and 156 m. tuberculosis isolates were tested. both qpcrs amplified all of the 274 m. bovis samples, but none of the 156 m. tuberculosis samples. the qpcr for pe-pgrs 20 had 91% efficiency and a detection limit of 0.32 ng (sensitivity and specificity for qpcr "mbovis.100" were 99.64 and 100%, respectively). the qpcr for rd4 had 100% efficiency, a ...201425036510
disseminated bcg: complications of intravesical bladder cancer treatment.intravesical bacillus calmette-guerin (bcg) has been established as an effective treatment of superficial bladder cancer (parker and kommu, 2013). however, major side effects, including pneumonitis, sepsis, and even death, may occur in <5% of patients (gonzalez et al., 2003). here we present a case of severe disseminated mycobacterium bovis following intravesical bcg administration. our patient is a 76-year-old gentleman with newly diagnosed superficial transitional cell carcinoma of the bladder ...201425024707
bovine tuberculosis in northern ireland: risk factors associated with time from post-outbreak test to subsequent herd breakdown.compulsory bovine tuberculosis testing has been implemented since 1959 in northern ireland. initial rapid progress in the eradication of the disease was followed by a situation where disease levels tended to fluctuate around a low level. this study explores recrudescence of bovine tuberculosis (btb) in northern ireland herds by assessing risk factors associated with time from the six-month post-outbreak skin test until a further herd breakdown. bovine herds (n=3377) were recruited in 2002 and 20 ...201425023906
recombinant tb10.4 of mycobacterium bovis induces cytokine production in raw264.7 macrophages through activation of the mapk and nf-κb pathways via tlr2.the tb10.4 antigen of mycobacterium bovis/mycobacterium tuberculosis induces a strong th1 cd4+ t-cell response. thus, it is currently under intensive study as a possible vaccine candidate. however, how tb10.4 activates innate immune cells is unclear. how tb10.4 interacts with toll-like receptors (tlrs) and signaling pathways responsible for active inflammation have also not been fully elucidated. here, as stimulated raw264.7 cells with recombinant tb10.4 (rtb10.4), derived from m. bovis, increas ...201425019567
first whole-genome sequence of a clinical isolate of multidrug-resistant mycobacterium bovis bcg.the attenuated bcg strain of mycobacterium bovis is widely used as a vaccine against tuberculosis. however, in rare cases, it can be pathogenic to humans. here, we report the first draft of a whole-genome sequence of a multidrug-resistant clinical isolate of m. bovis bcg.201425013134
oleoyl coenzyme a regulates interaction of transcriptional regulator raas (rv1219c) with dna in mycobacteria.we have recently shown that raas (regulator of antimicrobial-assisted survival), encoded by rv1219c in mycobacterium tuberculosis and by bcg_1279c in mycobacterium bovis bacillus calmette-guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. here, we demonstrate that long chain acyl-coa derivatives (oleoyl-coa and, to lesser extent, palmitoyl-coa) modulate raas binding to dna and expression of the downstream genes that encode atp-dep ...201425012658
the benefits of 'one health' for pastoralists in africa.'one health' is particularly suited to serve mobile pastoralists. dinka pastoralists in sudan inspired calvin schwabe to coin the term 'one medicine', indicating that there is no difference in paradigm between human and veterinary medicine. our contemporary definition of 'one health' is any added value in terms of improved health of humans and animals or financial savings or environmental services resulting from a closer cooperation of human and animal health sectors. here we present a summary o ...201425005234
molecular characterization of mycobacterium bovis isolates from patients with tuberculosis in baja california, mexico.the incidence of tuberculosis (tb) from mycobacterium bovis in humans is likely to be underestimated and in some cases even ignored in most developing countries. this may be due to the difficulty of differentiating tb caused by either mycobacteriumtuberculosis or m. bovis. our objectives were to determine the prevalence of m. bovis human disease among the patients referred for study to the tuberculosis laboratory of the tijuana general hospital in baja california, mexico and to characterize mole ...201424997332
microrna-124 negatively regulates tlr signaling in alveolar macrophages in response to mycobacterial infection.the emerging roles of micrornas (mirnas) in regulating immune responses have attracted increasing attention in recent years; and the alveolar macrophages (ams) are the main targets of mycobacterial infection, which play a pivotal role in the pathogenesis of mycobacterium tuberculosis infection. however, the immunoregulatory role of mirnas in ams has not been fully demonstrated. in this study, we find that mir-124 is up-regulated in the peripheral leukocytes of patients with pulmonary tuberculosi ...201424995397
sharing expertise on mycobacterium bovis. 201424993712
evaluation of ethanol vortex elisa for detection of bovine tuberculosis in cattle and deer.the use of serological assays for diagnosis of bovine tuberculosis (tb) has been intensively studied and use of specific antigens have aided in improving the diagnostic accuracy of the assays. in the present study, we report an in-house enzyme linked immunosorbent assay (elisa), developed by using ethanol extract of mycobacterium bovis (m. bovis). the assay, named (ethanol vortex elisa [evelisa]), was evaluated for detection of anti- m. bovis antibodies in the sera of cattle and white-tailed dee ...201424992970
immunodeficiency associated with a nonsense mutation of ikbkb.we report an infant of consanguineous parents of turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding inhibitor of nuclear factor kappa-b (nf-κb) kinase subunit beta (ikkβ). at five months, she presented with respiratory insufficiency and pneumocystis jirovecii pneumonia which was successfully treated. at nine months, iatrogenic systemic infection with mycobacterium bovis was found and eventually led to her death at age 14 months. ...201425216719
impact of in vitro evolution on antigenic diversity of mycobacterium bovis bacillus calmette-guerin (bcg).mycobacterium bovis bacillus calmette-guerin (bcg), the only vaccine currently used against tuberculosis, is an attenuated derivative of m. bovis that has been propagated in vitro for more than 40 years. we have previously reported that the experimentally-verified human t cell epitopes of the m. tuberculosis complex (mtbc) are the most conserved elements of the genome; whether immune recognition is the force driving the conservation of epitopes in the mtbc is unknown. therefore, we sequenced the ...201425211768
mycobacterium bovis bcg promotes tumor cell survival from tumor necrosis factor-α-induced apoptosis.increased incidence of lung cancer among pulmonary tuberculosis patients suggests mycobacteria-induced tumorigenic response in the host. the alveolar epithelial cells, candidate cells that form lung adenocarcinoma, constitute a niche for mycobacterial replication and infection. we thus explored the possible mechanism of m. bovis bacillus calmette-guérin (bcg)-assisted tumorigenicity in type ii epithelial cells, human lung adenocarcinoma a549 and other cancer cells.201425208737
bovine tuberculosis surveillance in cattle and free-ranging wildlife in eu member states in 2013: a survey-based review.bovine tuberculosis (tb) is a common disease in cattle and wildlife, with animal health, zoonotic and economic impacts. most of the tb data for the european union (eu) concern the epidemiological situation, but comprehensive descriptions of the way in which surveillance is conducted in each country are rare, despite being essential for cross-europe comparisons. a european survey was conducted in the 28 member states and in three other neighboring countries (norway, macedonia and switzerland), to ...201425205200
gene deletions in mycobacterium bovis bcg stimulate increased cd8+ t cell responses.mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host's immune response. it has been suggested that mycobacteria may contain genes that reduce the host's ability to elicit cd8(+) t cell responses. we screened 3,290 mutant mycobacterium bovis bacillus calmette guerin (bcg) strains to identify genes that decrease major histocompatibility complex (mhc) class i presentation of mycobacterium ...201425287928
mycobacterium bovis in burkina faso: epidemiologic and genetic links between human and cattle isolates.in sub-saharan africa, bovine tuberculosis (btb) is a potential hazard for animals and humans health. the goal of this study was to improve our understanding of btb epidemiology in burkina faso and especially mycobacterium bovis transmission within and between the bovine and human populations.201425275305
a new recombinant bcg vaccine induces specific th17 and th1 effector cells with higher protective efficacy against tuberculosis.tuberculosis (tb) is an infectious disease caused by mycobacterium tuberculosis (mtb) that is a major public health problem. the vaccine used for tb prevention is mycobacterium bovis bacillus calmette-guérin (bcg), which provides variable efficacy in protecting against pulmonary tb among adults. consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of bcg. here we constructed a new recombinant bcg (rbcg) vaccine expressing a fusion ...201425398087
field evaluation of three blood-based assays for elk (cervus canadensis) naturally infected with mycobacterium bovis.diagnosis of mycobacterium bovis in wild populations is very challenging due to complications imposed by the use of traditional skin tests, poor sensitivity of gold standard tests which rely on culture of m. bovis from tissues and wide variations in severity of disease. various combinations of a lymphocyte stimulation test (lst), fluorescence polarization assay (fpa) and the cervid tb stat-pak were evaluated using two different validation approaches: a latent class analysis and classical statist ...201424315383
anti-mycobacterial activities of synthetic cationic α-helical peptides and their synergism with rifampicin.the rapid emergence of multi-drug resistant tuberculosis (tb) and the lack of effective therapies have prompted the development of compounds with novel mechanisms of action to tackle this growing public health concern. in this study, a series of synthetic cationic α-helical antimicrobial peptides (amps) modified with different hydrophobic amino acids was investigated for their anti-mycobacterial activity, both alone and in synergistic combinations with the frontline anti-tuberculosis drug rifamp ...201424314557
binding pocket alterations in dihydrofolate synthase confer resistance to para-aminosalicylic acid in clinical isolates of mycobacterium tuberculosis.the mechanistic basis for the resistance of mycobacterium tuberculosis to para-aminosalicylic acid (pas), an important agent in the treatment of multidrug-resistant tuberculosis, has yet to be fully defined. as a substrate analog of the folate precursor para-aminobenzoic acid, pas is ultimately bioactivated to hydroxy dihydrofolate, which inhibits dihydrofolate reductase and disrupts the operation of folate-dependent metabolic pathways. as a result, the mutation of dihydrofolate synthase, an enz ...201424366731
current knowledge and pending challenges in zoonosis caused by mycobacterium bovis: a review.mycobacterium bovis is both the causative agent of bovine tuberculosis (tb) and a zoonotic pathogen. in humans, considerably fewer cases of tb are caused by m. bovis than m. tuberculosis; nevertheless, diagnostic limitations mean that currently available data on prevalence grossly underestimate the true dimension of the problem. the routes of transmission from animals to humans are well known and include direct exposure to infected animals or consumption of contaminated animal products. applicat ...201424360647
innate defects of the il-12/ifn-γ axis in susceptibility to infections by mycobacteria and salmonella.since 1996, several studies characterizing the association between primary immunodeficiencies and susceptibility to infections with environmental and non-pathogenic mycobacteria such as the bacillus calmette-guérin (mycobacterium bovis bacillus of calmette guérin strain) as well as disseminated infections by salmonella spp. have been conducted. these conditions, grouped in the so-called mendelian susceptibility to mycobacterial diseases, include a primary immunodeficiency caused by mutations in ...201424359575
targeting lipid esterases in mycobacteria grown under different physiological conditions using activity-based profiling with tetrahydrolipstatin (thl).tetrahydrolipstatin (thl) is bactericidal but its precise target spectrum is poorly characterized. here, we used a thl analog and activity-based protein profiling to identify target proteins after enrichment from whole cell lysates of mycobacterium bovis bacillus calmette-guérin cultured under replicating and non-replicating conditions. thl targets α/β-hydrolases, including many lipid esterases (lipd, g, h, i, m, n, o, v, w, and tesa). target protein concentrations and total esterase activity co ...201424345785
double recombinant mycobacterium bovis bcg strain for screening of primary and rationale-based antimycobacterial compounds.conventional antimycobacterial screening involves cfu analysis, which poses a great challenge due to slow growth of mycobacteria. recombinant strains carrying reporter genes under the influence of constitutive promoters allow rapid and wide screening of compounds but without revealing their modes of action. reporter strains using pathway-specific promoters provide a better alternative but allow a limited screening of compounds interfering with only a particular metabolic pathway. this reduces th ...201424342633
killed but metabolically active mycobacterium bovis bacillus calmette-guérin retains the antitumor ability of live bacillus calmette-guérin.mycobacterium bovis bacillus calmette-guérin is the most effective treatment for high risk noninvasive bladder cancer. although bacillus calmette-guérin immunotherapy clearly decreases recurrence and progression rates, side effects are common and infection with the bacillus has been described. for these reasons it is necessary to find safer alternatives to the live bacillus. we explored the possibility of using killed but metabolically active bacillus calmette-guérin.201424333111
the bcg moreau rd16 deletion inactivates a repressor reshaping transcription of an adjacent gene.the brazilian anti-tuberculosis vaccine strain mycobacterium bovis bacillus calmette-guérin (bcg) bcg moreau is unique in having a deletion of 7608 bp (rd16) that results in the truncation of a putative tetr transcriptional regulator, the ortholog of mycobacterium tuberculosis rv3405c, bcg_m3439c. we investigated the effect of this truncation on the expression of the rv3406 ortholog (bcg_m3440), lying 81 bp downstream in the opposite orientation. rt-pcr and western blot experiments show that rv3 ...201424332305
identification of the target protein of agelasine d, a marine sponge diterpene alkaloid, as an anti-dormant mycobacterial substance.one of the major reasons for the wide epidemicity of tuberculosis and for the necessity for extensive chemotherapeutic regimens is that the causative agent, mycobacterium tuberculosis, has an ability to become dormant. therefore, new lead compounds that are anti-bacterial against m. tuberculosis in both active and dormant states are urgently needed. marine sponge diterpene alkaloids, agelasines b, c, and d, from an indonesian marine sponge of the genus agelas were rediscovered as anti-dormant-my ...201424243718
evaluation of single and comparative intradermal tuberculin tests for tuberculosis eradication in caprine flocks in castilla y león (spain).goats can act as reservoirs for tuberculosis (tb) infection. the main etiological agents of tb in goats are mycobacterium caprae and mycobacterium bovis and they infect also a wide range of domestic and wild animals and humans. control programmes based mainly on the application of single and comparative intradermal tuberculin (sit and scit respectively) tests are being implemented in certain regions of spain with a high density of caprine flocks as castilla y león, including goats with epidemiol ...201424239314
use of antigen-specific interleukin-2 to differentiate between cattle vaccinated with mycobacterium bovis bcg and cattle infected with m. bovis.we describe here the application of a novel bovine interleukin-2 (il-2) enzyme-linked immunosorbent assay (elisa) for the measurement of antigen-specific il-2 in cattle naturally infected with mycobacterium bovis and in cattle vaccinated with mycobacterium bovis bcg and then experimentally challenged with pathogenic m. bovis. supernatants from whole-blood cultures stimulated with mycobacterial antigen (bovine purified protein derivative [ppdb] or the peptide cocktail esat6-cfp10) were assessed u ...201424173026
utility of a fecal real-time pcr protocol for detection of mycobacterium bovis infection in african buffalo (syncerus caffer).a real-time pcr protocol for detecting mycobacterium bovis in feces was evaluated in bovine tuberculosis-infected african buffalo (syncerus caffer). fecal samples spiked with 1.42 × 10(3) cells of m. bovis culture/g and bacille calmette-guérin standards with 1.58 × 10(1) genome copies/well were positive by real-time pcr but all field samples were negative.201424171565
comparison of the immunogenicity and protection against bovine tuberculosis following immunization by bcg-priming and boosting with adenovirus or protein based vaccines.there is a requirement for vaccines or vaccination strategies that confer better protection against tb than the current live attenuated mycobacterium bovis bacillus calmette-guerin (bcg) vaccine for use in cattle. boosting with recombinant viral vectors expressing mycobacterial proteins, such as ag85a, has shown a degree of promise as a strategy for improving on the protection afforded by bcg. experiments in small animal models have indicated that broadening the immune response to include mycoba ...201424269321
genotypic characterization by spoligotyping and vntr typing of mycobacterium bovis and mycobacterium caprae isolates from cattle of tunisia.this work is an approach to the molecular epidemiology of mycobacterium tuberculosis complex (mtbc) bovine infections in tunisia. a total of 35 mtbc isolates from both lateral retropharyngeal lymph node samples of cattle slaughtered in different tunisian regions were genotyped by spoligotyping and variable number tandem repeat typing (vntr)-typing. spoligotyping allowed to identify two profiles not previously registered, namely sb2024, a mycobacterium caprae isolate from nabeul region (north eas ...201424158359
efficient activation of human t cells of both cd4 and cd8 subsets by urease-deficient recombinant mycobacterium bovis bcg that produced a heat shock protein 70-m. tuberculosis-derived major membrane protein ii fusion protein.for the purpose of obtaining mycobacterium bovis bacillus calmette-guérin (bcg) capable of activating human naive t cells, urease-deficient bcg expressing a fusion protein composed of mycobacterium tuberculosis-derived major membrane protein ii (mmp-ii) and heat shock protein 70 (hsp70) of bcg (bcg-dhtm) was produced. bcg-dhtm secreted the hsp70-mmp-ii fusion protein and effectively activated human monocyte-derived dendritic cells (dcs) by inducing phenotypic changes and enhanced cytokine produc ...201424152387
isolation and molecular characterization of mycobacterium bovis from kafue lechwe (kobus leche kafuensis) from zambia.bovine tuberculosis (btb) is a chronic bacterial disease caused by mycobacterium bovis. infections due to m. bovis, which serves as a stable reservoir, can pose serious challenge to control and eradicate in both wildlife and livestock at the interface. this study aimed at isolating and characterizing m. bovis from kafue lechwe (kobus leche kafuensis) and black lechwe (kobus leche smithemani) at the animal/human interface in zambia. the samples with lesions compatible with btb collected during th ...201424146292
[severe disseminated mycobacterium bovis bcg infection as a consequence of intravesical bcg therapy: diagnostic challenges and therapeutic options].we present the case of a 65-year-old patient with superficial carcinoma of the bladder who developed systemic inflammatory reaction as a result of a severe disseminated infection with m. bovis bcg after intravesical instillation of bcg. besides the recommended antituberculosis therapy, considering the resistance of m. bovis to pza, we discuss here the option of using steroids in the therapeutic management of this patient.201424824462
characterization of a novel necrotic granuloma model of latent tuberculosis infection and reactivation in mice.we sought to develop and characterize a novel paucibacillary model in mice, which develops necrotic lung granulomas after infection with mycobacterium tuberculosis. six weeks after aerosol immunization with recombinant mycobacterium bovis bacillus calmette-guerin overexpressing the 30-kda antigen, c3heb/fej mice were aerosol infected with m. tuberculosis h37rv. six weeks later, mice were treated with one of three standard regimens for latent tuberculosis infection or tumor necrosis factor (tnf)- ...201424815353
subclinical miliary mycobacterium bovis following bcg immunotherapy for transitional cell carcinoma of the bladder.the authors present an unusual case of a 51-year-old man who developed relatively mild non-specific symptoms following intravesical bcg instillation for superficial transitional cell carcinoma of the bladder, with radiological investigations demonstrating typical features of miliary tuberculosis (tb). transbronchial biopsy showed small foci of poorly formed granuloma suggestive of mycobacterium infection. the patient's respiratory symptoms only became apparent 7 days after discharge having had 4 ...201424811557
agreement between assays of cell-mediated immunity utilizing mycobacterium bovis-specific antigens for the diagnosis of tuberculosis in african buffaloes (syncerus caffer).we assessed the use of mycobacterium bovis-specific peptides for the diagnosis of tuberculosis in african buffaloes (syncerus caffer) by evaluating the agreement between the single intradermal comparative tuberculin test (sictt), the bovigam(®) ec (bec) assay, the bovigam(®) hp (bhp) assay and two assays utilizing the quantiferon(®) tb-gold (in tube) system employing 20 h (mqft20 assay) and 30 h (mqft30 assay) whole blood incubation periods. of 84 buffaloes, 45% were sictt-positive, 48% were bec ...201424794136
oral vaccination of badgers (meles meles) against tuberculosis: comparison of the protection generated by bcg vaccine strains pasteur and danish.vaccination of badgers by the subcutaneous, mucosal and oral routes with the pasteur strain of mycobacterium bovis bacille calmette-guérin (bcg) has resulted in significant protection against experimental infection with virulent m. bovis. however, as the bcg danish strain is the only commercially licensed bcg vaccine for use in humans in the european union it is the vaccine of choice for delivery to badger populations. as all oral vaccination studies in badgers were previously conducted using th ...201424792450
experimental selection of long-term intracellular mycobacteria.some intracellular bacteria are known to cause long-term infections that last decades without compromising the viability of the host. although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long-term intracellular lifestyle. selected mycobacterium bovis bcg through continuous culture in ma ...201424779357
recombinant bcg: innovations on an old vaccine. scope of bcg strains and strategies to improve long-lasting memory.bacille calmette-guérin (bcg), an attenuated vaccine derived from mycobacterium bovis, is the current vaccine of choice against tuberculosis (tb). despite its protection against active tb in children, bcg has failed to protect adults against tb infection and active disease development, especially in developing countries where the disease is endemic. currently, there is a significant effort toward the development of a new tb vaccine. this review article aims to address publications on recombinant ...201424778634
current ante-mortem techniques for diagnosis of bovine tuberculosis.bovine tuberculosis (tb), mainly caused by mycobacterium bovis, is a zoonotic disease with implications for public health and having an economic impact due to decreased production and limitations to the trade. bovine tb is subjected to official eradication campaigns mainly based on a test and slaughter policy using diagnostic assays based on the cell-mediated immune response as the intradermal tuberculin test and the gamma-interferon (ifn-γ) assay. moreover, several diagnostic assays based on th ...201424768355
mycobacterium indicus pranii and mycobacterium bovis bcg lead to differential macrophage activation in toll-like receptor-dependent manner.mycobacterium indicus pranii (mip) is an atypical mycobacterial species possessing strong immunomodulatory properties. it is a potent vaccine candidate against tuberculosis, promotes th1 immune response and protects mice from tumours. in previous studies, we demonstrated higher protective efficacy of mip against experimental tuberculosis as compared with bacillus calmette-guérin (bcg). since macrophages play an important role in the pathology of mycobacterial diseases and cancer, in the present ...201424766519
evaluation of molecular markers for the diagnosis of mycobacterium bovis.mycobacterium tuberculosis complex (mtc) comprises a group of bacteria that have a high degree of genetic similarity. two species in this group, mycobacterium tuberculosis and mycobacterium bovis, are the main cause of human and bovine tuberculosis, respectively. m. bovis has a broader host range that includes humans; thus, the differentiation of mycobacterium is of great importance for epidemiological and public health considerations and to optimize treatment. the current study aimed to evaluat ...201424744007
a mycobacterium bovis bcg-naked dna prime-boost vaccination strategy induced cd4⁺ and cd8⁺ t-cell response against mycobacterium tuberculosis immunogens.mycobacterium tuberculosis infection is still a major global public health problem. presently the only tuberculosis (tb) vaccine available is bacille calmette-guérin (bcg), although it fails to adequately protect against pulmonary tb in adults. to solve this problem, the development of a new effective vaccine is urgently desired. bcg-prime dna-booster vaccinations strategy has been shown to induce greater protection against tuberculosis (tb) than bcg alone. some studies have demonstrated that th ...201424741595
a polymerase chain reaction and enzyme linked immunosorbent assay based approach for diagnosis and differentiation between vaccinated and infected cattle with mycobacterium bovis.in most african and arabic countries tuberculosis (tb) causes great economic losses in bovine species and constitutes serious zoonotic problem. as the traditional diagnostic method delay the research because of low sensitivity and specificity, a rapid method of diagnosis is of outmost importance.201424741280
maturation of innate responses to mycobacteria over the first nine months of life.newborns and young infants are particularly susceptible to infections, including mycobacterium tuberculosis. further, immunogenicity of vaccines against tuberculosis and other infectious diseases appears suboptimal early in life compared with later in life. we hypothesized that developmental changes in innate immunity would underlie these observations. to determine the evolution of innate responses to mycobacteria early in life, whole blood or pbmc from newborns, as well as 10- and 36-wk-old inf ...201424733845
high-throughput multiplex miru-vntr typing of mycobacterium bovis.spoligotyping is the most widely used method for genotyping mycobacterium bovis (m. bovis). however, its discriminatory power varies widely between countries. miru-vntr typing could be a promising alternative, although it generally requires the time consuming and laborious simplex pcr assays using standard agarose gel electrophoresis. the accuracy of this approach depends on good standardization and a certain degree of expertise. this study presents a version of miru-vntr based on three triplex ...201424726022
mycobacterium bovis infection in cats and people. 201424722605
mycobacterium bovis infection in cats and people. 201424722604
cd8+ regulatory t cells, and not cd4+ t cells, dominate suppressive phenotype and function after in vitro live mycobacterium bovis-bcg activation of human cells.mycobacterium bovis bacillus calmette-guérin (m. bovis bcg), the only currently available vaccine against tuberculosis, has been reported to induce regulatory t cells in humans. the activity of regulatory t cells may not only dampen immunogenicity and protective efficacy of tuberculosis-vaccines, but also hamper diagnosis of infection of tuberculosis, when using immune (e.g. ifnγ-release) assays. still, in settings of infectious diseases and vaccination, most studies have focused on cd4+ regulat ...201424714620
challenges to improve the stability and efficacy of an intravesical bcg product.the aim of this investigation was to improve the storage stability and survival rate of an intravesical bcg product, manufactured with an attenuated strain of mycobacterium bovis (pasteur strain 1173p2 of bcg) in the presence of sodium glutamate. formulations with various concentrations of trehalose (a known protectant) were developed as liquid and lyophilized forms. formulations were evaluated by different methods, including optical density measurement, safety assessment, skin reaction test, mo ...201424711840
myd88 signalling in myeloid cells is sufficient to prevent chronic mycobacterial infection.tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis that is responsible for almost 1.5 million deaths per year. sensing of mycobacteria by the host's immune system relies on different families of receptors present on innate immune cells. amongst them, several members of the tlr family are involved in the activation of immune cells by mycobacteria, yet the in vivo contribution of individual tlrs to the protective immune response remains controversial. on the contrary ...201424435955
mycobacterium bovis bcg infection severely delays trichuris muris expulsion and co-infection suppresses immune responsiveness to both pathogens.the global epidemiology of parasitic helminths and mycobacterial infections display extensive geographical overlap, especially in the rural and urban communities of developing countries. we investigated whether co-infection with the gastrointestinal tract-restricted helminth, trichuris muris, and the intracellular bacterium, mycobacterium bovis (m. bovis) bcg, would alter host immune responses to, or the pathological effect of, either infection.201424433309
long-term survival of tuberculosis complex mycobacteria in soil.while there is evidence for the persistence of mycobacterium bovis in soil, there are no reports for the other mycobacterium tuberculosis complex (mtc) mycobacteria. here, soil was inoculated with 10(8) c.f.u. g(-1) m. tuberculosis, m. bovis and m. canettii and subcultured monthly for 12 months. the pathogenicity of mycobacterial colonies, identified by using matrix-assisted laser desorption/ionization time of flight mass spectrometry, was assessed in a mouse model. moreover, mice were fed with ...201424425768
evaluating the tuberculosis hazard posed to cattle from wildlife across europe.tuberculosis (tb) caused by infection with mycobacterium bovis (m. bovis) and other closely related members of the m. tuberculosis complex (mtc) infects many domestic and wildlife species across europe. transmission from wildlife species to cattle complicates the control of disease in cattle. by determining the level of tb hazard for which a given wildlife species is responsible, the potential for transmission to the cattle population can be evaluated. we undertook a quantitative review of tb ha ...201424423727
physical characterization of synthetic phosphatidylinositol dimannosides and analogues in binary systems with phosphatidylcholine.native phosphatidylinositol mannosides (pims) from the cell wall of mycobacterium bovis (m. bovis) and synthetic analogues have been identified to exert immunostimulatory activities. these activities have been investigated using particulate delivery systems containing native mannosylated lipids or total lipid extracts. limited work has been carried out examining the incorporation of individual pim lipids into suitable particulate formulations such as liposomes. the present study explored the pos ...201424423066
early detection of mycobacteria using a novel hydrogel culture method.early laboratory detection of mycobacterium tuberculosis is crucial for controlling tuberculosis. we developed a hydrogel mycobacterial culture method that retains the advantages of both solid and liquid methods in terms of speed, cost, and efficiency.201424422192
a novel synthetic mycolic acid inhibits bronchial hyperresponsiveness and allergic inflammation in a mouse model of asthma.recognition of microbes is important to trigger the innate immune system. mycolic acid (ma) is a component of the cell walls of mycobacteria such as mycobacterium bovis bacillus calmette-guerin. ma has immunogenic properties, which may modulate the innate and adaptive immune response. this study aimed to investigate whether a novel synthetic ma (sma) inhibits allergic inflammatory responses in a mouse model of asthma.201424404398
evaluation of the aid tb resistance line probe assay for rapid detection of genetic alterations associated with drug resistance in mycobacterium tuberculosis strains.the rapid accurate detection of drug resistance mutations in mycobacterium tuberculosis is essential for optimizing the treatment of tuberculosis and limiting the emergence and spread of drug-resistant strains. the tb resistance line probe assay from autoimmun diagnostika gmbh (aid) (strassburg, germany) was designed to detect the most prevalent mutations that confer resistance to isoniazid, rifampin, streptomycin, amikacin, capreomycin, fluoroquinolones, and ethambutol. this assay detected resi ...201424403306
association between spoligotype-vntr types and virulence of mycobacterium bovis in cattle.mycobacterium bovis is the causative agent of bovine tuberculosis, a disease that affects approximately 5% of argentine cattle. the aim of this research was to study if it is possible to infer the degree of virulence of different m. bovis genotypes based on scorified observations of tuberculosis lesions in cattle. in this study, we performed association analyses between several parameters with tuberculosis lesions: m. bovis genotype, degree of progression of tuberculosis, and animal age. for thi ...201424398919
bcg δzmp1 vaccine induces enhanced antigen specific immune responses in cattle.mycobacterium bovis (m. bovis) causes major economy and public health problem in numerous countries. in great britain, despite the use of a test-and-slaughter strategy, the incidence of bovine tuberculosis (btb) in cattle has steadily risen in recent years. one strategy being considered to reduce the burden of btb in cattle is the development of an efficient vaccine. the only current potentially available vaccine against tuberculosis, live attenuated m. bovis bacille calmette-guérin (bcg), has d ...201424394444
key role of effector memory cd4+ t lymphocytes in a short-incubation heparin-binding hemagglutinin gamma interferon release assay for the detection of latent tuberculosis.the treatment of latent tuberculosis infection (ltbi) in target populations is one of the current who strategies for preventing active tuberculosis (tb) infection and reducing the mycobacterium tuberculosis reservoir. therefore, powerful ltbi screening tools are indispensable. a gamma interferon release assay (igra) in response to the stimulation of peripheral blood mononuclear cells by the latency antigen native heparin-binding hemagglutinin (nhbha-igra) has proven its potential for this purpos ...201424391135
nanoparticulation of bcg-cws for application to bladder cancer therapy.the mycobacterium bovis bacille calmette-guerin cell wall skeleton (bcg-cws) could be used to replace live bcg as a bladder cancer drug. however, because bcg-cws is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. we report herein on the development of a novel packaging method that permits bcg-cws to be encapsulated into 166nm-sized lipid particles. the bcg-cws encapsulated nano particle (c ...201424389133
an immunomodulatory role for the mycobacterium tuberculosis region of difference 1 locus proteins pe35 (rv3872) and ppe68 (rv3873).the pathogenesis of mycobacterium tuberculosis involves the coordinate action of multiple bacillary components that modulate host immune responses to ensure its survival. one such group of factors is the multigenic pe_ppe protein family, several members of which have been implicated in host immune evasion. here we investigate the function of the pe-ppe gene pair pe35 (rv3872)-ppe68 (rv3873), located in the region of difference 1, encoding a specialized mycobacterial secretion system that is dele ...201424467650
tlr3 regulates mycobacterial rna-induced il-10 production through the pi3k/akt signaling pathway.cytokine induction in response to mycobacterium tuberculosis (mtb) infection is critical for pathogen control, by (i) mediating innate immune effector functions and (ii) instructing specific adaptive immunity. il-10 is an important anti-inflammatory cytokine involved in pathogenesis of tuberculosis (tb). here, we show that tlr3, a sensor of extracellular viral or host rna with stable stem structures derived from infected or damaged cells, is essential for mtb-induced il-10 production. upon mycob ...201424462705
analysis of mirna expression profiling in human macrophages responding to mycobacterium infection: induction of the immune regulator mir-146a.the regulatory mechanism of microrna (mirna) within macrophage innative response to mycobacterium tuberculosis infection is not clear yet.201424462562
evidence of presence of mycobacterium tuberculosis in bovine tissue samples by multiplex pcr: possible relevance to reverse zoonosis.bovine tuberculosis, caused by mycobacterium bovis, remains one of the most important zoonotic health concerns worldwide. the transmission of mycobacterium tuberculosis from humans to animals also occurs especially in countries where there is close interaction of humans with the animals. in the present study, thirty bovine lung tissue autopsy samples from an organized dairy farm located in north india were screened for the presence of mycobacterium tuberculosis complex by smear microscopy, histo ...201424456326
extent of mycobacterium bovis infection in dairy cattle herds subject to partial culling as determined by an interferon-gamma assay.the interferon-gamma (ifn-γ) assay is employed as a complementary diagnostic test for bovine tuberculosis (btb) in many countries. to simplify this assay, we established a 96-well plate format using the esat-6 and cfp-10 antigens and then employed it to determine the extent of mycobacterium (m.) bovis infection in dairy herds with a history of btb outbreaks in a country where only selective culling is practiced. the sensitivity and specificity of this ifn-γ assay were 85.9% and 100%, respectivel ...201424378586
microrna-149 negatively regulates tlr-triggered inflammatory response in macrophages by targeting myd88.micrornas (mirnas) have been shown to be important regulators of tlr signaling pathway at the post-transcriptional level. in this study, the potential role of mir-149 was explored in murine alveolar macrophage raw264.7 cells. our results demonstrated a dynamic change of the expressions of mir-149 expression and myd88 in macrophage raw264.7 upon mycobacterium bovis bacillus calmette-guerlin (bcg) infection or lipopolysaccharide (lps) stimulation. the presence of bcg or lps dynamically reduced the ...201424375488
assessment of t cell response to novel mycobacterium tuberculosis synthetic overlapping peptides mixtures (rv2659 and rv2660) and esat-6 in egyptian patients.tuberculosis (tb) remains one of the major challenges to the global public health. the most powerful tools in any tb control program are prompt diagnosis and successful treatment of patients with active contagious disease. for almost 100 years the tuberculin skin test (tst) has been used to support the diagnosis of active and latent tb infection. the tst has a number of limitations, most notable low specificity in bcg vaccinated individuals due to cross-reactive components in ppd and the mycobac ...201425812354
mycobacterium bovis bcg killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. regulatory t cells (tregs) and il-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. we have previously shown that mycobacterium bovis bcg killed by extended freeze-drying (efd bcg) decreases lung and colon inflammation by recruiting il-10-producing tregs. therefore, the aim of this study was to investigate the e ...201423962000
synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1-substituted indole-3-carboxaldehydes.a series of novel thiocarbohydrazones of substituted indoles and their corresponding thiadiazole derivatives were prepared, and their structures were confirmed by different analytical and spectroscopic methods. the derivatives were prepared by a sequential synthetic strategy including substitution at n-1 position of indole ring by various aliphatic and benzylic substituents, followed by condensation with thiocarbohydrazide, and finally cyclization by triethyl orthoformate. the derivatives were t ...201424103309
evaluation of the interferon-γ assay on blood collected at exsanguination of cattle under field conditions for surveillance of bovine tuberculosis.development of point of concentration (poc) surveillance strategies for bovine tuberculosis (btb) would facilitate global efforts to eradicate btb. the interferon-gamma (ifnγ) assay can detect ifnγ responses to mycobacterium bovis in blood collected at commencement of exsanguination (coe) of experimentally challenged cattle but has not been evaluated under field conditions. the current study was aimed at determining (i) whether blood collected at coe of cattle at slaughter, under field condition ...201423522063
mycobacterium bovis: a rare cause of hand tenosynovitis. 201423340760
differential tlr2 downstream signaling regulates lipid metabolism and cytokine production triggered by mycobacterium bovis bcg infection.the nuclear receptor pparγ acts as a key modulator of lipid metabolism, inflammation and pathogenesis in bcg-infected macrophages. however, the molecular mechanisms involved in pparγ expression and functions during infection are not completely understood. here, we investigate signaling pathways triggered by tlr2, the involvement of co-receptors and lipid rafts in the mechanism of pparγ expression, lipid body formation and cytokine synthesis in macrophages during bcg infection. bcg induces nf-κb ...201424120921
evaluation of protective efficacy conferred by a recombinant mycobacterium bovis bcg expressing a fusion protein of ag85a-esat-6.we previously constructed a recombinant bacille calmette-guérin (rbcg-ae) strain that could express a fused ag85a-esat-6 protein. that study suggested that the rbcg-ae strain was able to induce a higher titer of antibody and elicit a more long-lived and stronger th1-type cellular immune responses than the parental bcg strain, the rbcg-a strain (i.e., expressing ag85a), or the rbcg-e strain (i.e., expressing esat-6).201423357605
persistence of mycobacterium bovis bacillus calmette-guérin (bcg) danish in white-tailed deer (odocoileus virginianus) vaccinated with a lipid-formulated oral vaccine.mycobacterium bovis, the causative agent of tuberculosis in animals, has a broad host range, including humans. historically, public health concerns prompted programs to eradicate tuberculosis from cattle in many nations. eradication efforts decreased the prevalence of bovine tuberculosis; nevertheless, some countries encountered significant obstacles, not least of which was a wildlife reservoir of m. bovis. efforts to decrease the size of the affected wildlife populations have neither eliminated ...201423173832
genetics of mycobacterial arabinogalactan and lipoarabinomannan assembly.the cell wall of mycobacterium tuberculosis is unique in that it differs significantly from those of both gram-negative and gram-positive bacteria. the thick, carbohydrate- and lipid-rich cell wall with distinct lipoglycans enables mycobacteria to survive under hostile conditions such as shortage of nutrients and antimicrobial exposure. the key features of this highly complex cell wall are the mycolyl-arabinogalactan-peptidoglycan (magp)-based and phosphatidyl-myo-inositol-based macromolecular s ...201426104198
bovine tuberculosis in rwanda: prevalence and economic impact evaluation by meat inspection at société des abattoirs de nyabugogo-nyabugogo abattoir, kigali.despite the significant public health burden of bovine tuberculosis (btb) in rwanda, the prevalence of btb is poorly documented. this study was conducted to estimate the prevalence of btb in cattle using gross examination of granulomatous lesions, to identify mycobacteria species in suspected samples, and to evaluate the economic impact of meat condemnation based on btb-like lesions in the meat industry in rwanda. routine meat inspection was conducted at société des abattoirs de nyabugogo (saban ...201425685979
wrist tenosynovitis due to mycobacterium bovis infection: case series and review of the literature.tuberculosis infections are still one of the most important public health problems among developing countries. musculoskeletal involvement represents 10-15% of all extrapulmonary cases. tuberculosis tenosynovitis is usually misdiagnosed as nonspecific tenosynovitis. to avoid misdiagnosis and mistreatment, it is important to be alert for mycobacterial infections. this article presents 3 patients with wrist tenosynovitis, which was caused by mycobacterium bovis infection. the article also includes ...201425587496
pcr-based genomic deletion analysis of rd-regions in the identification of mycobacteria isolated from adverse events following bcg vaccination or tb suspected cases.early identification of mycobacterial species is crucial for early diagnosis. pcr-multiplex method performed on randomly chosen 54 mycobacteria isolates originating from clinical samples was found to be an inexpensive, quick and reliable alternative for commercially available diagnostics tests. although the results of gene probes identification performed by ntldr were generally consistent with multiplex pcr, two mixed mycobacterium bovis bcg/mycobacterium tuberculosis infections and a single mis ...201425546948
identification of single nucleotide polymorphisms in toll-like receptor candidate genes associated with tuberculosis infection in water buffalo (bubalus bubalis).toll-like receptors play a key role in innate immunity by recognizing pathogens and activating appropriate responses. pathogens express several signal molecules (pathogen-associated molecular patterns, pamps) essential for survival and pathogenicity. recognition of pamps triggers an array of anti-microbial immune responses through the induction of various inflammatory cytokines. the objective of this work was to perform a case-control study to characterize the distribution of polymorphisms in th ...201425496717
spatial dynamics of bovine tuberculosis in the autonomous community of madrid, spain (2010-2012).progress in control of bovine tuberculosis (btb) is often not uniform, usually due to the effect of one or more sometimes unknown epidemiological factors impairing the success of eradication programs. use of spatial analysis can help to identify clusters of persistence of disease, leading to the identification of these factors thus allowing the implementation of targeted control measures, and may provide some insights of disease transmission, particularly when combined with molecular typing tech ...201425536514
the evaluation of candidate biomarkers of cell-mediated immunity for the diagnosis of mycobacterium bovis infection in african buffaloes (syncerus caffer).we evaluated commercially available bovine enzyme linked immunosorbent assays (elisa) and a human ip-10 elisa to measure ip-10, mig, mcp-1, mcp-2, mcp-3 and il1-ra in buffalo plasma in order to identify sensitive markers of the immune response to mycobacterium bovis-specific peptides. additionally, we found that all coding mrna sequences of these cytokines showed very high homology with their homologues in domestic cattle (97-99%) as did the derived amino acid sequences (97-99%). this high seque ...201425464825
potent antimycobacterial activity of the pyridoxal isonicotinoyl hydrazone analog 2-pyridylcarboxaldehyde isonicotinoyl hydrazone: a lipophilic transport vehicle for isonicotinic acid hydrazide.the rise in drug-resistant strains of mycobacterium tuberculosis is a major threat to human health and highlights the need for new therapeutic strategies. in this study, we have assessed whether high-affinity iron chelators of the pyridoxal isonicotinoyl hydrazone (pih) class can restrict the growth of clinically significant mycobacteria. screening a library of pih derivatives revealed that one compound, namely, 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (pcih), exhibited nanomolar in vitro ...201424243647
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