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anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of melophlus sp.tuberculosis (tb), caused by mycobacterium tuberculosis infection, is a major world health problem that is responsible for the deaths of 1.5 million people each year. in addition, the requirement for long-term therapy to cure tb complicates treatment of the disease. one of the major reasons for the extended chemotherapeutic regimens and wide epidemicity of tb is that m. tuberculosis has the ability to persist in a dormant state. we therefore established a new screening system to search for subst ...201627193014
triclosan-induced genes rv1686c-rv1687c and rv3161c are not involved in triclosan resistance in mycobacterium tuberculosis.a key issue towards developing new chemotherapeutic approaches to fight mycobacterium tuberculosis is to understand the mechanisms underlying drug resistance. previous studies have shown that genes rv1686c-rv1687c and rv3161c, predicted to encode an atp-binding cassette transporter and a dioxygenase respectively, are induced in the presence of triclosan and other antimicrobial compounds. therefore a possible role in drug resistance has been suggested for the products of these genes although no f ...201627193696
standard genotyping overestimates transmission of mycobacterium tuberculosis among immigrants in a low-incidence country.immigrants from regions with a high incidence of tuberculosis (tb) are a risk group for tb in low-incidence countries such as switzerland. in a previous analysis of a nationwide collection of 520 mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat [miru-vntr] typing and spoligotyping). here, we used whole-genome sequencing (wgs) to re ...201627194683
the emergence of latent infection in the early evolution of mycobacterium tuberculosis.mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. from the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a détente with the host immune response. however, a small fraction of latent infections reactivate to the disease state. thus, latency has been argued to provide a safe harbour for future infections ...201627194699
interleukin-10 family and tuberculosis: an old story renewed.the interleukin-10 (il-10) family of cytokines consists of six immune mediators, namely il-10, il-19, il-20, il-22, il-24 and il-26. il-10, il-22, il-24 and il-26 are critical for the regulation of host defense against mycobacterium tuberculosis infections. specifically, il-10 and il-26 can suppress the antimycobacterial immunity and promote the survival of pathogen, while il-22 and il-24 can generate protective responses and inhibit the intracellular growth of pathogen. knowledge about the new ...201627194948
evaluation of the effect of pulicaria gnaphalodes and perovskia abrotanoides essential oil extracts against mycobacterium tuberculosis strains.mycobacterium tuberculosis (mtb) is the causative agent of tuberculosis (tb), which remains one of the major public health problems in the world. the increasing incidence of multidrug-resistant tuberculosis (mdr-tb) and extensively drug-resistant tuberculosis (xdr-tb) worldwide highlights the urgent need to search for alternative antimycobacterial agents. more and more people in developing countries utilize traditional medicine for their major primary health care needs. it has been determined th ...201627195252
[preclinical and clinical trials of the new tuberculosis drug perchlozon].the paper sets forth the stages of design and introduction of the new russian tuberculosis (tb) drug perchlozon registered in the russian federation in 2012. based on the results of phases i-iii clinical trials, the authors evaluate the efficacy and safety of the agent and consider the adverse effects of its treatment for respiratory tb. the use of perchlozon as a component of combination therapy versus standard chemotherapy regimens significantly reduces abacillation time in pulmonary tb caused ...201627195324
hybrid potential simulation of the acylation of enterococcus faecium l,d-transpeptidase by carbapenems.the l,d-transpeptidases, ldts, catalyze peptidoglycan cross-linking in β-lactam-resistant mutant strains of several bacteria, including enterococcus faecium and mycobacterium tuberculosis. although unrelated to the essential d,d-transpeptidases, which are inactivated by the β-lactam antibiotics, they are nevertheless inhibited by the carbapenem antibiotics, making them potentially useful targets in the treatment of some important diseases. in this work, we have investigated the acylation mechani ...201627196382
in vitro activity of copper(ii) complexes, loaded or unloaded into a nanostructured lipid system, against mycobacterium tuberculosis.tuberculosis (tb) is an infectious disease caused mainly by the bacillus mycobacterium tuberculosis (mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. the aim of this study was to evaluate a nanostructured lipid system (nls) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and eumulgin(®) hre 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer ph = 7.4) as a tactic to ...201627196901
capillary electrophoresis as a method to determine underivatized urinary lipoarabinomannans, a biomarker of active tuberculosis caused by mycobacterium tuberculosis.tuberculosis is a devastating contagious disease caused by mycobacterium tuberculosis. this is the first report describing the development of novel capillary electrophoresis methods to detect lipoarabinomannans shed into the blood circulation by replicating bacteria. the novelty of the methods is the detection without derivatization. the lipoarabinomannan is detected owing to the ionization of the diverse functional groups of the structure, such as the multibranched mannan domain or the phosphat ...201627196985
evidence of mycobacterium tuberculosis complex bacteraemia in intradermal skin test positive cattle detected using phage-rpa.bovine tuberculosis is a zoonotic infectious disease caused by mycobacterium bovis that affects cattle and can cause tuberculosis in a range of wildlife animals. a bacteriophage-based method combined with pcr (phage-pcr) has been recently used to detect and identify viable pathogenic mycobacteria in the peripheral blood mononuclear cells (pbmcs) of animals suffering from paratuberculosis. to adapt this method for the detection of m. bovis in blood, a new isothermal dna amplification protocol usi ...201627197018
functional characterization of pyrg, an unusual nonribosomal peptide synthetase module from the pyridomycin biosynthetic pathway.pyridomycin is an antimycobacterial cyclodepsipeptide assembled by a nonribosomal peptide synthetase/polyketide synthase hybrid system. analysis of its cluster revealed a nonribosomal peptide synthetase (nrps) module, pyrg, that contains two tandem adenylation domains and a pks-type ketoreductase domain. in this study, we biochemically validated that the second a domain recognizes and activates α-keto-β-methylvaleric acid (2-kvc) as the native substrate; the first a domain was not functional but ...201627197800
complete genome sequence of mycobacterium tuberculosis clinical isolate spoligotype sit745/eai1-mys.mycobacterium tuberculosis is known to cause pulmonary and extrapulmonary tuberculosis. this organism showed special phylogeographical specificity. here, we report the complete genome sequence of m. tuberculosis clinical isolate spoligotype sit745/eai1-mys, which was isolated from a malaysian tuberculosis patient.201627198011
scenario analysis for programmatic tuberculosis control in western province, papua new guinea.tuberculosis (tb) and multidrug-resistant tb (mdr-tb) are major health problems in western province, papua new guinea. while comprehensive expansion of tb control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. we parameterized our previously described mathematical model of mycobacterium tuberculosis dynamics in western province, following an epidemiologic assessment. five hypothetical scenarios representing a ...201627199387
multi-fluorescence real-time pcr assay for detection of rif and inh resistance of m. tuberculosis.failure to early detect multidrug-resistant tuberculosis (mdr-tb) results in treatment failure and poor clinical outcomes, and highlights the need to rapidly detect resistance to rifampicin (rif) and isoniazid (inh).201627199947
modular organization of the esx-5 secretion system in mycobacterium tuberculosis.mycobacteria utilize type vii secretion systems (t7ss) to export many of their important virulence proteins. the t7ss encompasses five homologous secretion systems (esx-1 to esx-5). most pathogenic mycobacterial species, including the human pathogen mycobacterium tuberculosis, possess all five esx systems. the esx-1, -3, and -5 systems are important for virulence of mycobacteria but the molecular mechanisms of their secretion apparatus and the identity and activity of secreted effector proteins ...201627200304
role of alanine dehydrogenase of mycobacterium tuberculosis during recovery from hypoxic nonreplicating persistence.mycobacterium tuberculosis can maintain a nonreplicating persistent state in the host for decades, but must maintain the ability to efficiently reactivate and produce active disease to survive and spread in a population. among the enzymes expressed during this dormancy is alanine dehydrogenase, which converts pyruvate to alanine, and glyoxylate to glycine concurrent with the oxidation of nadh to nad. it is involved in the metabolic remodeling of m. tuberculosis through its possible interactions ...201627203084
design, synthesis and biological evaluation of novel quinoline-based carboxylic hydrazides as anti-tubercular agents.in this study, seventeen novel quinoline-based carboxylic hydrazides were designed as potential anti-tubercular agents using molecular hybridization approach and evaluated in-silico for drug-likeness behavior. the compounds were synthesized, purified, and characterized using spectral techniques (like ftir, (1) h nmr, and mass). the in-vitro anti-tubercular activity (against mycobacterium tuberculosish37ra) and cytotoxicity against human lung fibroblast cells were studied. among the tested hydraz ...201627203404
working conditions and tuberculosis mortality in england and wales, 1890-1912: a retrospective analysis of routinely collected data.modelling studies suggest that workplaces may be important sites of mycobacterium tuberculosis transmission in high burden countries today. contemporary data on tuberculosis by occupation from these settings are scarce. however, historical data on tuberculosis risk in different occupations are available and may provide insight into workplace transmission. we aimed to ascertain whether, in a high burden setting, individuals working in crowded indoor environments (exposed) had greater tuberculosis ...201627207086
review on toll-like receptor activation in myasthenia gravis: application to the development of new experimental models.abnormal toll-like receptor (tlr) activation and uncontrolled resolution of inflammation are suspected to play a key role in the development of autoimmune diseases. acquired myasthenia gravis (mg) is an invalidating neuromuscular disease leading to muscle weaknesses. mg is mainly mediated by anti-acetylcholine receptor (achr) autoantibodies, and thymic hyperplasia characterized by ectopic germinal centers is a common feature in mg. an abnormal expression of certain tlrs is observed in the thymus ...201727207173
transcriptional regulation of topology modulators and transcription regulators of mycobacterium tuberculosis.mycobacterium tuberculosis (mtb) is a formidable pathogen which has the ability to survive the hostile environment of the host by evading the host defense system. the re-configuration of its transcriptional and metabolic process allows the pathogen to confront the adverse environment within the host macrophages. the factors that assist the transcription and modulate the dna topology would have to play a key role in the regulation of global gene expression of the organism. how transcription of th ...201627207833
drug-resistant tuberculosis: challenges and progress.antimicrobial resistance is a natural evolutionary process, which in the case of mycobacterium tuberculosis is based on spontaneous chromosomal mutations, meaning that well-designed combination drug regimens provided under supervised therapy will prevent the emergence of drug-resistant strains. unfortunately, limited resources, poverty, and neglect have led to the emergence of drug-resistant tuberculosis throughout the world. the international community has responded with financial and scientifi ...201627208770
endobronchial tuberculosis in anthracotic bronchitis.endobronchial tuberculosis (ebtb) is a serious form of pulmonary tuberculosis. in ebtb, mycobacterium tuberculosis involves trachea, large airways and bronchial trees combustion of biomass fuels causes anthracotic bronchitis that is characterized by black pigmentation in bronchial tissue. the majority of anthracotic bronchitis are in aged patients, particularly rural women, that use biomass fuel for cooking or traditional bakery .the aim of this study was to evaluate the endobronchial tuberculos ...201627209834
in vitro culture conditions affecting minimal inhibitory concentration of bedaquiline against m. tuberculosis.in developing a standardized drug susceptibility test for bedaquiline, it is very important to know which parameters might impact its activity in vitro and result in false resistance of the bacterium to bedaquiline. we aimed to assess the impact of different in vitro conditions on the minimal inhibitory concentration (mic) of bedaquiline against mycobacterium tuberculosis h37rv reference strain.201627210281
a long-term co-perfused disseminated tuberculosis-3d liver hollow fiber model for both drug efficacy and hepatotoxicity in babies.treatment of disseminated tuberculosis in children≤6years has not been optimized. the pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. due to hepatotoxicity worries, there are no dose-response studies in children. we designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for effic ...201627211555
development of efflux pump inhibitors in antituberculosis therapy.resistance and tolerance to antituberculosis (anti-tb) drugs, especially the first-line drugs, has become a serious problem in anti-tb therapy. efflux of antimicrobial agents via bacterial efflux pumps is one of the main reasons for drug resistance. efflux pump inhibitors (epis) bind to efflux pumps to inhibit drug efflux and thus enhance the drug effect and reduce drug resistance. studies on epis targeting the efflux pumps of mycobacterium tuberculosis (mtb) help to understand mtb resistance an ...201627211826
dry powder inhalable formulations for anti-tubercular therapy.tuberculosis (tb) is an intracellular infectious disease caused by the airborne bacterium, mycobacterium tuberculosis. despite considerable research efforts, the treatment of tb continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. the delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or v ...201627212477
rapid and simple identification of beijing genotype strain of mycobacterium tuberculosis using a loop-mediated isothermal amplification assay.beijing genotype strains of mycobacterium tuberculosis are geographically widespread and pose a notorious public health problem, these strains causing outbreaks of multidrug-resistant tuberculosis (tb); some studies have reported an association with drug resistance. because the prevalence of beijing strain has a substantial impact on tb control programs, the availability of a rapid and reliable method for detecting these strains is important for epidemiological monitoring of their circulation. t ...201627213686
tlr1 variant h305l associated with protection from pulmonary tuberculosis.toll like receptors (tlr) are key elements of the innate immune response and involved in the recognition of pathogens. to test common and rare tlr variants involved in susceptibility or resistance to infection with mycobacterium tuberculosis we screened the exons of the genes encoding tlr 1, 2, 4, and the adaptor molecule tirap in more than 4500 tuberculosis (tb) cases and controls from ghana. the analysis yielded 109 variants with possible functional impact, including 101 non-synonymous variant ...201627214039
nontoxic metal-cyclam complexes, a new class of compounds with potency against drug-resistant mycobacterium tuberculosis.tuberculosis (tb) accounted for 1.5 million deaths in 2014, and new classes of anti-tb drugs are required. we report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. these compounds inhibit intracellular growth of mycobacterium tuberculosis, are nontoxic to human cell lines, and are active against multidrug-resistant m. tuberculosis strains, indicating a distinct mode of action. these compounds warrant further ap ...201627214150
synthesis, characterization and antitubercular activities of novel pyrrolyl hydrazones and their cu-complexes.novel pyrrolyl hydrazones and their copper complexes have been synthesized and characterized using analytical and spectral techniques to show the tetrahedral geometry for cu(ii) complexes. biological activities of hydrazones have been assessed to understand the role of metal ion on their biological activity and the effect of pyrrolyl hydrazones. in vitro antitubercular activity against mycobacterium tuberculosis of the metal complexes (13b and 13r) exhibited the highest antitubercular activity t ...201627214509
investigation of elimination rate, persistent subpopulation removal, and relapse rates of mycobacterium tuberculosis by using combinations of first-line drugs in a modified cornell mouse model.currently, the most effective tuberculosis control method involves case finding and 6 months of chemotherapy. there is a need to improve our understanding about drug interactions, combination activities, and the ability to remove persistent bacteria using the current regimens, particularly in relation to relapse. we aimed to investigate the therapeutic effects of three main components, rifampin (rmp), isoniazid (inh), and pyrazinamide (pza), in current drug regimens using a modified version of t ...201627216065
perturbation of genome integrity to fight pathogenic microorganisms.resistance against antibiotics is unfortunately still a major biomedical challenge for a wide range of pathogens responsible for potentially fatal diseases.201727217086
phytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents.multi- and extensively drug-resistant tuberculosis (tb) is a global threat to human health. it requires immediate action to seek new antitubercular compounds and devise alternate strategies. nanomaterials, in the present scenario, have opened new avenues in medicine, diagnosis, and therapeutics. in view of this, the current study aims to determine the efficacy of phytogenic metal nanoparticles to inhibit mycobacteria.201627217751
lppm impact on the colonization of macrophages by mycobacterium tuberculosis.mycobacterium tuberculosis produces several bacterial effectors impacting the colonization of phagocytes. here, we report that the putative lipoprotein lppm hinders phagocytosis by macrophages in a toll-like receptor 2-dependent manner. moreover, recombinant lppm is able to functionally complement the phenotype of the mutant, when exogenously added during macrophage infection. lppm is also implicated in the phagosomal maturation, as a lppm deletion mutant is more easily addressed towards the aci ...201727220037
accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation.tuberculosis (tb), caused by mycobacterium tuberculosis (mtb) [(zopf 1883) lehmann and neumann 1896], is a major cause of morbidity and mortality. nearly one-third of the world's population is infected with mtb; tb has an annual incidence of 9 million new cases and each year causes 2 million deaths worldwide.201627220068
assembly of α-glucan by glge and glgb in mycobacteria and streptomycetes.actinomycetes, such as mycobacteria and streptomycetes, synthesize α-glucan with α-1,4 linkages and α-1,6 branching to help evade immune responses and to store carbon. α-glucan is thought to resemble glycogen except for having shorter constituent linear chains. however, the fine structure of α-glucan and how it can be defined by the maltosyl transferase glge and branching enzyme glgb were not known. using a combination of enzymolysis and mass spectrometry, we compared the properties of α-glucan ...201627221142
[spondylodiscitis in children and adolescents].spondylodiscitis in children is rare. the condition has an incidence of 2 to 4 % of all infectious skeletal diseases in children.201627221307
tuberculous arthritis of the hip with staphylococcus aureus superinfection.skeletal tuberculosis (tb) accounts for a small percentage of all cases of tb. it is often difficult to diagnose, especially in the hip joint. tb arthritis can be masked by superinfection with other pathogens, leading to a delay in diagnosis and treatment. trauma or surgery is a reported risk factor of tb arthritis. in contrast, descriptions of tb arthritis after a closed bone fracture are rare. we herein report a case involving an 81-year-old woman with septic arthritis superinfected with methi ...201627221797
deletion of nuog from the vaccine candidate mycobacterium bovis bcg δurec::hly improves protection against tuberculosis.the current tuberculosis (tb) vaccine, mycobacterium bovis bacillus calmette-guérin (bcg), provides insufficient protection against pulmonary tb. previously, we generated a listeriolysin-expressing recombinant bcg strain, which to date has successfully completed phase i and phase iia clinical trials. in an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene nuog, encoding nadh dehydrogenase 1 subunit g, from bcg δurec::hly in vitro, deletion of nuog unexpectedly led ...201627222470
chemogenomics and orthology-based design of antibiotic combination therapies.combination antibiotic therapies are being increasingly used in the clinic to enhance potency and counter drug resistance. however, the large search space of candidate drugs and dosage regimes makes the identification of effective combinations highly challenging. here, we present a computational approach called indigo, which uses chemogenomics data to predict antibiotic combinations that interact synergistically or antagonistically in inhibiting bacterial growth. indigo quantifies the influence ...201627222539
genitourinary presentation of tuberculosis.tuberculosis (tb) is less common in developed countries; however, the incidence of tb-especially resistant strains-is on the rise worldwide. cases of tb manifesting as urologic complications are rare in the united states. urologists should be aware of this potential manifestation, especially in patients who have recently immigrated to the united states or have traveled abroad for prolonged periods. two cases are presented here to illustrate this entity.201527222648
isolated posterior scleritis associated with tuberculosis.ocular tuberculosis (tb) is considered to be rare, although its incidence has varied widely over time and in different populations. latent tb is diagnosed when a person is infected with mycobacterium tuberculosis but does not have active tb. during the last decade, interferon-gamma release assay tests have been developed that allow identification of patients with latent tb infection with better specificity than the tuberculin skin test and can differentiate between infection and prior vaccinatio ...201627224075
tuberculids: cutaneous indicator diseases of mycobacterium tuberculosis infection in young patients.in the past years the incidence of tuberculosis has dropped significantly in most parts of europe and the presentation of symptomatic tuberculosis cases have become increasingly rare. with the recent influx of refugees in europe coming from tuberculosis endemic areas like the middle east and africa, it is expected that the incidence of tuberculosis will increase.201627225025
reaction mechanism of mycobacterium tuberculosis glutamine synthetase using quantum mechanics/molecular mechanics calculations.this paper is devoted to the understanding of the reaction mechanism of mycobacterium tuberculosis glutamine synthetase (mtgs) with atomic detail, using computational quantum mechanics/molecular mechanics (qm/mm) methods at the oniom m06-d3/6-311++g(2d,2p):ff99sb//b3lyp/6-31g(d):ff99sb level of theory. the complete reaction undergoes a three-step mechanism: the spontaneous transfer of phosphate from atp to glutamate upon ammonium binding (ammonium quickly loses a proton to asp54), the attack of ...201627225077
rapid drug susceptibility testing of drug-resistant mycobacterium tuberculosis isolates directly from clinical samples by use of amplicon sequencing: a proof-of-concept study.increasingly complex drug-resistant tuberculosis (dr-tb) is a major global health concern and one of the primary reasons why tb is now the leading infectious cause of death worldwide. rapid characterization of a dr-tb patient's complete drug resistance profile would facilitate individualized treatment in place of empirical treatment, improve treatment outcomes, prevent amplification of resistance, and reduce the transmission of dr-tb. the use of targeted next-generation sequencing (ngs) to obtai ...201627225403
personalized clinical diagnosis in data bases for treatment support in phthisiology.the decision-making is a key event in the clinical practice. the program products with clinical decision support models in electronic data-base as well as with fixed decision moments of the real clinical practice and treatment results are very actual instruments for improving phthisiological practice and may be useful in the severe cases caused by the resistant strains of mycobacterium tuberculosis. the methodology for gathering and structuring of useful information (critical clinical signals fo ...201627225556
the unique functional role of the c-hs hydrogen bond in the substrate specificity and enzyme catalysis of type 1 methionine aminopeptidase.it is intriguing how nature attains recognition specificity between molecular interfaces where there is no apparent scope for classical hydrogen bonding or polar interactions. methionine aminopeptidase (metap) is one such enzyme where this fascinating conundrum is at play. in this study, we demonstrate that a unique c-hs hydrogen bond exists between the enzyme methionine aminopeptidase (metap) and its n-terminal-methionine polypeptide substrate, which allows specific interaction between apparent ...201627225936
structural characterization of cyp144a1 - a cytochrome p450 enzyme expressed from alternative transcripts in mycobacterium tuberculosis.mycobacterium tuberculosis (mtb) causes the disease tuberculosis (tb). the virulent mtb h37rv strain encodes 20 cytochrome p450 (cyp) enzymes, many of which are implicated in mtb survival and pathogenicity in the human host. bioinformatics analysis revealed that cyp144a1 is retained exclusively within the mycobacterium genus, particularly in species causing human and animal disease. transcriptomic annotation revealed two possible cyp144a1 start codons, leading to expression of (i) a "full-length ...201627225995
induction of unconventional t cells by a mutant mycobacterium bovis bcg strain formulated in cationic liposomes correlates with protection against mycobacterium tuberculosis infections of immunocompromised mice.earlier studies aimed at defining protective immunity induced by mycobacterium bovis bcg immunization have largely focused on the induction of antituberculosis cd4(+) and cd8(+) t cell responses. here we describe a vaccine consisting of a bcgδmmaa4 deletion mutant formulated in dimethyl dioctadecyl-ammonium bromide (dda) with d-(+)-trehalose 6,6'-dibehenate (tdb) (dda/tdb) adjuvant (a4/adj) that protected tcrδ(-/-) mice depleted of cd4(+), cd8(+), and nk1.1(+) t cells against an aerosol challeng ...201627226281
rifampin resistance mutations are associated with broad chemical remodeling of mycobacterium tuberculosis.global control of tuberculosis has become increasingly complicated with the emergence of multidrug-resistant strains of mycobacterium tuberculosis first-line treatments are anchored by two antibiotics, rifampin and isoniazid. most rifampin resistance occurs through the acquisition of missense mutations in the rifampin resistance-determining region, an 81-base pair region encoding the rifampin binding site on the β subunit of rna polymerase (rpob). although these mutations confer a survival advan ...201627226566
posttraumatic intracranial tuberculous subdural empyema in a patient with skull fracture.intracranial tuberculous subdural empyema (itse) is extremely rare. to our knowledge, only four cases of microbiologically confirmed itse have been reported in the english literature to date. most cases have arisen in patients with pulmonary tuberculosis regardless of trauma. a 46-year-old man presented to the emergency department after a fall. on arrival, he complained of pain in his head, face, chest and left arm. he was alert and oriented. an initial neurological examination was normal. radio ...201627226867
bedaquiline and pyrazinamide treatment responses are affected by pulmonary lesion heterogeneity in mycobacterium tuberculosis infected c3heb/fej mice.balb/c and swiss mice are routinely used to validate the effectiveness of tuberculosis drug regimens, although these mouse strains fail to develop human-like pulmonary granulomas exhibiting caseous necrosis. microenvironmental conditions within human granulomas may negatively impact drug efficacy, and this may not be reflected in non-necrotizing lesions found within conventional mouse models. the c3heb/fej mouse model has been increasingly utilized as it develops hypoxic, caseous necrotic granul ...201627227164
the role of biotin in bacterial physiology and virulence: a novel antibiotic target for mycobacterium tuberculosis.biotin is an essential cofactor for enzymes present in key metabolic pathways such as fatty acid biosynthesis, replenishment of the tricarboxylic acid cycle, and amino acid metabolism. biotin is synthesized de novo in microorganisms, plants, and fungi, but this metabolic activity is absent in mammals, making biotin biosynthesis an attractive target for antibiotic discovery. in particular, biotin biosynthesis plays important metabolic roles as the sole source of biotin in all stages of the mycoba ...201627227307
exposure to mycobacterium tuberculosis during flexible bronchoscopy in patients with unexpected pulmonary tuberculosis.recent guidelines recommend the use by healthcare personnel of a fit-tested n95 particulate respirator or higher-grade respiratory precaution in a patient undergoing bronchoscopy when pulmonary tuberculosis (ptb) is suspected. however, ptb may be unexpectedly diagnosed in this setting and therefore not evaluated, resulting in the unexpected exposure to mycobacterium tuberculosis (mtb) of healthcare workers in the bronchoscopy suite. here, we examined the incidence of unexpected exposure to mtb d ...201627227408
no significant effect of asap1 gene variants on the susceptibility to tuberculosis in chinese population.recent studies have proposed that the asap1 gene participates in regulating the adaptive immune response to mycobacterium tuberculosis infection. a gwas study has reported that asap1 polymorphisms (rs4733781 and rs10956514) were associated with the risk of tuberculosis (tb) in russians. but due to population heterogeneity, different races would have different causative polymorphisms, and the aim of this study was to investigate the association between single nucleotide polymorphisms (snps) of th ...201627227929
temporal expression of peripheral blood leukocyte biomarkers in a macaca fascicularis infection model of tuberculosis; comparison with human datasets and analysis with parametric/non-parametric tools for improved diagnostic biomarker identification.a temporal study of gene expression in peripheral blood leukocytes (pbls) from a mycobacterium tuberculosis primary, pulmonary challenge model macaca fascicularis has been conducted. pbl samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified rnas hybridised to operon human genome aros v4.0 slides. data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time ...201627228113
isoniazid-induced control of mycobacterium tuberculosis by primary human cells requires interleukin-1 receptor and tumor necrosis factor.proinflammatory cytokines are critical mediators that control mycobacterium tuberculosis (mtb) growth during active tuberculosis (atb). to further inhibit bacterial proliferation in diseased individuals, drug inhibitors of cell wall synthesis such as isoniazid (inh) are employed. however, whether inh presents an indirect effect on bacterial growth by regulating host cytokines during atb is not well known. to examine this hypothesis, we used an in vitro human granuloma system generated with prima ...201627230303
high-voltage electron microscopy tomography and structome analysis of unique spiral bacteria from the deep sea.structome analysis is a useful tool for identification of unknown microorganisms that cannot be cultured. in 2012, we discovered a unique deep-sea microorganism with a cell structure intermediate between those of prokaryotes and eukaryotes and described its features using freeze-substitution electron microscopy and structome analysis (quantitative and three-dimensional structural analysis of a whole cell at the electron microscopic level). we named it myojin parakaryote here we describe, using s ...201627230559
pharmacokinetic/pharmacodynamic-based optimization of levofloxacin administration in the treatment of mdr-tb.the emergence of mdr-tb and xdr-tb has complicated tb treatment success. among many factors that contribute to the development of resistance, low drug exposure is not the least important. this review summarizes the available information on pharmacokinetic properties of levofloxacin in relation to microbial susceptibilities, in order to optimize the dose and make general treatment recommendations. a total of 37 studies on adult (32 studies) and paediatric (5 studies) mdr-tb patients were included ...201627231277
cell-envelope remodeling as a determinant of phenotypic antibacterial tolerance in mycobacterium tuberculosis.the mechanisms that lead to phenotypic antibacterial tolerance in bacteria remain poorly understood. we investigate whether changes in nacl concentration toward physiologically higher values affect antibacterial efficacy against mycobacterium tuberculosis (mtb), the causal agent of human tuberculosis. indeed, multiclass phenotypic antibacterial tolerance is observed during mtb growth in physiologic saline. this includes changes in sensitivity to ethionamide, ethambutol, d-cycloserine, several am ...201627231718
the fbpase encoding gene glpx is required for gluconeogenesis, bacterial proliferation and division in vivo of mycobacterium marinum.lipids have been identified as important carbon sources for mycobacterium tuberculosis (mtb) to utilize in vivo. thus gluconeogenesis bears a key role for mtb to survive and replicate in host. a rate-limiting enzyme of gluconeogenesis, fructose 1, 6-bisphosphatase (fbpase) is encoded by the gene glpx. the functions of glpx were studied in m. marinum, a closely related species to mtb. the glpx deletion strain (δglpx) displayed altered gluconeogenesis, attenuated virulence, and altered bacterial p ...201627233038
human xenobiotic nuclear receptor pxr augments mycobacterium tuberculosis survival.mycobacterium tuberculosis can evade host defense processes, thereby ensuring its survival and pathogenesis. in this study, we investigated the role of nuclear receptor, pregnane x receptor (pxr), in m. tuberculosis infection in human monocyte-derived macrophages. in this study, we demonstrate that pxr augments m. tuberculosis survival inside the host macrophages by promoting the foamy macrophage formation and abrogating phagolysosomal fusion, inflammation, and apoptosis. additionally, m. tuberc ...201627233963
the type of growth medium affects the presence of a mycobacterial capsule and is associated with differences in protective efficacy of bcg vaccination against mycobacterium tuberculosis.bacillus calmette-guerin (bcg) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. most immunological studies of bcg or mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. the impact of the capsule on vaccine efficacy has not been explored.201627234419
description of compensatory gyra mutations restoring fluoroquinolone susceptibility in mycobacterium tuberculosis.resistance to fluoroquinolones (fqs) in mycobacterium tuberculosis (mtb) is mainly due to mutations in dna gyrase (gyra2b2), with the most common substitutions located at positions 90 and 94 in gyra. two clinical mdr mtb (mdr-tb) strains harbouring an a90e or d94n substitution in gyra were found to be surprisingly susceptible to fqs (ofloxacin mic ≤2 mg/l). we studied the impact of the additional gyra substitutions found in these strains (t80a and t80a + a90g, respectively) on fq susceptibility.201627234461
antimicrobial peptides as novel anti-tuberculosis therapeutics.tuberculosis (tb), a disease caused by the human pathogen mycobacterium tuberculosis, has recently joined hiv/aids as the world's deadliest infectious disease, affecting around 9.6 million people worldwide in 2014. of those, about 1.2 million died from the disease. resistance acquisition to existing antibiotics, with the subsequent emergence of multi-drug resistant mycobacteria strains, together with an increasing economic burden, has urged the development of new anti-tb drugs. in this scope, an ...201627235189
distal hydrogen-bonding interactions in ligand sensing and signaling by mycobacterium tuberculosis doss.mycobacterium tuberculosis doss is critical for the induction of m. tuberculosis dormancy genes in response to nitric oxide (no), carbon monoxide (co), or hypoxia. these environmental stimuli, which are sensed by the doss heme group, result in autophosphorylation of a doss his residue, followed by phosphotransfer to an asp residue of the response regulator dosr. to clarify the mechanism of gaseous ligand recognition and signaling, we investigated the hydrogen-bonding interactions of the iron-bou ...201627235395
hematemesis: unusual presentation of isolated gastric tuberculosis.a 25-year-old male presented with hematemesis, epigastric pain, and melena. he had dyspepsia with significant weight loss for 3 months period. on clinical examination, he was pale with no organomegaly or lymphadenopathy. the x-ray chest was normal, and ultrasound abdomen was normal. upper gi endoscopy revealed nodularity and ulceration along proximal part of lesser curvature of the stomach. ct scan abdomen showed thickening of lesser curvature just below gastro-esophageal junction. the biopsies ...201627235948
anti-mycobacterial activity of thymine derivatives bearing boron clusters.a series of novel thymine derivatives bearing lipophilic, electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane or hydrophilic 7,8-dicarba-nido-undecaborate anions were synthesized. synthesis was performed via copper(i)-catalysed huisgen-meldal-sharpless 1,3-dipolar cycloaddition of n(1)-propargylthymine or n(1),n(3)-bispropargylthymine to 1-(3-azidopropyl)-1,2-dicarba-closo-dodecaborane. the obtained compounds were tested in vitro against mycobacterium tuberculosis th ...201627236064
[methods for determining the antimicrobial susceptibility of mycobacteria].mycobacteria are a large group of microorganisms, multiple species of which are major causes of morbidity and mortality, such as tuberculosis and leprosy. at present, the emergence and spread of multidrug-resistant strains of mycobacterium tuberculosis complex are one of the most serious health problems worldwide. furthermore, in contrast to m. tuberculosis and mycobacterium leprae, non-tuberculous mycobacteria (ntm) are more frequently isolated and, in many cases, treatment is based on drug sus ...201627236235
spatially explicit modeling of animal tuberculosis at the wildlife-livestock interface in ciudad real province, spain.eurasian wild boar (sus scrofa) and red deer (cervus elaphus) are the most important wildlife reservoirs for animal tuberculosis (tb) caused by the mycobacterium tuberculosis complex (mtc), in mediterranean spain. these species are considered to play an important role in the transmission and persistence of mtc in cattle in some regions; however the factors contributing to the risk of transmission at the wildlife-livestock interface and the areas at highest risk for such transmission are largely ...201627237396
tuberculous gastric abscess in a patient with aids: a rare presentation.tuberculosis is a healthcare concern that affects millions of individuals around the globe. coinfection with hiv has changed both the clinical presentation and the outcome of the disease dramatically in the last few decades. extrapulmonary tuberculosis is seen more frequently in the immunocompromised host. an unusual case of gastric tuberculosis in an aids patient is reported here. a 49-year-old female with aids was admitted for fever and epigastric pain. a gastric submucosal abscess was observe ...201627239353
discovery of in vitro antitubercular agents through in silico ligand-based approaches.the development of new anti-tubercular agents represents a constant challenge mostly due to the insurgency of resistance to the currently available drugs. in this study, a set of 60 molecules were selected by screening the asinex and the zinc collections and an in house library by means of in silico ligand-based approaches. biological assays in mycobacterium tuberculosis h37ra atcc 25177 strain highlighted (±)-1-(4-chlorophenyl)-2-(1h-imidazol-1-yl)ethyl-4-(3,4-dichlorophenyl)piperazine-1-carbox ...201627240272
total synthesis of cyclomarins a, c and d, marine cyclic peptides with interesting anti-tuberculosis and anti-malaria activities.cyclomarins are cyclic heptapeptides containing four unusual amino acids. new synthetic protocols toward their synthesis have been developed, leading to the synthesis and biological evaluation of three natural occurring cyclomarins. interestingly, cyclomarins address two completely different targets: clp c1, a subunit of the caseinolytic protease of mycobacterium tuberculosis (mtb), as well as pfap3ase of plasmodium falciparum. therefore, cyclomarins are interesting lead structures for the devel ...201627241518
identification of mycobacterium tuberculosis leucyl-trna synthetase (leurs) inhibitors among the derivatives of 5-phenylamino-2h-[1,2,4]triazin-3-one.the increase of antibiotic resistance amongst mycobacterium tuberculosis strains has become one of the most pressing problems of modern medicine. therefore, the search of antibiotics against m. tuberculosis with novel mechanisms of action is very important. we have identified inhibitors of m. tuberculosis leucyl-trna synthetase (leurs) among the derivatives of 5-phenylamino-2h-[1,2,4]triazin-3-one. the most active compounds 5-(5-chloro-2-hydroxy-phenylamino)-6-methyl-2h-[1,2,4]triazin-3-one and ...201627241561
a study on pre-xdr & xdr tuberculosis & their prevalent genotypes in clinical isolates of mycobacterium tuberculosis in north india.pre-extensively drug resistant (pre-xdr) and extensively drug resistant tuberculosis (xdr-tb) have been areas of growing concern, and are posing threat to global efforts of tb control. the present study was planned to study the presence of pre-xdr and xdr mycobacterium tuberculosis and their genotypes in clinical isolates obtained from previously treated cases of pulmonary tb.201627241648
antimycobacterial activity of new n(1)-[1-[1-aryl-3-[4-(1h-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives.n(1)-[1-[1-aryl-3-[4-(1h-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives were design, synthesized and tested for their in vitro antimycobacterial activity. the new compounds showed a moderate antimycobacterial activity against the tested strain of mycobacterium tuberculosis h37ra and a significant antimycobacterial activity against several mycobacteria other than tuberculosis strains.201627241693
comparison of two molecular assays for detecting smear negative pulmonary tuberculosis.to compare the performance of mtbdrplus v2 and xpert mtb/rif for detecting smear negative pulmonary tuberculosis (ptb).201627241735
selection of phage-displayed human antibody fragments specific for cd1b presenting the mycobacterium tuberculosis glycolipid ac2sgl.the development of new tools capable of targeting mycobacterium tuberculosis (mtb)-infected cells have potential applications in diagnosis, treatment, and prevention of tuberculosis. in mtb-infected cells, cd1b molecules present mtb lipids to the immune system (mtb lipid-cd1b complexes). because of the lack of cd1b polymorphism, specific mtb lipid-cd1b complexes could be considered as universal mtb infection markers. 2-stearoyl-3-hydroxyphthioceranoyl-2'-sulfate-α-α'-d-trehalose (ac2sgl) is spec ...201627242221
genotyping of mutations detected with genexpert.tuberculosis remains an important cause of mortality worldwide. previous tuberculosis treatment is a strong determinant of multi-drug resistant tuberculosis. the study objective was to describe the mutations detected of mycobacterium tuberculosis (mtb) complex clinical strains screened with genexpert isolated from previously treated patients in côte d'ivoire.201627242224
use of rodac plates to measure containment of mycobacterium tuberculosis in a class iib biosafety cabinet during routine operations.guidelines for the manipulation of mycobacterium tuberculosis (mtb) cultures require a biosafety level 3 (bsl-3) infrastructure and accompanying code of conduct. in this study, we aimed to validate and apply detection methods for viable mycobacteria from surfaces in a bsl-3 mtb laboratory.201627242225
the pros and cons of the quantiferon test for the diagnosis of tuberculosis, prediction of disease progression, and treatment monitoring.tuberculosis (tb) is a re-emerging disease with the advent of human immunodeficiency virus/aids infections. discovered in 1959, diagnosed by various approaches and treated with antibiotics, the treatment of tb infection still poses public health concerns. many cases of resistance and cross-resistance are observed. diagnosis by culture, which is considered as the standard method, takes too long (20-30days) and is not suitable for extrapulmonary tb. quantiferon test, which is an indirect immunoass ...201627242229
drug resistance-conferring mutations in mycobacterium tuberculosis from pulmonary tuberculosis patients in southwest ethiopia.the nature and frequency of mutations in rifampicin (rif) and isoniazid (inh) resistant mycobacterium tuberculosis isolates vary considerably according to geographic locations. however, information regarding specific mutational patterns in ethiopia remains limited.201627242230
limonia acidissima l. leaf mediated synthesis of zinc oxide nanoparticles: a potent tool against mycobacterium tuberculosis.the present investigation was undertaken to synthesize zinc oxide nanoparticles using limonia acidissima l. and to test their efficacy against the growth of mycobacterium tuberculosis.201627242232
chronic oozing skin lesions in children: possible tuberculosis? two case reports.cutaneous tuberculosis is frequently misleading and challenging, as it mimics a wide differential diagnosis. here, we present two pediatric cases with chronic multiple ulcerating nodules. proper history, physical examination, and histopathological analysis are included in the workup of suspected skin tuberculosis. diagnosis was confirmed by positive culture for mycobacteria.201627242235
high prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using genexpert mycobacterium tuberculosis/rifampicin in ghana.drug-resistant strains of tuberculosis (tb) represent a major threat to global tb control. in low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. molecular assays such as the genexpert mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. the objective of this study is to evaluate the use of genexpert in the diagnosis of pulm ...201627242237
tuberculous ventriculitis: a rare complication of central nervous system tuberculosis.tuberculous ventriculitis is an inflammatory infection of the ventricular system of the brain, and is caused by mycobacterium tuberculosis. we herein present the case of an immunocompromised patient with brain tuberculomas who developed ventriculitis during treatment. the patient was successfully treated with a high dose of steroid, long-term antituberculosis drugs, and aggressive supportive care.201627242238
mathematical models of tuberculosis reactivation and relapse.the natural history of human infection with mycobacterium tuberculosis (mtb) is highly variable, as is the response to treatment of active tuberculosis. there is presently no direct means to identify individuals in whom mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. the 3 models discussed in this review i ...201627242697
phosphorylation modulates catalytic activity of mycobacterial sirtuins.sirtuins are nad(+)-dependent deacetylases involved in the regulation of diverse cellular processes and are conserved throughout phylogeny. here we report about in vitro transphosphorylation of the only nad(+)-dependent deacetylase (mdac) present in the genome of mycobacterium tuberculosis by eukaryotic-type ser/thr kinases, particularly pkna. the phosphorylated mdac displayed decreased deacetylase activity compared to its unphosphorylated counterpart. mass-spectrometric study identified seven p ...201627242704
mycobacterium tuberculosis co-operonic pe32/ppe65 proteins alter host immune responses by hampering th1 response.pe/ppe genes, present in cluster with esat-6 like genes, are suspected to have a role in antigenic variation and virulence of mycobacterium tuberculosis. their roles in immune evasion and immune modulation of host are also well documented. we present evidence that pe32/ppe65 present within the rd8 region are co-operonic, co-transcribed, and co-translated, and play role in modulating host immune responses. experiments with macrophage cell lines revealed that this protein complex suppresses pro-in ...201627242739
polyphosphate kinase mediates antibiotic tolerance in extraintestinal pathogenic escherichia coli pcn033.extraintestinal pathogenic escherichia coli (expec) causes a variety of acute infections in its hosts, and multidrug-resistant strains present significant challenges to public health and animal husbandry. therefore, it is necessary to explore new drug targets to control e. coli epidemics. previous studies have reported that ppk mutants of burkholderia pseudomallei and mycobacterium tuberculosis are more susceptible than the wild types (wts) to stress. therefore, we investigated the stress respon ...201627242742
the zebrafish breathes new life into the study of tuberculosis.tuberculosis (tb) is a global health emergency. up to one-third of the world's population is infected with mycobacterium tuberculosis, and the pathogen continues to kill 1.5 million people annually. currently, the means for preventing, diagnosing, and treating tb are unsatisfactory. one of the main reasons for the poor progress in tb research has been a lack of good animal models to study the latency, dormancy, and reactivation of the disease. although sophisticated in vitro and in silico method ...201627242801
autophagy-related proteins target ubiquitin-free mycobacterial compartment to promote killing in macrophages.autophagy is a lysosomal degradative process that plays essential functions in innate immunity, particularly, in the clearance of intracellular bacteria such as mycobacterium tuberculosis. the molecular mechanisms involved in autophagy activation and targeting of mycobacteria, in innate immune responses of macrophages, are only partially characterized. autophagy targets pathogenic m. tuberculosis via a cytosolic dna recognition- and an ubiquitin-dependent pathway. in this report, we show that no ...201627242971
three months of weekly rifapentine and isoniazid for treatment of mycobacterium tuberculosis infection in hiv-coinfected persons.compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3hp) versus 9 months of daily isoniazid (9h) in hiv-infected persons.201627243774
cd4 t cell-derived ifn-γ plays a minimal role in control of pulmonary mycobacterium tuberculosis infection and must be actively repressed by pd-1 to prevent lethal disease.ifn-γ-producing cd4 t cells are required for protection against mycobacterium tuberculosis (mtb) infection, but the extent to which ifn-γ contributes to overall cd4 t cell-mediated protection remains unclear. furthermore, it is not known if increasing ifn-γ production by cd4 t cells is desirable in mtb infection. here we show that ifn-γ accounts for only ~30% of cd4 t cell-dependent cumulative bacterial control in the lungs over the first six weeks of infection, but >80% of control in the spleen ...201627244558
a mutation in the 16s rrna decoding region attenuates the virulence of mycobacterium tuberculosis.mycobacterium tuberculosis contains a single rrna operon that encodes targets for antituberculosis agents, including kanamycin. to date, only four mutations in the kanamycin binding sites of 16s rrna have been reported in kanamycin-resistant clinical isolates. we hypothesized that another mutation(s) in the region may dramatically decrease m. tuberculosis viability and virulence. here, we describe an rrna mutation, u1406a, which was generated in vitro and confers resistance to kanamycin while hi ...201627245411
role of metal-dependent regulation of esx-3 secretion in intracellular survival of mycobacterium tuberculosis.more people die every year from mycobacterium tuberculosis infection than from infection by any other bacterial pathogen. type vii secretion systems (t7ss) are used by both environmental and pathogenic mycobacteria to secrete proteins across their complex cell envelope. in the nonpathogen mycobacterium smegmatis, the esx-1 t7ss plays a role in conjugation, and the esx-3 t7ss is involved in metal homeostasis. in m. tuberculosis, these secretion systems have taken on roles in virulence, and they a ...201627245412
hypoxia and tissue destruction in pulmonary tb.it is unknown whether lesions in human tb are hypoxic or whether this influences disease pathology. human tb is characterised by extensive lung destruction driven by host matrix metalloproteinases (mmps), particularly collagenases such as matrix metalloproteinase-1 (mmp-1).201627245780
activity of phosphino palladium(ii) and platinum(ii) complexes against hiv-1 and mycobacterium tuberculosis.treatment of human immunodeficiency virus (hiv) is currently complicated by increased prevalence of co-infection with mycobacterium tuberculosis. the development of drug candidates that offer the simultaneous management of hiv and tuberculosis (tb) would be of great benefit in the holistic treatment of hiv/aids, especially in sub-saharan africa which has the highest global prevalence of hiv-tb coinfection. bis(diphenylphosphino)-2-pyridylpalladium(ii) chloride (1), bis(diphenylphosphino)-2-pyrid ...201627246555
animal-adapted members of the mycobacterium tuberculosis complex endemic to the southern african subregion.members of the mycobacterium tuberculosis complex (mtc) cause tuberculosis (tb) in both animals and humans. in this article, three animal-adapted mtc strains that are endemic to the southern african subregion - that is, mycobacterium suricattae, mycobacterium mungi, and the dassie bacillus - are reviewed with a focus on clinical and pathological presentations, geographic distribution, genotyping methods, diagnostic tools and evolution. moreover, factors influencing the transmission and establish ...201627246904
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