| syndecan-1 and heparanase: potential markers for activity evaluation and differential diagnosis of crohn's disease. | syndecan-1 (sdc1) and its endo-beta-d-glucuronidase heparanase (hpa) are implicated in the maintenance of intestinal barrier function, but their detailed functions in crohn's disease (cd) are not fully investigated. the aim of this study was to determine alteration patterns of sdc1 and hpa and their potential roles in evaluating disease activity and differentiating cd from intestinal tuberculosis (itb). | 2013 | 23511033 |
| resisting resistant mycobacterium tuberculosis naturally: mechanistic insights into the inhibition of the parasite's sole signal peptidase leader peptidase b. | tuberculosis (tb) is the second highest cause of mortality after hiv/aids and is one of the leading public health problems worldwide. the growing resistance to anti-tb drugs and the recalcitrant nature of tenacious infections present arduous challenges for the treatment of tb. thus, the need to develop therapeutics against novel drug targets to help overcome multi-drug resistant tb is inevitable. leader peptidase b (lepb), the sole signal peptidase of mycobacterium tuberculosis (mtb), is one suc ... | 2013 | 23510997 |
| esophageal perforation caused by mycobacterium tuberculosis. | | 2013 | 23510946 |
| characteristics and outcomes of tuberculosis patients who fail to smear convert at two months in sri lanka. | five districts in sri lanka. | 2013 | 26392992 |
| triterpenes and the antimycobacterial activity of duroia macrophylla huber (rubiaceae). | duroia macrophylla popularly known as "cabeça-de-urubú," "apuruí," or "puruí-grande-da-mata" occurs in the amazon forest. its leaves and branches were collected twice and extracted with dichloromethane and methanol. all extracts were subjected to phytochemical investigation and terpenes and flavonoids were found in all dichloromethane and methanol extracts, respectively. methanol extracts from both branches (1st collection) and leaves (2nd collection) presented hydrolyzed tannins, yet alkaloids ... | 2013 | 23509750 |
| changing patterns and trends of multidrug-resistant tuberculosis at referral centre in northern india: a 4-year experience. | india has a high burden of drug-resistant tuberculosis (tb), although there is little data on multidrug-resistant tuberculosis (mdr-tb). although mdr-tb has existed for long time in india, very few diagnostic laboratories are well-equipped to test drug sensitivity. the objectives of this study were to determine the prevalence of mdr-tb, first-line drug resistance patterns and its changing trends in northern india in the 4 years. | 2013 | 23508428 |
| multiplex polymerase chain reaction using insertion sequence 6110 (is6110) and mycobacterial protein fraction from bcg of rm 0.64 in electrophoresis target genes for diagnosis of tuberculous lymphadenitis. | tubercular lymphadenitis (tbla) is a common manifestations of extrapulmonary tuberculosis (eptb) accounting for 30-40% of cases. prompt diagnosis and timely initiation of anti-tubercular therapy (att) is the key for successful clinical outcome. this study was carried out to evaluate multiplex polymerase chain reaction (mpcr) using mpb64 and is6110, and compare with the conventional methods for rapid diagnosis of tbla. | 2013 | 23508425 |
| susceptibility to mycobacterium tuberculosis infection in hiv-positive patients is associated with card8 genetic variant. | hla and other genetic variants, playing an important role in innate and adaptive immunity, are known to influence tuberculosis (tb) development in hiv-1-positive (hiv+) patients. because inflammasome genes contribute to hiv-1 susceptibility, we investigated the possible association between polymorphisms in inflammasome genes with hiv-1 and mycobacterium tuberculosis coinfection (hiv+tb+) in a case/control cohort of brazilian individuals. nineteen single-nucleotide polymoprhims in 8 inflammasome ... | 2013 | 23507658 |
| in vitro and in vivo efficacy of β-lactams against replicating and slowly growing/nonreplicating mycobacterium tuberculosis. | beta-lactams, in combination with beta-lactamase inhibitors, are reported to have activity against mycobacterium tuberculosis bacteria growing in broth, as well as inside the human macrophage. we tested representative beta-lactams belonging to 3 different classes for activity against replicating m. tuberculosis in broth and nonreplicating m. tuberculosis under hypoxia, as well as against streptomycin-starved m. tuberculosis strain 18b (ss18b) in the presence or absence of clavulanate. most of th ... | 2013 | 23507276 |
| efficacy of nitazoxanide against clinical isolates of mycobacterium tuberculosis. | nitazoxanide (ntz) has bactericidal activity against the h37rv laboratory strain of mycobacterium tuberculosis with a mic of 16 μg/ml. however, its efficacy against clinical isolates of m. tuberculosis has not been determined. we found that ntz's mic against 50 clinical isolates ranged from 12 to 28 μg/ml with a median of 16 μg/ml and was unaffected by resistance to first- or second-line antituberculosis drugs or a diversity of spoligotypes. | 2013 | 23507275 |
| field evaluation of the direct detection of multidrug resistant mycobacterium tuberculosis by nitrate reductase assay on 7h11 agar. | in this study we evaluated the performance of colorimetric nitrate reductase assay (nra) on middlebrook 7h11 agar instead of lowenstein-jensen medium for detection of isoniazid (inh) and rifampin (rif) resistance directly on 114 smear positive sputum specimens and compared the results with direct proportion method on lj medium. the results of both methods were in 100% agreement for detection of rif resistance while agreement for inh was 96.4%. the average turnaround time for nra was 18.6 days an ... | 2013 | 23507185 |
| isocitrate lyase: a potential target for anti-tubercular drugs. | current tb regimen involves a combination of first and second line drugs which target only a small number of core metabolic processes such as deoxyribonucleic acid (dna)/ ribonucleic acid (rna) synthesis, cell wall synthesis, and energy metabolism pathways. new classes of drugs with additional drug targets that are resistant to mutation are an urgent necessity. novel targets involved in vital aspects of bacterial growth, metabolism and viability and whose inactivation would lead to bacterial dea ... | 2013 | 23506018 |
| stroke in a patient with tuberculous meningitis and hiv infection. | tuberculous meningitis (tbm) is a devastating disease. tbm occurs more commonly in hiv infected patients. the influence of hiv co-infection on clinical manifestations and outcome of tbm is not well defined. yet, some differences have been observed and stroke has been recorded to occur more frequently. this study reports on an hiv infected caucasian female with lung, meningeal tuberculosis and stroke due to a cortical sub-cortical ischemic lesion. tbm was documented in the absence of neurologic s ... | 2013 | 23505605 |
| hiv infection disrupts the sympatric host-pathogen relationship in human tuberculosis. | the phylogeographic population structure of mycobacterium tuberculosis suggests local adaptation to sympatric human populations. we hypothesized that hiv infection, which induces immunodeficiency, will alter the sympatric relationship between m. tuberculosis and its human host. to test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of hiv-infected and hiv-negative patients with tuberculosis (tb) between 2000 and 2008 in switzerland. we analyzed 518 tb patie ... | 2013 | 23505379 |
| substrate specificity of marp, a periplasmic protease required for resistance to acid and oxidative stress in mycobacterium tuberculosis. | the transmembrane serine protease marp is important for ph homeostasis in mycobacterium tuberculosis (mtb). previous structural studies revealed that marp contains a chymotrypsin fold and a disulfide bond that stabilizes the protease active site in the substrate-bound conformation. here, we determined that marp is located in the mtb periplasm and showed that this localization is essential for function. using the recombinant protease domain of marp, we identified its substrate specificity using t ... | 2013 | 23504313 |
| [diagnosis of pulmonary tuberculosis using ziehl-neelsen stain and polymerase chain reaction]. | definitive diagnosis of unclear pulmonary lesions is mainly based on morphological methods. in addition to a neoplasm, inflammatory reactions, in particular tuberculosis (tb), have to be considered in most cases. therefore, the aim of this work was to determine whether established methods used in general pathology can be efficiently used with cytological material. | 2013 | 23503854 |
| impact of the antiretroviral treatment program on the burden of hospitalization for culture-confirmed tuberculosis in south african children: a time-series analysis. | the hiv epidemic increased the burden of tuberculosis (tb) in sub-saharan africa. we evaluated the impact that scaling-up of the public-funded antiretroviral treatment (art) program had on incidence of hospitalization for culture-confirmed and overall-tb in hiv-infected and hiv-uninfected children from 2005 to 2009. | 2013 | 23503163 |
| allopatric tuberculosis host-pathogen relationships are associated with greater pulmonary impairment. | host pathogen relationships can be classified as allopatric, when the pathogens originated from separate, non-overlapping geographic areas from the host; or sympatric, when host and pathogen shared a common ancestral geographic location. it remains unclear if host-pathogen relationships, as defined by phylogenetic lineage, influence clinical outcome. we sought to examine the association between allopatric and sympatric phylogenetic mycobacterium tuberculosis lineages and pulmonary impairment aft ... | 2013 | 23501297 |
| the canadian medicinal plant heracleum maximum contains antimycobacterial diynes and furanocoumarins. | heracleum maximum is amongst the most commonly used plants by the indigenous peoples of north america. the first nations of the eastern canada use infusions of heracleum maximum roots for the treatment of respiratory ailments including tuberculosis. previous investigations of extracts derived from the roots of heracleum maximum have shown it to possess antimycobacterial activity. | 2013 | 23501157 |
| amino-acid substitutions at the domain interface affect substrate and allosteric inhibitor binding in α-isopropylmalate synthase from mycobacterium tuberculosis. | α-isopropylmalate synthase (α-ipms) is a multi-domain protein catalysing the condensation of α-ketoisovalerate (α-kiv) and acetyl coenzyme a (accoa) to form α-isopropylmalate. this reaction is the first committed step in the leucine biosynthetic pathway in bacteria and plants, and α-ipms is allosterically regulated by this amino acid. existing crystal structures of α-ipms from mycobacterium tuberculosis (mtuipms) indicate that this enzyme has a strikingly different domain arrangement in each mon ... | 2013 | 23500460 |
| genetic features shared by mycobacterium tuberculosis strains involved in microevolution events. | microevolved mycobacterium tuberculosis (mtb) clonal variants from a parental strain can emerge within a single patient infection and during transmission events. genotypic rearrangements may involve functional changes conferring advantages to favor strain adaptation to the host. in the present study, we analyzed in depth some genotypic characteristics of a strain with a high tendency to microevolve that generated 6 clonal variants during transmission of sequential hosts. in order to identify gen ... | 2013 | 23499710 |
| assessment of potential causes of falsely positive mycobacterium tuberculosis breath test. | a suite of volatiles have previously been identified as specific markers of mycobacterium tuberculosis metabolism in vitro. these markers - methyl phenylacetate, methyl p-anisate, methyl nicotinate, o-phenylanisole with the addition of methyl salicylate, may also be derived from other sources and confound development of a breath test for tuberculosis. to identify potential sources of these potential biomarkers food products, cosmetics, tb medication, environmental air and cigarette smoke were an ... | 2013 | 23499413 |
| antibody-mediated immunity against tuberculosis: implications for vaccine development. | there is an urgent need for new and better vaccines against tuberculosis (tb). current vaccine design strategies are generally focused on the enhancement of cell-mediated immunity. antibody-based approaches are not being considered, mostly due to the paradigm that humoral immunity plays little role in the protection against intracellular pathogens. here, we reappraise and update the increasing evidence for antibody-mediated immunity against mycobacterium tuberculosis, discuss the complexity of a ... | 2013 | 23498951 |
| tb mobile: a mobile app for anti-tuberculosis molecules with known targets. | an increasing number of researchers are focused on strategies for developing inhibitors of mycobacterium tuberculosis (mtb) as tuberculosis (tb) drugs. | 2013 | 23497706 |
| designing of inhibitors against drug tolerant mycobacterium tuberculosis (h37rv). | mycobacterium tuberculosis (m.tb) is the causative agent of tuberculosis, killing ~1.7 million people annually. the remarkable capacity of this pathogen to escape the host immune system for decades and then to cause active tuberculosis disease, makes m.tb a successful pathogen. currently available anti-mycobacterial therapy has poor compliance due to requirement of prolonged treatment resulting in accelerated emergence of drug resistant strains. hence, there is an urgent need to identify new che ... | 2013 | 23497593 |
| health workers' performance in the implementation of patient centred tuberculosis treatment (pct) strategy under programmatic conditions in tanzania: a cross sectional study. | patient centred tuberculosis treatment (pct) is a promising treatment delivery strategy for mycobacterium tuberculosis (tb). it aims to improve adherence to treatment by giving patients the choice of having drug intake supervised at the health facility by a medical professional or at home by a supporter of their choice. | 2013 | 23497025 |
| molecular epidemiology and transmission dynamics of mycobacterium tuberculosis in northwest ethiopia: new phylogenetic lineages found in northwest ethiopia. | although ethiopia ranks seventh among the world's 22 high-burden tuberculosis (tb) countries, little is known about strain diversity and transmission. in this study, we present the first in-depth analysis of the population structure and transmission dynamics of mycobacterium tuberculosis strains from northwest ethiopia. | 2013 | 23496968 |
| the mutation rate of mycobacterial repetitive unit loci in strains of m. tuberculosis from cynomolgus macaque infection. | mycobacterial interspersed repetitive units (mirus) are minisatellites within the mycobacterium tuberculosis (mtb) genome. copy number variation (cnv) in miru loci is used for epidemiological typing, making the rate of variation important for tracking the transmission of mtb strains. in this study, we developed and assessed a whole-genome sequencing (wgs) approach to detect miru cnv in mtb. we applied this methodology to a panel of mtb strains isolated from the macaque model of tuberculosis (tb) ... | 2013 | 23496945 |
| structure of mycobacterial β-oxidation trifunctional enzyme reveals its altered assembly and putative substrate channeling pathway. | the incidence of tuberculosis is increasing due to the appearance of new drug-resistant variants. a thorough understanding of the disease organism is essential in order to create more effective drugs. in an attempt to understand better the poorly studied lipid metabolism of mycobacterium tuberculosis (mtb), we identified and characterized its fatty acid β-oxidation complex (trifunctional enzyme (tfe)). tfe is an α(2)β(2) complex consisting of two types of polypeptides catalyzing three of the fou ... | 2013 | 23496842 |
| advances in the diagnosis and treatment of tuberculous meningitis. | early diagnosis and treatment of tuberculous meningitis (tbm) saves lives, but current laboratory diagnostic tests lack sensitivity and the best treatment regimens are uncertain. this article reviews the advances towards better tbm diagnosis and treatments made over the last 2 years. | 2013 | 23493162 |
| characterization of multiple and extensively drug resistant mycobacterium tuberculosis isolates with different ofloxacin-resistance levels. | the goal of the study was to determine different mutation types in gyra and gyrb genes in mycobacterium tuberculosis strains with low-level (2 μg/ml) and high-level (10 μg/ml) ofloxacin (ofl) resistance and to compare genetic diversity of ofloxacin-resistant and susceptible m. tuberculosis isolates. m. tuberculosis isolates were collected in leningrad region in 2011. dna sequencing showed that 54.3% of isolates with low-level and 76.9% of isolates with high-level ofl-resistance had mutations in ... | 2013 | 23491718 |
| il12b expression is sustained by a heterogenous population of myeloid lineages during tuberculosis. | il12b is required for resistance to mycobacterium tuberculosis (mtb) infection, promoting the initiation and maintenance of mtb-specific effector responses. while this makes the il12-pathway an attractive target for experimental tuberculosis (tb) therapies, data regarding what lineages express il12b after infection is established are limited. this is not obvious in the lung, an organ in which both hematopoietic and non-hematopoietic lineages produce il12p40 upon pathogen encounter. here, we use ... | 2013 | 23491716 |
| il-1β promotes antimicrobial immunity in macrophages by regulating tnfr signaling and caspase-3 activation. | in vivo control of mycobacterium tuberculosis reflects the balance between host immunity and bacterial evasion strategies. effector th1 cells that mediate protective immunity by depriving the bacterium of its intracellular niche are regulated to prevent overexuberant inflammation. one key immunoregulatory molecule is tim3. although tim3 is generally recognized to downregulate th1 responses, we recently described that its interaction with galectin-9 expressed by m. tuberculosis-infected macrophag ... | 2013 | 23487424 |
| a meta-analysis of self-administered vs directly observed therapy effect on microbiologic failure, relapse, and acquired drug resistance in tuberculosis patients. | preclinical studies and monte carlo simulations have suggested that there is a relatively limited role of adherence in acquired drug resistance (adr) and that very high levels of nonadherence are needed for therapy failure. we evaluated the superiority of directly observed therapy (dot) for tuberculosis patients vs self-administered therapy (sat) in decreasing adr, microbiologic failure, and relapse in meta-analyses. | 2013 | 23487389 |
| clinical effects of gemifloxacin on the delay of tuberculosis treatment. | although gemifloxacin has low in vitro activity against mycobacterium tuberculosis, the effect of gemifloxacin on the delay of tuberculosis (tb) treatment has not been validated in a clinical setting. the study group included patients with culture-confirmed pulmonary tb who initially received gemifloxacin for suspected community-acquired pneumonia (cap). two control groups contained patients treated with other fluoroquinolones or nonfluoroquinolone antibiotics. sixteen cases were treated with ge ... | 2013 | 23486643 |
| activation of atp binding for the autophosphorylation of doss, a mycobacterium tuberculosis histidine kinase lacking an atp lid motif. | the sensor histidine kinases of mycobacterium tuberculosis, doss and dost, are responsible for sensing hypoxic conditions and consist of sensor and kinase cores responsible for accepting signals and phosphorylation activity, respectively. the kinase core contains a dimerization and histidine phosphate-accepting (dhp) domain and an atp binding domain (abd). the 13 histidine kinase genes of m. tuberculosis can be grouped based on the presence or absence of the atp lid motif and f box (elements kno ... | 2013 | 23486471 |
| crystal structures identify an atypical two-metal-ion mechanism for uridyltransfer in glmu: its significance to sugar nucleotidyl transferases. | n-acetylglucosamine-1-phosphate uridyltransferase (glmu), exclusive to prokaryotes, is a bifunctional enzyme that synthesizes udp-glcnac-an important component of the cell wall of many microorganisms. uridyltransfer, one of the reactions it catalyzes, involves binding glcnac-1-p, utp and mg(2+) ions; however, whether one or two ions catalyze this reaction remains ambiguous. here, we resolve this using biochemical and crystallographic studies on glmu from mycobacterium tuberculosis (glmu(mtb)) an ... | 2013 | 23485416 |
| tumour necrosis factor-alpha and nitric oxide response in different categories of tuberculosis patients. | to compare the magnitude of tumour necrosis factor alpha (tnf-α) and nitric oxide (no) response in different categories of active tuberculosis (tb) patients by ex vivo experiment. | 2013 | 23485383 |
| the benefits to communities and individuals of screening for active tuberculosis disease: a systematic review. | screening for tuberculosis (tb) disease aims to improve early tb case detection. the ultimate goal is to improve outcomes for people with tb and to reduce mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. before screening programmes are recommended, evidence is needed of individual and/or community-level benefits. | 2013 | 23485377 |
| passive administration of purified secretory iga from human colostrum induces protection against mycobacterium tuberculosis in a murine model of progressive pulmonary infection. | immunoglobulin a is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. the high concentration of human secretory iga (hsiga) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections. | 2013 | 23458564 |
| phage display of functional αβ single-chain t-cell receptor molecules specific for cd1b:ac₂sgl complexes from mycobacterium tuberculosis-infected cells. | the development of molecules specific for m. tuberculosis-infected cells has important implications, as these tools may facilitate understanding of the mechanisms regulating host pathogen interactions in vivo. in addition, development of new tools capable to targeting m. tuberculosis-infected cells may have potential applications to diagnosis, treatment, and prevention of tuberculosis (tb). due to the lack of cd1b polymorphism, m. tuberculosis lipid-cd1b complexes could be considered as universa ... | 2013 | 23458512 |
| in silico identification of m. tb proteins with diagnostic potential. | tb, caused by mycobacterium tuberculosis (mtb), is one of the major global infectious diseases. for the pandemic control, early diagnosis with sensitive and specific methods is fundamental. with the advent of bioinformatics' tools, the identification of several proteins involved in the pathogenesis of tb (tb) has been possible. in the present work, the mtb genome was explored to look for molecules with possible antigenic properties for their evaluation as part of new generation diagnostic kits b ... | 2013 | 23458073 |
| rp105 involved in activation of mouse macrophages via tlr2 and tlr4 signaling. | rp105 is a member of the toll-like receptor family of proteins that transmits an activation signal in b cells, playing a role in regulation of b cell growth and death; in macrophages and dendritic cells, rp105 is a specific inhibitor of tlr4 signaling. rp105 is uniquely important for regulating tlr4-dependent signaling. it also proved that rp105 is closely related to tlr2 in macrophage activation by mycobacterium tuberculosis lipoproteins. the aim of our study is to investigate the role of rp105 ... | 2013 | 23483427 |
| the viable mycobacterium tuberculosis h37ra strain induces a stronger mouse macrophage response compared to the heat-inactivated h37rv strain. | macrophages are the target cells for mycobacterium tuberculosis (m. tuberculosis) as well as key effector cells for clearance of this pathogen. the aim of the present study was to measure and compare the responses of mouse peritoneal macrophages following exposure to the live m. tuberculosis h37ra and heat-inactivated h37rv strains. in vitro phagocytosis assays indicated that the macrophages had a higher capacity to engulf the live h37ra strain compared to the inactivated h37rv strain. enzyme-li ... | 2013 | 23483126 |
| retropharyngeal abscess coinfected with staphylococcus aureus and mycobacterium tuberculosis after rhinoviral infection in a 1-month-old infant. | a retropharyngeal abscess is a rare disease entity in young infants but can develop after nasopharyngeal viral infection. group b streptococcus and staphylococcus aureus are the most common pathogens in young infants, however, mycobacterium tuberculosis is very rare. we report the case of retropharyngeal abscess and coinfection with s. aureus and m. tuberculosis in a very young infant presenting with respiratory symptoms due to upper airway obstruction. usually tuberculous retropharyngeal absces ... | 2013 | 23482861 |
| central nervous system tuberculosis: a disease from papua new guinea in north queensland. | to describe cases of confirmed central nervous system (cns) tuberculosis seen at the major tertiary referral centre of north queensland over a 10-year period. | 2013 | 23480051 |
| the pup-proteasome system of mycobacterium tuberculosis. | proteasomes are atp-dependent protein degradation machines present in all archaea and eukaryotes, and found in several bacterial species of the order actinomycetales. mycobacterium tuberculosis (mtb), an actinomycete pathogenic to humans, requires proteasome function to cause disease. in this chapter, we describe what is currently understood about the biochemistry of the mtb proteasome and its role in virulence. the characterization of the mtb proteasome has led to the discovery that proteins ca ... | 2013 | 23479444 |
| new sputum metabolite markers implicating adaptations of the host to mycobacterium tuberculosis, and vice versa. | in this study, a metabolomics research approach was used to identify new tuberculosis (tb) markers from sputum, in an attempt to better characterise the disease as well as the metabolic response of the host to mycobacterium tuberculosis infection. after gcxgc-tofms analyses, various multivariate and univariate statistical methods were implemented to identify those compounds best describing the variation between the tb-positive and tb-negative patient groups. the interpretation of these new metab ... | 2013 | 23477940 |
| a rational approach to identify inhibitors of mycobacterium tuberculosis enoyl acyl carrier protein reductase. | mycobacterial enoyl acyl carrier protein (acp) reductase is an attractive target for focused design of novel antitubercular agents. structural information available on enoyl-acp reductase in complex with different ligands was used to generate receptor-based pharmacophore model in discovery studio (ds). in parallel, pharmacophore models were also generated using ligand-based approach (hypogen module in ds). statistically significant models were generated (r(2) = 0.85) which were found to be predi ... | 2013 | 23477735 |
| molecular typing of mycobacteria isolated from extrapulmonary tuberculosis patients at debre birhan referral hospital, central ethiopia. | extrapulmonary tuberculosis (eptb) constitutes about 10% to 20% of all cases of tuberculosis in immunocompetent patients and more than 50% of the cases in hiv-positive individuals worldwide. little information is available on the clonal diversity of mycobacterium species in ethiopia from eptb. | 2013 | 23477546 |
| point prevalence and incidence of mycobacterium tuberculosis complex in captive elephants in the united states of america. | captive elephants infected with tuberculosis are implicated as an occupational source of zoonotic tuberculosis. however, accurate estimates of prevalence and incidence of elephant tuberculosis from well-defined captive populations are lacking in the literature. studies published in recent years contain a wide range of prevalence estimates calculated from summary data. incidence estimates of elephant tuberculosis in captive elephants are not available. | 2013 | 23477422 |
| ssaa, a member of a novel class of transcriptional regulators, controls sansanmycin production in streptomyces sp. strain ss through a feedback mechanism. | sansanmycins, produced by streptomyces sp. strain ss, are uridyl peptide antibiotics with activities against pseudomonas aeruginosa and multidrug-resistant mycobacterium tuberculosis. in this work, the biosynthetic gene cluster of sansanmycins, comprised of 25 open reading frames (orfs) showing considerable amino acid sequence identity to those of the pacidamycin and napsamycin gene cluster, was identified. ssaa, the archetype of a novel class of transcriptional regulators, was characterized in ... | 2013 | 23475969 |
| non-sporulating ftsz mutants in streptomyces coelicolor reveal amino acid residues critical for ftsz polymerization dynamics. | during sporulation of streptomyces coelicolor, the cytokinetic protein ftsz is assembled into dozens of regularly spaced z rings, which orchestrate the division of aerial hyphae into spores. we have previously found that a missense allele of ftsz, ftsz17(spo), primarily affects sporulation septation rather than formation of cross-walls in vegetative mycelium. to clarify what aspect of ftsz function is compromised in such non-sporulating mutants, we here use a genetic strategy to identify new fts ... | 2013 | 23475952 |
| genetic and mass spectrometric tools for elucidating the physiological function(s) of cytochrome p450 enzymes from mycobacterium tuberculosis. | tuberculosis remains a leading cause of human mortality. the emergence of strains of mycobacterium tuberculosis (mtb), the causative agent, that are resistant to first- and second-line antitubercular drugs urges the development of new therapeutics. the genome of mtb encodes 20 cytochrome p450 enzymes, at least some of which are potential candidates (cyp121, cyp125, and cyp128) for drug targeting. in this regard, we examined the specific role of cyp125 in the cholesterol degradation pathway, usin ... | 2013 | 23475669 |
| mycobacterium tuberculosis exploits human interferon γ to stimulate macrophage extracellular trap formation and necrosis. | human neutrophils form extracellular traps during m. tuberculosis infection, but a similar phenomenon has not been reported in human macrophages. here we demonstrate that m. tuberculosis induces release of extracellular traps from human macrophages. this process is regulated by elastase activity, previously shown to regulate formation of extracellular traps by neutrophils. interestingly, formation of extracellular traps by macrophages during m. tuberculosis infection is inducible by interferon γ ... | 2013 | 23475311 |
| scale-up from shake flasks to bioreactor, based on power input and streptomyces lividans morphology, for the production of recombinant apa (45/47 kda protein) from mycobacterium tuberculosis. | culture conditions in shake flasks affect filamentous streptomyces lividans morphology, as well the productivity and o-mannosylation of recombinant ala-pro-rich o-glycoprotein (known as the 45/47 kda or apa antigen) from mycobacterium tuberculosis. in order to scale up from previous reported shake flasks to bioreactor, data from the literature on the effect of agitation on morphology of streptomyces strains were used to obtain gassed volumetric power input values that can be used to obtain a mor ... | 2013 | 23475258 |
| synthesis and biological evaluation of trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1h-inden-4-yloxyalkylamine derivatives against drug susceptible, non-replicating m. tuberculosis h37rv and clinical multidrug resistant strains. | synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1h-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of mycobacterium tuberculosis have been reported. all the new compounds in the series exhibited mic between 1.56 and 6.25 μg/ml. two compounds 1i and 1j with low mic and low cytotoxicity showed significant reduction in cfu in infected mouse macrophages at 1× mic concentration. the compoun ... | 2013 | 23474387 |
| anti-tuberculosis neolignans from piper regnellii. | the present study determined the anti-mycobacterium tuberculosis activities of supercritical co2 extracts, neolignans eupomatenoid-5 (1), conocarpan (4) and eupomatenoid-3 (7) and their derivatives (2, 3, 5, 6, and 8) from piper regnellii, as well as their cytotoxicities. the supercritical co2 extract from leaves was purified by chromatographic methods, yielding compounds (1), (4) and (7), which were identified by (1)h nmr and comparison with literature data. anti-m. tuberculosis activity (h37rv ... | 2013 | 23474218 |
| evidence supporting a role for dormant bacteria in the pathogenesis of spondylarthritis. | spondylarthritis is still viewed as a reaction to infectious agents, as opposed to an infection by persistent bacteria, for several reasons: (a) an infection is considered proven only when the organism can be cultured; (b) no studies have identified dormant bacteria in the tissues targeted by spondylarthritis; (c) the bacterial persistence hypothesis has no therapeutic implications at the time being, since antibiotics are effective neither on dormant bacteria nor on the manifestations of spondyl ... | 2013 | 23473929 |
| tuberculosis in medical doctors - a study of personal experiences and attitudes. | the concurrent tb and hiv epidemics in sub-saharan africa place all health care workers (hcws) at increased risk of exposure to mycobacterium tuberculosis. | 2013 | 23472695 |
| clonal expansions of cd8+ t cells with il-10 secreting capacity occur during chronic mycobacterium tuberculosis infection. | the exact role of cd8(+) t cells during mycobacterium tuberculosis (mtb) infection has been heavily debated, yet it is generally accepted that cd8(+) t cells contribute to protection against mtb. in this study, however, we show that the mtb-susceptible cba/j mouse strain accumulates large numbers of cd8(+) t cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (pd-1(+), tim-3(+), cd122(+)). cd8(+) t cell expansions from the lungs ... | 2013 | 23472214 |
| transcription of genes involved in sulfolipid and polyacyltrehalose biosynthesis of mycobacterium tuberculosis in experimental latent tuberculosis infection. | the influence of trehalose-based glycolipids in the virulence of mycobacterium tuberculosis (mtb) is recognised; however, the actual role of these cell-wall glycolipids in latent infection is unknown. as an initial approach, we determined by two-dimensional thin-layer chromatography the sulfolipid (sl) and diacyltrehalose/polyacyltrehalose (dat/pat) profile of the cell wall of hypoxic mtb. then, qrt-pcr was extensively conducted to determine the transcription profile of genes involved in the bio ... | 2013 | 23472191 |
| use of whole genome sequencing to determine the microevolution of mycobacterium tuberculosis during an outbreak. | current tools available to study the molecular epidemiology of tuberculosis do not provide information about the directionality and sequence of transmission for tuberculosis cases occurring over a short period of time, such as during an outbreak. recently, whole genome sequencing has been used to study molecular epidemiology of mycobacterium tuberculosis over short time periods. | 2013 | 23472164 |
| early and efficient detection of mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. | early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. these methods to detect m. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. in a developing-country setting, we prospectively evaluated two methods for culturing and detecting m. tuberculosis in sputum. sputum samples were cultured in liquid assay (micro broth culture) ... | 2013 | 23469014 |
| digital pcr to detect and quantify heteroresistance in drug resistant mycobacterium tuberculosis. | drug resistance in mycobacterium tuberculosis presents an enormous public health threat. it is typically defined as >1% of drug resistant colonies using the agar proportion method. detecting small numbers of drug resistant tb in a population, also known as heteroresistance, is challenging with current methodologies. here we have utilized digital pcr to detect heteroresistance within m. tuberculosis populations with excellent accuracy versus the agar proportion method. we designed dual taqman-mgb ... | 2013 | 23468945 |
| immunization strategies against pulmonary tuberculosis: considerations of t cell geography. | pulmonary tuberculosis (tb) remains a global health concern with an astounding 9 million new cases and 2 million deaths per year. this leading infectious cause of death remains highly prevalent with one third of the world's population latently infected with mycobacterium tuberculosis (m.tb) despite routine vaccination against tb in endemic areas. the only approved tb vaccine is the bacille calmette-guerin (bcg), which provides protection against childhood miliary tuberculosis and has been admini ... | 2013 | 23468114 |
| cd1d and natural killer t cells in immunity to mycobacterium tuberculosis. | the critical role of peptide antigen-specific t cells in controlling mycobacterial infections is well documented in natural resistance and vaccine-induced immunity against mycobacterium tuberculosis. however, many other populations of leukocytes contribute to innate and adaptive immunity against mycobacteria. among these, non-conventional t cells recognizing lipid antigens presented by the cd1 antigen presentation system have attracted particular interest. in this chapter, we review the basic im ... | 2013 | 23468111 |
| foxp3(+) regulatory t cells in tuberculosis. | the immune response to mycobacterium tuberculosis (mtb) must be tightly regulated to mount a sufficient response to limit bacterial growth and dissemination while avoiding excessive inflammation that could damage host tissues. a wide variety of cell types, cell surface molecules, and cytokines are likely to contribute to this regulation, but recent studies have revealed that a subset of cd4 t cells expressing the transcription factor foxp3, called regulatory t (reg) cells, play a critical role [ ... | 2013 | 23468109 |
| antigen-specific cd8(+) t cells and protective immunity to tuberculosis. | the continuing hiv/aids epidemic and the spread of multi-drug resistant mycobacterium tuberculosis has led to the perpetuation of the worldwide tuberculosis epidemic. while m. bovis bcg is widely used as a vaccine, it lacks efficacy in preventing pulmonary tuberculosis in adults [1]. to combat this ongoing scourge, vaccine development for tuberculosis is a global priority. most infected individuals develop long-lived protective immunity, which controls and contains m. tuberculosis in a t cell-de ... | 2013 | 23468108 |
| dying to live: how the death modality of the infected macrophage affects immunity to tuberculosis. | virulent mycobacterium tuberculosis (mtb) inhibits apoptosis and triggers necrosis of host macrophages to evade innate delay in the initiation of adaptive immunity. necrosis is a mechanism used by bacteria to exit macrophage, evade the host defenses, and disseminate while apoptosis is associated with diminished pathogen viability. we have recently demonstrated that eicosanoids regulate cell death program of either human or murine macrophages infected with mtb. we have defined prostaglandin e2 (p ... | 2013 | 23468106 |
| mycobacterium tuberculosis genes involved in regulation of host cell death. | the topic of host cell death response upon mycobacterium tuberculosis (mtb) infection has been a controversial one [1]. recent findings demonstrate that one of the important confounding factors was most likely the fact that while mtb inhibits host cell apoptosis induction early during the infection it clearly induces a necrotic form of cell death during later infection stages [2, 3]. this bi-phasic intracellular lifestyle in regard to host cell death manipulation is emerging as a common theme sh ... | 2013 | 23468105 |
| evolution of mycobacterium tuberculosis. | genomic studies have provided a refined understanding of the genetic diversity within the mycobacterium genus, and more specifically within mycobacterium tuberculosis. these results have informed a new perspective on the macro- and micro-evolution of the tubercle bacillus. in the first step, a m. kansasii-like opportunistic pathogen acquired new genes, through horizontal gene transfer, that enabled it to better exploit an intracellular niche and ultimately evolve into a professional pathogen. in ... | 2013 | 23468104 |
| genetic determinants of susceptibility to mycobacterial infections: irf8, a new kid on the block. | genetic and population studies suggest that onset, progression and ultimate outcome of infection with mycobacteria, including the agent of tuberculosis mycobacterium tuberculosis, are strongly influenced by genetic factors. family-based and case-control linkage and association studies have suggested a complex genetic component for susceptibility to tuberculosis. on the other hand, patients with inborn errors in the il12/ifnγ circuit may develop disseminated mycobacterial infections following per ... | 2013 | 23468103 |
| interaction between dahp synthase and chorismate mutase endows new regulation on dahp synthase activity in corynebacterium glutamicum. | previous research on corynebacterium glutamicum revealed that 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (dscg, formerly ds2098) interacts with chorismate mutase (cmcg, formerly cm0819). in this study, we investigated the interaction by means of structure-guided mutation and enzymatic assays. our results show that the interaction imparted a new mechanism for regulation of dahp activity: in the absence of cmcg, dscg activity was not regulated by prephenate, whereas in the presence of cm ... | 2013 | 23467831 |
| performance of the genotype mtbdrplus assay directly on sputum specimens from brazilian patients with tuberculosis treatment failure or relapse. | rapid identification of drug resistance in clinical isolates of mycobacterium tuberculosis is important in determining treatment for tuberculosis. the aim of this work was evaluate the performance of the genotype mdrtbplus assay directly on sputum of patients who had treatment failure or relapse in a routine outpatient setting in southern brazil. | 2013 | 23467605 |
| clinical value of is6110-based loop-mediated isothermal amplification for detection of mycobacterium tuberculosis complex in respiratory specimens. | a fundamental to global tuberculosis (tb) control is timely and accurate diagnosis of infectious cases of the disease. among various methods, techniques based on nucleic acid amplification are the ones with promising prospects. the present study evaluates the diagnostic value of the recently developed is6110-based loop-mediated isothermal amplification (lamp) for detection of mycobacterium tuberculosis complex (mtbc) in sputum specimens. | 2013 | 23466595 |
| mycobacterium tuberculosis infections in solid organ transplantation. | | 2013 | 23465000 |
| discovery of novel inha reductase inhibitors: application of pharmacophore- and shape-based screening approach. | inha is a promising and attractive target in antimycobacterial drug development. inha is involved in the reduction of long-chain trans-2-enoyl-acp in the type ii fatty acid biosynthesis pathway of mycobacterium tuberculosis. recent studies have demonstrated that inha is one of the targets for the second line antitubercular drug ethionamide. | 2013 | 23464516 |
| thioridazine lacks bactericidal activity in an animal model of extracellular tuberculosis. | the antipsychotic drug thioridazine is active in the murine model of tuberculosis infection, which is predominantly intracellular in nature. recent clinical reports suggest that thioridazine may play a role in the treatment of drug-resistant tuberculosis. we studied the tuberculocidal activity of thioridazine in guinea pigs, which develop necrotic lung granulomas histologically resembling their human counterparts. | 2013 | 23463208 |
| ifnγ/tnfα specific-cells and effector memory phenotype associate with active tuberculosis. | controversial results were reported on the role of polyfunctional t-cells in tuberculosis (tb). our aim was to simultaneously characterize the mycobacterium tuberculosis (mtb)-specific immune response as cytokine production and memory phenotype by flow cytometry after in vitro stimulation with region of difference 1 ("rd1") recombinant proteins (esat-6 and cfp-10) in patients at different tb stage in a low tb endemic country. to assess the specificity of these findings, we evaluated the response ... | 2013 | 23462597 |
| antitubercular diterpenoids from vitex trifolia. | a new halimane diterpenoid, 13-hydroxy-5(10),14-halimadien-6-one (1) and two new labdane diterpenoids, 6α,7α-diacetoxy-13-hydroxy-8(9),14-labdadien (2) and 9-hydroxy-13(14)-labden-15,16-olide (3), were isolated for the first time, along with fifteen known compounds, from the hexane soluble fraction of methanolic extract of vitex trifolia leaves. the structures of these new diterpenoids were elucidated by spectral analysis. their relative configurations were established using analysis of noesy co ... | 2013 | 23462211 |
| a chemical proteomics approach to profiling the atp-binding proteome of mycobacterium tuberculosis. | tuberculosis, caused by mycobacterium tuberculosis, remains one of the leading causes of death worldwide despite extensive research, directly observed therapy using multidrug regimens, and the widespread use of a vaccine. the majority of patients harbor the bacterium in a state of metabolic dormancy. new drugs with novel modes of action are needed to target essential metabolic pathways in m. tuberculosis; atp-competitive enzyme inhibitors are one such class. previous screening efforts for atp-co ... | 2013 | 23462205 |
| il-22 is mainly produced by ifnγ-secreting cells but is dispensable for host protection against mycobacterium tuberculosis infection. | anti-inflammatory treatment of autoimmune diseases is associated with an increased risk of reactivation tuberculosis (tb). besides interleukin (il-17)a, il-22 represents a classical t helper (th)17 cytokine and shares similar pathological effects in inflammatory diseases such as psoriasis or arthritis. whereas il-17a supports protective immune responses during mycobacterial infections, the role of il-22 after infection with mycobacterium tuberculosis (mtb) is yet poorly characterized. therefore, ... | 2013 | 23460846 |
| treatment of latent tuberculosis infection. | latent tuberculosis infection (ltbi) refers to a circumstance in which viable mycobacterium tuberculosis (mtb) bacilli are present in an individual but symptoms and signs of active disease are lacking, and the bacilli are relatively inactive metabolically. in favorable circumstances, some of these inactive bacilli resume greater metabolic activity and replication, leading to the development of active tuberculosis disease. treatment of this condition (tltbi) is designed to prevent (soon, or in th ... | 2013 | 23460007 |
| management of multidrug resistant tuberculosis. | drug-resistant strains of mycobacterium tuberculosis have emerged as a major threat to global tuberculosis control. despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment has allowed m. tuberculosis to acquire resistance to our most important antituberculosis drugs. the epidemic of drug-resistant tuberculosis has spread quickly in some areas due to the convergence of resistant strains of m. tuberculosis in high-risk patient ... | 2013 | 23460005 |
| mycobacterium tuberculosis may escape helper t cell recognition by infecting human fibroblasts. | the host immune response can limit mycobacterium tuberculosis (mtb) spreading in primary tuberculosis (tb) without eradicating all bacilli, which can persist causing latent tb infection and are responsible for reactivation tb. persistent mtb is confined to granulomas within phagocytes, but it is also found in other non-immune cells. we focused on fibroblasts since these cells participate to the granuloma formation and were shown to be infected in latent tb infections. we show that in vitro both ... | 2013 | 23459076 |
| central nervous system and spinal tuberculosis in children at a tertiary care center in saudi arabia. | tuberculosis (tb) remains a global health problem. there is limited data on pediatric central nervous system tuberculosis (cnstb) in saudi arabia on diagnosis and therapy. | 2013 | 23458932 |
| mycobacterium tuberculosis-specific cd8+ t cells are functionally and phenotypically different between latent infection and active disease. | protective immunity to mycobacterium tuberculosis (mtb) remains poorly understood and the role of mtb-specific cd8(+) t cells is controversial. here we performed a broad phenotypic and functional characterization of mtb-specific cd8(+) t cells in 326 subjects with latent mtb infection (ltbi) or active tb disease (tb). mtb-specific cd8(+) t cells were detected in most (60%) tb patients and few (15%) ltbi subjects but were of similar magnitude. mtb-specific cd8(+) t cells in ltbi subjects were mos ... | 2013 | 23456989 |
| nasopharyngeal tuberculosis. | today, the opportunity to see tuberculosis is decreasing. nasopharyngeal tuberculosis is a rare entity, even in endemic tuberculosis areas. a case of nasopharyngeal tuberculosis is described. a 28-year-old woman presented with a sore throat. irregular mucosal thickening was seen in the nasopharynx. staining for acid-fast bacilli was positive (gaffky 1), and the pcr test was positive for mycobacterium tuberculosis from pharyngeal mucus. computed tomography showed mucosal thickening in the pharynx ... | 2013 | 23456205 |
| synthesis and biological evaluation of a new class of 4-aminoquinoline-rhodanine hybrid as potent anti-infective agents. | synthesis of novel 4-aminoquinoline-rhodanine hybrid using inexpensive starting materials via easy to operate methodology, and their biological activity is reported. all the compounds were screened for their in vitro antimalarial activity against chloroquine-resistant (k1) and chloroquine-sensitive (3d7) strains of plasmodium falciparum, and their cytotoxicity toward vero cell line. compounds 9, 19, 21 and 23 exhibited excellent antimalarial activity with ic50 value ranging from 13.2 to 45.5 nm ... | 2013 | 23454512 |
| rapid determination of growth inhibition of mycobacterium tuberculosis by gc-ms/ms quantitation of tuberculostearic acid. | classical determination of growth inhibition of mycobacterium tuberculosis in macrophages and mice by new candidate anti-tb drugs utilizes the determination of colony forming units (cfus) from lung homogenates, a labor-intensive process requiring 2-3 weeks incubation. qualitative analysis of tuberculostearic acid (tbsa), a cell wall associated biomarker found in m. tuberculosis, has been investigated for clinical diagnosis of tuberculosis (tb) but few reports exist of attempts to quantitate tbsa ... | 2013 | 23454100 |
| can mycobacterial katg genetic changes in isoniazid-resistant tuberculosis influence human disease features? | isoniazid-resistant (inhr) mycobacterium tuberculosis isolates often have katg mutations, and katg is a virulence factor in animal models. it is unclear if katg mutations or other mutations influence the characteristics of human disease. | 2013 | 23453008 |
| human il10 gene repression by rev-erbα ameliorates mycobacterium tuberculosis clearance. | nuclear receptors modulate macrophage effector functions, which are imperative for clearance or survival of mycobacterial infection. the adopted orphan nuclear receptor rev-erbα is a constitutive transcriptional repressor as it lacks af2 domain and was earlier shown to be present in macrophages. in the present study, we highlight the differences in the relative subcellular localization of rev-erbα in monocytes and macrophages. the nuclear localization of rev-erbα in macrophages is subsequent to ... | 2013 | 23449984 |
| evidence for diversifying selection in a set of mycobacterium tuberculosis genes in response to antibiotic- and nonantibiotic-related pressure. | tuberculosis (tb) is a global health problem estimated to kill 1.4 million people per year. recent advances in the genomics of the causative agents of tb, bacteria known as the mycobacterium tuberculosis complex (mtbc), have allowed a better comprehension of its population structure and provided the foundation for molecular evolution analyses. these studies are crucial for a better understanding of tb, including the variation of vaccine efficacy and disease outcome, together with the emergence o ... | 2013 | 23449927 |
| ppe2 protein of mycobacterium tuberculosis may inhibit nitric oxide in activated macrophages. | although the pathophysiological role of pe/ppe proteins of mycobacterium tuberculosis is yet to be fully understood, recent evidence shows that these proteins play important roles in antigenic diversity, as well as in host-pathogen interactions and mycobacterial pathogenesis. most of the pe/ppe proteins are highly expressed in pathogenic bacteria, pointing to their role in the pathogenesis of mycobacteria. here, we provide an overview of our work in progress on a specific ppe protein, ppe2 (rv02 ... | 2013 | 23448669 |
| molecular immunologic correlates of spontaneous latency in a rabbit model of pulmonary tuberculosis. | infection of humans with mycobacterium tuberculosis (mtb) results in latent tuberculosis infection (ltbi) in 90-95% of immune competent individuals, with no symptoms of active disease. the world health organization estimates that 1.5 billion people have ltbi, which can reactivate in the setting of waning host immunity, posing a threat to global tb control. various animal models have been used to study the pathogenesis of tb. however, besides nonhuman primates, rabbits are the only animal model t ... | 2013 | 23448601 |
| alox5 is associated with tuberculosis in a subset of the pediatric population of north china. | genetic factors are involved in the etiology of mycobacterium tuberculosis infection. recently, alox5 has been identified as a candidate gene for tuberculosis (tb) susceptibility. we investigated whether an association between alox5 and tb exists in a chinese pediatric population from northern china. | 2013 | 23448388 |
| can molecular methods detect 1% isoniazid resistance in mycobacterium tuberculosis? | patients may harbor both drug-susceptible and -resistant bacteria, representing heteroresistance. we studied mixtures of isoniazid-resistant and -susceptible mycobacterium tuberculosis strains. conventional drug susceptibility testing was the most sensitive method of detection, whereas the line probe assay and sequencing were not able to detect the clinically relevant 1% proportion of resistant bacteria. | 2013 | 23447641 |
| modulation of the phenotype and function of mycobacterium tuberculosis-stimulated dendritic cells by adrenal steroids. | cell-mediated immunity, cytokines induced during the specific immune response and t-cell populations are crucial factors for containing mycobacterium tuberculosis infection. recent reports suggest a cross-regulation between adrenal steroids (glucocorticoids and dehydroepiandrosterone, dhea) and the function of antigen-presenting cells (apcs). therefore, we investigated the role of adrenal hormones on the functional capacity of m. tuberculosis-induced dendritic cells (dcs). cortisol significantly ... | 2013 | 23446847 |
| inferring patient to patient transmission of mycobacterium tuberculosis from whole genome sequencing data. | mycobacterium tuberculosis is characterised by limited genomic diversity, which makes the application of whole genome sequencing particularly attractive for clinical and epidemiological investigation. however, in order to confidently infer transmission events, an accurate knowledge of the rate of change in the genome over relevant timescales is required. | 2013 | 23446317 |