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fluoroquinolone consumption and -resistance trends in mycobacterium tuberculosis and other respiratory pathogens: ecological antibiotic pressure and consequences in pakistan, 2009-2015.fluoroquinolones (fqs) are important anti-tuberculous drugs for the treatment of multidrug-resistant (mdr) tuberculosis. resistance to fqs leads to fewer options for treatment of tuberculosis (tb), and infection with such strains may also require longer treatment duration. trends of resistance in mycobacterium tuberculosis (mtb) are indicators of mtb-resistance evolution. drivers of such resistance need to be understood and studied to inform preventive strategies.201627931682
trend of bacterial meningitis in bahrain from 1990 to 2013 and effect of introduction of new vaccines.meningitis is among the 10 commonest infectious causes of death worldwide. this retrospective analysis of reported cases of meningitis in bahrain aimed to assess the trend in the incidence of bacterial meningitis from 1990 to 2013, before and after the introduction of new vaccines. of 1455 reported cases of meningitis during the study period 73.1% were viral and 26.9% were bacterial etiology (tuberculous meningitis 8.3%; streptococcus pneumoniae 4.9%, haemophilus influenzae 3.6% and neisseria me ...201627334074
a case of good's syndrome presenting with pulmonary tuberculosis.adult onset immunodeficiency associated with thymoma is a rare condition. the combination of hypogammaglobulinemia, reduced number of peripheral b and cd4+ t cells, along with thymoma constitutes good's syndrome (gs). this immunodeficiency condition is often complicated with opportunistic infection with organisms, like bacteria (haemophilus influenzae, streptococcus pneumonia etc), viruses (cytomegalovirus, herpes simplex etc), fungi and protozoa. we present an unusual case of good's syndrome wi ...201627164735
usage of murine t-cell hybridoma cells as responder cells reveals interference of helicobacter pylori with human dendritic cell-mediated antigen presentation.direct effects of helicobacter pylori (h. pylori) on human cd4(+) t-cells hamper disentangling a possible bacterial-mediated interference with major histocompatibility complex class ii (mhc-ii)-dependent antigen presentation to these cells. to overcome this limitation, we employed a previously described assay, which enables assessing human antigen-processing cell function by using murine t-cell hybridoma cells restricted by human leukocyte antigen (hla) alleles. hla-dr1(+) monocyte-derived dendr ...201627980859
freezing the dynamic gap for selectivity: motion-based design of inhibitors of the shikimate kinase enzyme.shikimate kinase (sk), the fifth enzyme of the aromatic amino acid biosynthesis, is a recognized target for antibiotic drug discovery. the potential of the distinct dynamic apolar gap, which isolates the natural substrate from the solvent environment for catalysis, and the motion of mycobacterium tuberculosis and helicobacter pylori sk enzymes, which was observed by molecular dynamics simulations, was explored for inhibition selectivity. the results of the biochemical and computational studies r ...201627699905
stool microbiome reveals diverse bacterial ureases as confounders of oral urea breath testing for helicobacter pylori and mycobacterium tuberculosis in bamako, mali.detection of bacterial urease activity has been utilized successfully to diagnose helicobacter pylori (h. pylori). while mycobacterium tuberculosis (m. tuberculosis) also possesses an active urease, it is unknown whether detection of mycobacterial urease activity by oral urease breath test (ubt) can be exploited as a rapid point of care biomarker for tuberculosis (tb) in humans. we enrolled 34 individuals newly diagnosed with pulmonary tb and 46 healthy subjects in bamako, mali and performed ora ...201627532494
targeting the motion of shikimate kinase: development of competitive inhibitors that stabilize an inactive open conformation of the enzyme.the large conformational changes observed by molecular dynamics simulation studies on the product release in the lid and shikimic acid binding (sb) domains of the shikimate kinase (sk) enzyme have been exploited in the development of reversible competitive inhibitors against sk from mycobacterium tuberculosis and helicobacter pylori. this enzyme is a recognized target for antibiotic drug discovery. the reported c5-substituted shikimic acid analogues interact with the dynamic apolar pocket that s ...201627191386
study of the phosphoryl-transfer mechanism of shikimate kinase by nmr spectroscopy.the phosphoryl-transfer mechanism of shikimate kinase from mycobacterium tuberculosis and helicobacter pylori, which is an attractive target for antibiotic drug discovery, has been studied by 1d (1)h and (31)p nmr spectroscopy. metaphosphoric acid proved to be a good mimetic of the metaphosphate intermediate and facilitated the ready and rapid evaluation by nmr spectroscopic analysis of a dissociative mechanism. the required closed form of the active site for catalysis was achieved by the use of ...201626797764
inhibition of shikimate kinase and type ii dehydroquinase for antibiotic discovery: structure-based design and simulation studies.the loss of effectiveness of current antibiotics caused by the development of drug resistance has become a severe threat to public health. current widely used antibiotics are surprisingly targeted at a few bacterial functions - cell wall, dna, rna, and protein biosynthesis - and resistance to them is widespread and well identified. there is therefore great interest in the discovery of novel drugs and therapies to tackle antimicrobial resistance, in particular drugs that target other essential pr ...201626303426
[molecular epidemiology studies on the immigrant population in spain].molecular epidemiology is a new scientific discipline which allows to integrate information on the genetic variation of infectious pathogens with their diffusion in a population and its subgroups including, for instance, resistance mutations to antibiotics and antiretrovirals. we present the results of an analysis of scientific publications that analyze the health status of the immigrant population in spain from a molecular epidemiology perspective.201625418571
a label-free method for the detection of specific dna sequences using gold nanoparticles bifunctionalized with a chemiluminescent reagent and a catalyst as signal reporters.sensitive, specific, simple, fast, and low-cost dna detection methods are extremely important in clinical diagnostics, gene therapy, and a variety of biomedical studies. in this work, we developed a general method for the detection of specific dna sequences from mycobacterium tuberculosis (tb), hepatitis b virus (hbv), and myelocytomatosis viral oncogene (v-myc) using gold nanoparticles bifunctionalized with both a chemiluminescent (cl) reagent and a catalytic metal complex as signal reporters a ...201626753973
siv infection facilitates mycobacterium tuberculosis infection of rhesus macaques.tuberculosis (tb) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (hiv)-infected patients. thus, it is necessary to understand the pathogenetic interactions between m.tb and hiv infection. in this study, we examined m.tb and/or simian immunodeficiency virus (siv) infection of chinese rhesus macaques. while there was little evidence that m.tb enhanced siv infection of macaques, siv could facilitate m.tb infection as demonstrated by x-rays, patho ...201628133458
notes from the field: lymphocytic choriomeningitis virus meningoencephalitis from a household rodent infestation - minnesota, 2015.on april 20, 2015, a female aged 15 years sought care at her pediatrician's office after 5 days of fever, myalgia, left parietal headache, and photophobia. a rapid influenza assay was negative, and erythrocyte sedimentation rate and total white blood cell count were normal. she improved with symptomatic care at home, but returned to her pediatrician's office on april 28, reporting recurrence of her headache and photophobia and new onset of a stiff neck. she was admitted to the hospital, where sh ...201626963688
infergen stimulated macrophages restrict mycobacterium tuberculosis growth by autophagy and release of nitric oxide.ifn alfacon-1 (infergen) is a synthetic form of interferon (ifn)-α2b. infergen has immunomodulatory activity and is effective against hepatitis c virus. however, the effect of infergen (ifg) on mycobacterium tuberculosis (mtb) has not yet been reported. therefore, for the first time, we have studied the influence of ifg in constraining the survival of mtb in human macrophages. we observed that ifg significantly enhanced the maturation and activation of macrophages. further, it substantially augm ...201628000752
infectious complications with the use of biologic response modifiers in infants and children.biologic response modifiers (brms) are substances that interact with and modify the host immune system. brms that dampen the immune system are used to treat conditions such as juvenile idiopathic arthritis, psoriatic arthritis, or inflammatory bowel disease and often in combination with other immunosuppressive agents, such as methotrexate and corticosteroids. cytokines that are targeted include tumor necrosis factor α; interleukins (ils) 6, 12, and 23; and the receptors for il-1α (il-1a) and il- ...201627432853
[disseminated histoplasmosis in patients with aids. buenos aires, 2009-2014].a retrospective study was carried out on 171 cases of disseminated histoplasmosis diagnosed in hiv/aids patients during the period 2009-2014. although hiv diagnosis rates remained stable over the study period, a sensible increase in the number of histoplasmosis cases was observed in the last three years. disseminated histoplasmosis was prevalent in males with an average age of 37.8 years. at diagnosis, only 54/171 (31.6%) were receiving haart, and cd4+ t-lymphocyte counts ranged from 4 to 264 ce ...201627959839
ca(ii) binding regulates and dominates the reactivity of a transition-metal-ion-dependent diesterase from mycobacterium tuberculosis.the diesterase rv0805 from mycobacterium tuberculosis is a dinuclear metallohydrolase that plays an important role in signal transduction by controlling the intracellular levels of cyclic nucleotides. as rv0805 is essential for mycobacterial growth it is a promising new target for the development of chemotherapeutics to treat tuberculosis. the in vivo metal-ion composition of rv0805 is subject to debate. here, we demonstrate that the active site accommodates two divalent transition metal ions wi ...201626662456
involvement of il-17a-producing tcr γδ t cells in late protective immunity against pulmonary mycobacterium tuberculosis infection.interleukin (il)-17a is a cytokine originally reported to induce neutrophil-mediated inflammation and anti-microbial activity. the cd4(+) t cells, which produce il-17a, have been well characterized as th17 cells. on the other hand, il-17a-producing tcr γδ(+) t cells have been reported to participate in the immune response at an early stage of infection with listeria monocytogenes and mycobacterium bovis in mice. however, the involvement of il-17a in protective immunity was not clearly demonstrat ...201627980775
listeria monocytogenes encodes a functional esx-1 secretion system whose expression is detrimental to in vivo infection.bacterial pathogenicity deeply depends on the ability to secrete virulence factors that bind specific targets on host cells and manipulate host responses. the gram-positive bacterium listeria monocytogenes is a human foodborne pathogen that remains a serious public health concern. to transport proteins across its cell envelope, this facultative intracellular pathogen engages a set of specialized secretion systems. here we show that l. monocytogenes egde uses a specialized secretion system, named ...201627723420
tlr and tnf-r1 activation of the mkk3/mkk6-p38α axis in macrophages is mediated by tpl-2 kinase.previous studies suggested that toll-like receptor (tlr) stimulation of the p38α map kinase (mapk) is mediated by transforming growth factor-β-activated kinase 1 (tak1) activation of mapk kinases, mkk3, mkk4 and mkk6. we used quantitative mass spectrometry to monitor tumour progression locus 2 (tpl-2)-dependent protein phosphorylation following tlr4 stimulation with lipopolysaccharide, comparing macrophages from wild-type mice and map3k8(d270a/d270a) mice expressing catalytically inactive tpl-2 ...201627402796
sybr green-based detection of leishmania infantum dna using peripheral blood samples.parasitological methods for the diagnosis of visceral leishmaniasis (vl) require invasive sampling procedures. the aim of this study was to detect leishmania infantum (l. infantum) dna by real time-pcr method in peripheral blood of symptomatic vl patient and compared its performance with nested pcr, an established molecular method with very high diagnostic indices. 47 parasitologically confirmed vl patients diagnosed by direct agglutination test (dat > 3200), bone marrow aspiration and presented ...201627065603
topical simvastatin as host-directed therapy against severity of cutaneous leishmaniasis in mice.we recently demonstrated that statins mediate protection against intracellular pathogens, mycobacterium tuberculosis and listeria monocytogenes in mice. here, we investigated the immunomodulatory potential of simvastatin as a topical or systemic host-directed drug therapy in controlling inflammatory responses in an experimental mouse model of cutaneous leishmaniasis caused by leishmania major (lv39). in an ear infection model, topical application of simvastatin directly on established lesions si ...201627632901
a network map of interleukin-10 signaling pathway.interleukin-10 (il-10) is an anti-inflammatory cytokine with important immunoregulatory functions. it is primarily secreted by antigen-presenting cells such as activated t-cells, monocytes, b-cells and macrophages. in biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer il-10 receptor and induces downstream signaling. il-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as burkitt lymphoma, non-hodgkins lymp ...201626253919
recombinant leishmania rab6 (rldrab6) is recognized by sera from visceral leishmaniasis patients.rab proteins form the largest branch of the ras superfamily. rab proteins are key regulators of intracellular vesicular transport and membrane trafficking. although rabgtpases are well-recognized targets in human diseases but are under-explored therapeutically in the leishmania parasite. using a quantitative cytofluorimetric assay, we analyzed the composition and organization of rab6gtpase protein which was found to be primarily localized on the parasite subpellicular membrane and flagellum due ...201627666959
plasma contributes to the antimicrobial activity of whole blood against mycobacterium tuberculosis.the whole blood model for infection has proven useful to analyze the immunological response to mycobacterium tuberculosis, because it exerts a significant antimicrobial activity. although this activity has been generally assumed to be cellular, we have found that the leukocyte fraction of blood from healthy volunteers did not kill the bacilli. we have discovered that plasma was responsible for a large proportion, but not all, of the antimicrobial activity. furthermore, infected monocytes control ...201627554054
evaluation of chemical composition and antileishmanial and antituberculosis activities of essential oils of piper species.essential oils from fresh piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (gc-ms), and a total of 68 components were identified. principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. the composition of the essential oil of piper mosenii was described for the first time. the cytotoxicity of the essential oils was evaluated in peri ...201628009804
evaluation of chemical composition and antileishmanial and antituberculosis activities of essential oils of piper species.essential oils from fresh piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (gc-ms), and a total of 68 components were identified. principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. the composition of the essential oil of piper mosenii was described for the first time. the cytotoxicity of the essential oils was evaluated in peri ...201627973453
synthesis and biological evaluation against mycobacterium tuberculosis and leishmania amazonensis of a series of diaminated terpenoids.we report the synthesis of a series of diaminated terpenoids containing, as side-chain of the diamine core, the "head-to-tail" prenyl derivatives, with amino amino spacers of variable length. in vitro biological activity of these compounds was evaluated against mycobacterium tuberculosis and leishmania amazonensis, and the structure-activity relationships are discussed. different biological results were observed depending on the terpenic side-chain length. the best results were obtained for tran ...201627876209
risk assessment of soulatrolide and mammea (a/ba+a/bb) coumarins from calophyllum brasiliense by a toxicogenomic and toxicological approach.calophyllum brasiliense (calophyllaceae) is a tropical rain forest tree distributed in central and south america. it is an important source of tetracyclic dipyrano coumarins (soulatrolide) and mammea type coumarins. soulatrolide is a potent inhibitor of hiv-1 reverse transcriptase and displays activity against mycobacterium tuberculosis. meanwhile, mammea a/ba and a/bb, pure or as a mixture, are highly active against several human leukemia cell lines, trypanosoma cruzi and leishmania amazonensis ...201626995226
productive hiv-1 infection is enriched in cd4(-)cd8(-) double negative (dn) t cells at pleural sites of dual infection with hiv and mycobacterium tuberculosis.a higher human immunodeficiency virus 1 (hiv-1) viral load at pleural sites infected with mycobacterium tuberculosis (mtb) than in peripheral blood has been documented. however, the cellular source of productive hiv infection in hiv-1/mtb-coinfected pleural fluid mononuclear cells (pfmcs) remains unclear. in this study, we observed significant quantities of hiv-1 p24(+) lymphocytes in pfmcs, but not in peripheral blood mononuclear cells (pbmcs). hiv-1 p24(+) lymphocytes were mostly enriched in d ...201626497177
tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.due to the growing problem of drug resistant mycobacterium tuberculosis strains, coupled with the twinning of tuberculosis (tb) to human immunodeficiency virus/acquired immunodeficiency syndrome (hiv/aids), the burden of tb is now difficult to manage. therefore, new antimycobacterial agents are being sought from natural sources. this review focuses on natural antimycobacterial agents from endophytes and medicinal plants of africa, europe, asia, south america and canada. in the countries mentione ...201626464047
analysis of dominant hiv quasispecies suggests independent viral evolution within spinal granulomas coinfected with mycobacterium tuberculosis and hiv-1 subtype c.extrapulmonary tuberculosis (tb) is a significant public health challenge in south africa and worldwide, largely fuelled by the hiv epidemic. in spinal tb, mycobacteria infect the spinal column without dissemination to the spinal cord. the immune microenvironment, target cell characteristics, and other evolutionary forces within granulomas during hiv/tb coinfection are poorly characterized. we investigated whether spinal tb granulomas represent a sequestered anatomical site where independent hiv ...201626564424
population tailored modification of tuberculosis specific interferon-gamma release assay.blood-based interferon-gamma release assays (igra) identify mycobacterium tuberculosis (mtb) sensitisation with increased specificity, but sensitivity remains impaired in human immunodeficiency virus (hiv) infected persons. the quantiferon-tb gold in-tube test contains peptide 38-55 of rv2654c, based on data indicating differential recognition between tuberculosis patients and bcg vaccinated controls in europe. we aimed to fine map the t cell response to rv2654c with the view of improving sensit ...201626632326
medication errors with antituberculosis therapy in an inpatient, academic setting: forgotten but not gone.tuberculosis, an infectious disease caused by the bacteria mycobacterium tuberculosis, has significant public health implications. despite the decreasing prevalence of tuberculosis cases and the availability of well-established treatment guidelines, errors with antituberculosis medications remain a concern as clinician experience with the infection has waned and the goal of eradicating tuberculosis has remained unfulfilled. whereas inappropriate use of other anti-infective classes has been exten ...201626763664
intensified antituberculosis therapy in adults with tuberculous meningitis.tuberculous meningitis is often lethal. early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. we hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral mycobacterium tuberculosis organisms and decrease the rate of death among patients.201626760084
the immune interaction between hiv-1 infection and mycobacterium tuberculosis.the modulation of tuberculosis (tb)-induced immunopathology caused by human immunodeficiency virus (hiv)-1 coinfection remains incompletely understood but underlies the change seen in the natural history, presentation, and prognosis of tb in such patients. the deleterious combination of these two pathogens has been dubbed a "deadly syndemic," with each favoring the replication of the other and thereby contributing to accelerated disease morbidity and mortality. hiv-1 is the best-recognized risk ...201628084192
[the great imitator. case report].authors present two patients suffering from renal tuberculosis, which caused differential diagnostic problems. the first patient was examined because of fever and left flank pain. computed tomography revealed renal shrinkage on the left side. retrograde pyelography demonstrated ureteric stricture and dilated calices. urine culture showed mycobacterium tuberculosis. two months after initiation of the antituberculotic therapy nephrectomy was performed. the second patient was referred to the depart ...201626895803
mycobacteria clumping increase their capacity to damage macrophages.the rough morphotypes of non-tuberculous mycobacteria have been associated with the most severe illnesses in humans. this idea is consistent with the fact that mycobacterium tuberculosis presents a stable rough morphotype. unlike smooth morphotypes, the bacilli of rough morphotypes grow close together, leaving no spaces among them and forming large aggregates (clumps). currently, the initial interaction of macrophages with clumps remains unclear. thus, we infected j774 macrophages with bacterial ...201627757105
fluorescent reporter ds6a mycobacteriophages reveal unique variations in infectibility and phage production in mycobacteria.mycobacteriophage ds6a is unique among the more than 8,000 isolated mycobacteriophages due to its ability to form plaques exclusively on mycobacteria belonging to the mycobacterium tuberculosis complex (mtbc). speculation surrounding this specificity has led to unsupported assertions in published studies and patents that nontuberculous mycobacteria (ntm) are wholly resistant to ds6a infection. in this study, we identified two independent nonessential regions in the ds6a genome and replaced them ...201627672191
non-tuberculous mycobacteria: classification, diagnostics, and therapy.non-tuberculous mycobacteria (ntm) are species other than those belonging to the mycobacterium tuberculosis complex and do not cause leprosy. ntm are generally free-living organisms that are ubiquitous in the environment. there have been more than 140 ntm species identified to-date. they can cause a wide range of infections, with pulmonary infections being the most frequent (65-90 %). there is growing evidence that the incidence of ntm lung diseases and associated hospitalizations are on the ris ...201627645543
mab_3551c encodes the primary triacylglycerol synthase involved in lipid accumulation in mycobacterium abscessus.slow growing pathogenic mycobacteria utilize host-derived lipids and accumulate large amounts of triacylglycerol (tag) in the form of intracytoplasmic lipid inclusions (ili), serving as a source of carbon and energy during prolonged infection. mycobacterium abscessus is an emerging and rapidly growing species capable to induce severe and chronic pulmonary infections. however, whether m. abscessus, like mycobacterium tuberculosis, possesses the machinery to acquire and store host lipids, remains ...201627513974
non-tuberculous mycobacteria: classification, diagnostics, and therapy.non-tuberculous mycobacteria (ntm) are species other than those belonging to the mycobacterium tuberculosis complex and do not cause leprosy. ntm are generally free-living organisms that are ubiquitous in the environment. there have been more than 140 ntm species identified to-date. they can cause a wide range of infections, with pulmonary infections being the most frequent (65-90 %). there is growing evidence that the incidence of ntm lung diseases and associated hospitalizations are on the ris ...201627401079
the impact of protein extraction protocols on the performance of currently available maldi-tof mass spectrometry for identification of mycobacterial clinical isolates cultured in liquid media.protein extraction step is particularly important for identification of mycobacterial isolates by maldi-tof mass spectrometry (ms) because of its thick and solid cell wall. this study compared the performance of maldi-tof ms for identification of mycobacterial clinical isolates cultured in liquid media between heating-based protocol and non-heating protocol.201627380997
whole-genome sequencing and comparative analysis of mycobacterium brisbanense reveals a possible soil origin and capability in fertiliser synthesis.mycobacterium brisbanense is a member of mycobacterium fortuitum third biovariant complex, which includes rapidly growing mycobacterium spp. that normally inhabit soil, dust and water, and can sometimes cause respiratory tract infections in humans. we present the first whole-genome analysis of m. brisbanense um_wwy which was isolated from a 70-year-old malaysian patient. molecular phylogenetic analyses confirmed the identification of this strain as m. brisbanense and showed that it has an unusua ...201627031249
analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis.the epistem genedrive assay rapidly detects the mycobacterium tuberculosis omplex from sputum and is currently available for clinical use. however, the analytical and clinical performance of this test has not been fully evaluated. the analytical limit of detection (lod) of the genedrive pcr amplification was tested with genomic dna; the performance of the complete (sample processing plus amplification) system was tested by spiking m. tuberculosismc(2)6030 cells into distilled water andm. tubercu ...201626865685
a chlorhexidine- agar plate culture medium protocol to complement standard broth culture of mycobacterium tuberculosis.the culture of mycobacterium tuberculosis using parallel inoculation of a solid culture medium and a liquid broth provides the gold standard for the diagnosis of tuberculosis. here, we evaluated a chlorhexidine decontamination-mod9 solid medium protocol versus the standard nalc-naoh-bactec 960 mgit protocol for the diagnosis of pulmonary tuberculosis by culture. three-hundred clinical specimens comprising 193 sputa, 30 bronchial aspirates, 10 broncho-alveolar lavages, 47 stools, and 20 urines we ...201626834733
listeria ivanovii infection in mice: restricted to the liver and lung with limited replication in the spleen.listeria monocytogenes (lm) vectors have shown much promise in delivery of viral and tumor antigens for the development of vaccines. l. ivanovii (li) is a closely related bacterium with a similar intracellular life cycle that may offer advantages over lm because it is not a human pathogen, but can infect other animal species. recent studies show that recombinant li expressing mycobacterium tuberculosis antigens is effective in inducing protective immunity in mouse models, demonstrating the poten ...201627375558
structure-guided, target-based drug discovery - exploiting genome information from hiv to mycobacterial infections.the use of protein crystallography in structure-guided drug discovery allows identification of potential inhibitor-binding sites and optimisation of interactions of hits and lead compounds with a target protein. an early example of this approach was the use of the structure of hiv protease in designing aids antivirals. more recently, use of structure-guided design with fragment-based drug discovery, which reduces the size of screening libraries by decreasing complexity, has improved ligand effic ...201628132480
trfa1 gene in clinical isolates of mycobacterium tuberculosis.the incidence of resistant strains of mycobacterium tuberculosis (mtb), including multi-drug resistant, extensively drug resistant, or totally drug resistant, is one of the major problems of health policies worldwide. the accumulation of mutations causes multi-drug resistant strains. mycobacterium abscessus has a plasmid called pmab2401 containing the trfa1 gene in its integron part. the aim of the present study was to investigate the possible existence of the trfa1 gene in clinical strains of m ...201628043564
identification of nontuberculous mycobacteria by high-performance liquid chromatography from patients in tehran.the genus mycobacterium contains over 140 species comprises pathogenic and nonpathogenic strains. nontuberculous mycobacteria (ntm) causing clinical disease have become increasingly common and more diverse. widespread features of ntm infection can make the diagnosis difficult. precise species-level detection can aid in distinguishing environmental contamination from actual infection and, furthermore, can assist in making a choice of antimicrobial therapy.201628043562
antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis.nontuberculous mycobacteria are mycobacteria, other than those in the mycobacterium tuberculosis complex, and are commonly found in the environment. nontuberculous mycobacteria species (most commonly mycobacterium avium complex and mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circu ...201628000919
prevalence and species spectrum of both pulmonary and extrapulmonary nontuberculous mycobacteria isolates at a tertiary care center.nontuberculous mycobacteria (ntm) infection associated with pulmonary and extrapulmonary disease has been increasing globally. despite an increase in incidence rate of ntm infection, its prevalence, species diversity, and circulation pattern in india is largely unknown. this study sought to investigate the overall burden and diversity of ntm among both pulmonary and extrapulmonary clinical isolates from a northern indian population.201627847012
mycobacterium bovis and other uncommon members of the mycobacterium tuberculosis complex.since its discovery by theobald smith, mycobacterium bovis has been a human pathogen closely related to animal disease. at present, m. bovis tuberculosis is still a problem of importance in many countries and is considered the main cause of zoonotic tuberculosis throughout the world. recent development of molecular epidemiological tools has helped us to improve our knowledge about transmission patterns of this organism, which causes a disease indistinguishable from that caused by mycobacterium t ...201628084202
association of slow recovery of mycobacterium africanum-infected patients posttreatment with high content of persister-like bacilli in pretreatment sputum.mycobacterium africanum that causes 40% of tuberculosis (tb) in west africa grows more slowly in culture and has similar transmission capacity compared with mycobacterium tuberculosis, but m. africanum-exposed contacts progress more slowly to active disease. the presence of lipid body (lb) containing m. tuberculosis complex (mtbc) cells in sputum samples has been associated with mycobacterial transcriptomes indicating slow or no growth and persister-like antibiotic tolerance. slow-growing bacill ...201628043641
the first population structure and comparative genomics analysis of mycobacterium africanum strains from ghana reveals higher diversity of lineage 5.mycobacterium africanum (maf) remains an important tb causing pathogen in west africa; however, little is known about its population structure and actual diversity which may have implications for diagnostics and vaccines. we carried out comparative genomics analysis of candidate mycobacterium tuberculosis (mtb) and maf using whole genome sequencing.201628043631
performance comparison of a pair of lowenstein-jensen media supplemented with pyruvate or glycerol, and the combination of both supplements in a single lowenstein-jensen medium for the growth support of the mycobacterium tuberculosis complex.to evaluate the performance of lowenstein-jensen medium (lj) supplemented with pyruvate and glycerol (ljpg), compared with lj supplemented with pyruvate (ljp) or glycerol (ljg) for the support of mycobacterial growth.201628043533
evaluation of the kudoh method for mycobacterial culture: gambia experience.to evaluate the kudoh swab method for improving laboratory diagnosis of tuberculosis (tb) in gambia.201628043531
type i interferon is pathogenic during chronic mycobacterium africanum infection.type i interferons (ifns, including ifn-αβ) contribute to the pathogenesis of mycobacterium tuberculosis strains that induce high ifn-αβ levels. in the current study we examined the role of ifn-αβ during infection with a mycobacterium africanum strain that induces low ifn-β levels. we infected wild-type and ifn-αβ receptor knockout mice with m. africanum and monitored bacterial growth, lung disease, and survival over 292 days. we found reduced lung bacterial burdens and less severe histopatholog ...201627803172
detection and characterization of drug-resistant conferring genes in mycobacterium tuberculosis complex strains: a prospective study in two distant regions of ghana.we spoligotyped and screened 1490 clinical mycobacterium tuberculosis complex strains from northern and greater accra regions of ghana against inh and rif using the microplate alamar blue phenotypic assay. specific drug resistance associated genetic elements of drug resistant strains were analyzed for mutations. a total of 111 (7.5%), 10 (0.7%) and 40 (2.6%) were mono-resistant to inh, rif, and mdr, respectively. we found the ghana spoligotype to be associated with drug resistance (inh: 22.1%; p ...201627450017
impact of the mycobaterium africanum west africa 2 lineage on tb diagnostics in west africa: decreased sensitivity of rapid identification tests in the gambia.mpt64 rapid speciation tests are increasingly being used in diagnosis of tuberculosis (tb). mycobacterium africanum west africa 2 (maf 2) remains an important cause of tb in west africa and causes one third of disease in the gambia. since the introduction of mpt64 antigen tests, a higher than expected rate of suspected non-tuberculous mycobacteria (ntm) was seen among afb smear positive tb suspects, which led us to prospectively assess sensitivity of the mpt64 antigen test in our setting.201627387550
draft genome sequence of a mycobacterium africanum clinical isolate from antioquia, colombia.mycobacterium africanum is a member of the mycobacterium tuberculosis complex. most commonly found in west african countries, it has scarcely been described in south america. here, we report the first genome sequence of a colombian m. africanum clinical isolate. it is composed of 4,493,502 bp, with 4,069 genes.201627257203
host immune responses differ between m. africanum- and m. tuberculosis-infected patients following standard anti-tuberculosis treatment.epidemiological differences exist between mycobacterium africanum (maf)- and mycobacterium tuberculosis (mtb)-infected patients, but to date, contributing host factors have not been characterised. we analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and esat6/cfp-10-, whole-maf- and mtb-stimulated blood samples of 26 maf- and 49 mtb-hiv-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. before treatment ...201627192147
c-reactive protein, neopterin and beta2 microglobulin levels pre and post tb treatment in the gambia.tuberculosis is one of the leading causes of morbidity and mortality in developing countries. analysis of the host immune response may help with generating point-of-care tests for personalised monitoring. thus, the aim of this study was to assess the relationship between immune activation markers: c-reactive protein (crp), beta2 microglobulin (b2m) and neopterin, disease severity prior to treatment and response to therapy in adult pulmonary tb patients.201626951717
whole genome sequencing of mycobacterium africanum strains from mali provides insights into the mechanisms of geographic restriction.mycobacterium africanum, made up of lineages 5 and 6 within the mycobacterium tuberculosis complex (mtc), causes up to half of all tuberculosis cases in west africa, but is rarely found outside of this region. the reasons for this geographical restriction remain unknown. possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of west african ethnicity, and an inability to compete with other lineages outside of west africa. these latter two hypotheses ...201626751217
mechanistic insight into mycobacterial mmpl protein function.mycobacterial cell walls are complex structures containing a broad range of unusual lipids, glycolipids and other polymers, some of which act as immunomodulators or virulence determinants. better understanding of the enzymes involved in export processes would enlighten cell wall biogenesis. bernut et al. () present the findings of a structural and functional investigation of one of the most important transporter families, the mmpl proteins, members of the resistance-nodulation-cell division (rnd ...201626710752
insights into the smooth-to-rough transitioning in mycobacterium bolletii unravels a functional tyr residue conserved in all mycobacterial mmpl family members.in mycobacteria, mmpl proteins represent key components that participate in the biosynthesis of the complex cell envelope. whole genome analysis of a spontaneous rough morphotype variant of mycobacterium abscessus subsp. bolletii identified a conserved tyrosine that is crucial for the function of mmpl family proteins. isogenic smooth (s) and rough (r) variants differed by a single mutation linked to a y842h substitution in mmpl4a. this mutation caused a deficiency in glycopeptidolipid production ...201626585558
rapid identification of mycobacterium avium ssp paratuberculosis laboratory strains by is900-nested polymerase chain reaction.mycobacterium avium ssp paratuberculosis (map) causes paratuberculosis (johne's disease) in ruminants. as a species, m. avium comprises m. avium subsp. hominissuis and a number of clones that are known to have evolved from this subspecies, namely m. avium subsp. avium (maa), m. avium subsp. silvaticum, and map. despite the very high genomic similarity of map and maa, the insertion sequence is900, which is 1,451-bp long, is now understood to be exclusively present in 10-20 copies in the genome of ...201628043575
deciphering the virulence factors of the opportunistic pathogen mycobacterium colombiense.mycobacterium avium complex (mac) contains clinically important nontuberculous mycobacteria worldwide and is the second largest medical complex in the mycobacterium genus after the mycobacterium tuberculosis complex. mac comprises several species that are closely phylogenetically related but diverse regarding their host preference, course of disease, virulence and immune response. in this study we provided immunologic and virulence-related insights into the m. colombiense genome as a model of an ...201627818776
[identification of mycobacteria isolated from aids patients].obstract: to identify mycobacteria isolated from aids patients and to evaluate the diagnostic value of mbp64 antigen colloidal gold diagnostic kit in distinguishing mycobacterium tuberculosis(mtb) and nontuberculous mycobacteria (ntm). methods: a total of 140 mycobacteria isolates from aids patients were collected and identified by using 16srdna pcr assay as well as immune colloidal gold technique (mbp64 antigen colloidal gold diagnostic kit). the sensitivity and specificity of colloidal gold me ...201627677657
[identification of mycobacteria isolated from aids patients].obstract: to identify mycobacteria isolated from aids patients and to evaluate the diagnostic value of mbp64 antigen colloidal gold diagnostic kit in distinguishing mycobacterium tuberculosis(mtb) and nontuberculous mycobacteria (ntm).201627651187
in vitro activity of 3-triazeneindoles against mycobacterium tuberculosis and mycobacterium avium.among 230 target-synthesized indole-based compounds, seven 3-triazenoindoles showed mics of 0.2 to 0.5 μg/ml against mycobacterium tuberculosis strain h37rv and isoniazid-resistant human isolate cn-40. the tu112 compound was active also against a dormant form of m. tuberculosis some of these triazenoindoles were active against mycobacterium avium, with mics of 0.05 to 0.5 μg/ml. the selectivity indices (si) for m. tuberculosis and m. avium were significantly higher than 10, making these compound ...201627503657
preparation, standardization and in vitro safety testing of mycobacterium nosodes (emtact- polyvalent nosode).most of the nosodes in the homeopathic pharmacopeia have been sourced from obscure pathological material over a century ago; of which no scientific documentation is available.201627473543
comparative genomics and proteomic analysis of four non-tuberculous mycobacterium species and mycobacterium tuberculosis complex: occurrence of shared immunogenic proteins.the esx and pe/ppe families of proteins are among the most immunodominant mycobacterial antigens and have thus been the focus of research to develop vaccines and immunological tests for diagnosis of bovine and human tuberculosis, mainly caused by mycobacterium bovis and mycobacterium tuberculosis, respectively. in non-tuberculous mycobacteria (ntm), multiple copies of genes encoding homologous proteins have mainly been identified in pathogenic mycobacterium species phylogenically related to myco ...201627375559
synthesis and evaluation of antitubercular activity of fluorinated 5-aryl-4-(hetero)aryl substituted pyrimidines.various 5-(fluoroaryl)-4-(hetero)aryl substituted pyrimidines have been synthesized based on the suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (sn(h)) reactions starting from commercially available 5-bromopyrimidine and their antitubercular activity against mycobacterium tuberculosis h37rv has been explored. the outcome of the study disclose that, some of the compounds have showed promising activity in micromolar concentration against mycobacterium tuberculosis h37rv, ...201627338658
the mechanism of cytoskeleton protein β-actin and cofilin-1 of macrophages infected by mycobacterium avium.cytoskeleton proteins and their regulation proteins could be influenced seriously in mycobacterium tuberculosis infection host cells leading to the apoptosis of host cells. macrophages infected by mycobacterium avium were detected from cell morphology and genome levels to analyze changes of the cytoskeleton of m. avium infection macrophages. then the expression of β-actin, cofilin-1 proteins in m. avium infected macrophages were analyzed by western blotting, and the apoptosis of m. avium infecti ...201627158391
inverse correlation between salt tolerance and host-adaptation in mycobacteria.the genus mycobacterium includes host-adapted organisms regarded as obligate and opportunistic pathogens and environmental organisms. factors contributing to this wide range of adaptations are poorly known.201627129386
synthesis and antimycobacterial activity of n-(2-aminopurin-6-yl) and n-(purin-6-yl) amino acids and dipeptides.synthetic routes to novel n-(purin-6-yl)- and n-(2-aminopurin-6-yl) conjugates with amino acids and glycine-containing dipeptides were developed. in vitro testing of 42 new and known compounds made it possible to reveal a series of n-(purin-6-yl)- and n-(2-aminopurin-6-yl) conjugates exhibiting significant antimycobacterial activity against mycobacterium tuberculosis h37rv, mycobacterium avium, mycobacterium terrae, and multidrug-resistant m. tuberculosis strain isolated from tuberculosis patien ...201627107949
[establishment of multiplex pcr method for rapid detection of nontuberculous mycobacteriums infection in the hand].to establish a multiplex polymerase chain reaction (mpcr) method with high sensitivity and specificity for rapid detection of common nontuberculous mycobacterium(ntm) infection in the hand.201627095780
validation of a multiplex real-time pcr assay for detection of mycobacterium spp., mycobacterium tuberculosis complex, and mycobacterium avium complex directly from clinical samples by use of the bd max open system.a multiplex real-time pcr was validated on the bd max open system to detect different mycobacterium tuberculosis complex, mycobacterium avium complex, and mycobacterium spp. directly from clinical samples. the pcr results were compared to those with traditional cultures. the multiplex pcr assay was found to be a specific and sensitive method for the rapid detection of mycobacteria directly from clinical specimens.201627008873
lady windermere syndrome: a very rare entity in indian medical scenario.bronchiectasis is a common respiratory disorder, which we come across in clinical practice. patients with bronchiectasis are prone to infections, especially of mycobacterium tuberculosis. however, non-tubercular mycobacterial infections may also set in, though rare. here, we report an unusual case of mycobacterium avium complex infection in a case of middle lobe bronchiectasis that was seen in a middle-aged immunocompetent female, a syndrome known as lady windermere syndrome.201626894109
nlpc/p60 domain-containing proteins of mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan.a subset of proteins containing nlpc/p60 domains are bacterial peptidoglycan hydrolases that cleave noncanonical peptide linkages and contribute to cell wall remodeling as well as cell separation during late stages of division. some of these proteins have been shown to cleave peptidoglycan in mycobacterium tuberculosis and play a role in mycobacterium marinum virulence of zebra fish; however, there are still significant knowledge gaps concerning the molecular function of these proteins in mycoba ...201626799947
discovery of allosteric and selective inhibitors of inorganic pyrophosphatase from mycobacterium tuberculosis.inorganic pyrophosphatase (ppiase) is an essential enzyme that hydrolyzes inorganic pyrophosphate (ppi), driving numerous metabolic processes. we report a discovery of an allosteric inhibitor (2,4-bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-s-triazine) of bacterial ppiases. analogues of this lead compound were synthesized to target specifically mycobacterium tuberculosis (mtb) ppiase (mtppiase). the best analogue (compound 16) with a ki of 11 μm for mtppiase is a species-specific inhibitor. cryst ...201627622287
mycobacterium tuberculosis zinc metalloprotease-1 assists mycobacterial dissemination in zebrafish.zinc metalloprotease-1 (zmp1) from mycobacterium tuberculosis (m.tb), the tuberculosis (tb) causing bacillus, is a virulence factor involved in inflammasome inactivation and phagosome maturation arrest. we earlier reported that zmp1 was secreted under granuloma-like stress conditions, induced th2 cytokine microenvironment and was highly immunogenic in tb patients as evident from high anti-zmp1 antibody titers in their sera. in this study, we deciphered a new physiological role of zmp1 in mycobac ...201627621726
executive summary: official american thoracic society/centers for disease control and prevention/infectious diseases society of america clinical practice guidelines: treatment of drug-susceptible tuberculosis.the american thoracic society, centers for disease control and prevention, and infectious diseases society of america jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the european respiratory society and the us national tuberculosis controllers association. representatives from the american academy of pediatrics, the canadian thoracic society, the international union against tuberculosis and lung disease, and the wo ...201627621353
delamanid susceptibility testing of mycobacterium tuberculosis using the resazurin microtitre assay and the bactec™ mgit™ 960 system-authors' response. 201627621178
bioinformatics identification of drug resistance-associated gene pairs in mycobacterium tuberculosis.tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis (mtb). due to the extensive use of anti-tuberculosis drugs and the development of mutations, the emergence and spread of multidrug-resistant tuberculosis is recognized as one of the most dangerous threats to global tuberculosis control. some single mutations have been identified to be significantly linked with drug resistance. however, the prior research did not take gene-gene interactions into account, and the eme ...201627618895
stereocontrolled total synthesis of muraymycin d1 having a dual mode of action against mycobacterium tuberculosis.a stereocontrolled first total synthesis of muraymycin d1 (1) has been achieved. the synthetic route is highly stereoselective, featuring (1) selective β-ribosylation of the c2-methylated amino ribose, (2) selective strecker reaction, and (3) ring-opening reaction of a diastereomeric mixture of a diaminolactone to synthesize muraymycidine (epi-capreomycidine). the acid-cleavable protecting groups for secondary alcohol and uridine ureido nitrogen are applied for simultaneous deprotections with th ...201627617631
mycobacterium tuberculosis exploits the formation of new blood vessels for its dissemination.the mechanisms by which the airborne pathogen mycobacterium tuberculosis spreads within the lung and leaves its primary niche to colonize other organs, thus inducing extrapulmonary forms of tuberculosis (tb) in humans, remains poorly understood. herein, we used a transcriptomic approach to investigate the host cell gene expression profile in m. tuberculosis-infected human macrophages (μφ). we identified 33 genes, encoding proteins involved in angiogenesis, for which the expression was significan ...201627616470
tracing mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in east greenland.in east greenland, a dramatic increase of tuberculosis (tb) incidence has been observed in recent years. classical genotyping suggests a genetically similar mycobacterium tuberculosis (mtb) strain population as cause, however, precise transmission patterns are unclear. we performed whole genome sequencing (wgs) of mtb isolates from 98% of culture-positive tb cases through 21 years (n = 182) which revealed four genomic clusters of the euro-american lineage (mainly sub-lineage 4.8 (n = 134)). the ...201627615360
elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents.we report the design and synthesis of a series of non-nucleoside mtbtmpk inhibitors (1-14) based on the gram-positive bacterial tmpk inhibitor hit compound 1. a practical synthesis was developed to access these analogues. several compounds show promising mtbtmpk inhibitory potency and allow the establishment of a structure-activity relationship, which is helpful for further optimization.201627614917
anti-inflammatory, antioxidant and anti-mycobacterium tuberculosis activity of viridiflorol: the major constituent of allophylus edulis (a. st.-hil., a. juss. & cambess.) radlk.the leaves of allophylus edulis (a. st.-hil., a. juss. & cambess.) radlk. (sapindaceae) are traditionally used as a natural anti-inflammatory agent; however, there are no scientific studies demonstrating its activity essential oil. the content of essential oil in a. edulis may be the chemical basis to explain its ethnobotanical uses, since infusions of this plant are used to treat inflammation in the traditional medicine in brazil.201627612433
overview on mechanisms of isoniazid action and resistance in mycobacterium tuberculosis.isoniazid (inh) is one of the most active compounds used to treat tuberculosis (tb) worldwide. in addition, inh has been used as a prophylactic drug for individuals with latent mycobacterium tuberculosis (mtb) infection to prevent reactivation of disease. importantly, the definition of multidrug resistance (mdr) in tb is based on the resistance of mtb strains to inh and rifampicin (rif). despite its simple chemical structure, the mechanism of action of inh is very complex and involves several di ...201627612406
tuberculosis tenosynovitis with multiple rice bodies of the flexor tendons in the wrist: a case report.one of the infectious causes of wrist tenosynovitis is mycobacterium tuberculosis. tendon sheath involvement is rare. herein, we report the diagnosis and treatment of a patient with neglected wrist flexor tendon sheath tuberculosis.201627611797
[sapm-induced fusion blocking of autophagosome-lysosome is depended on interaction with rab7].objective to study the role of rab7 in the blockage of autophagosome-lysosome fusion induced by secretory acid phosphatase (sapm), a virulence factor of mycobacterium tuberculosis. methods the raw264.7 cells were transfected with sirab7, and the p62 was detected using western blotting. after transfected with mcherry-sapm, the co-localization of sapm and rab7 in raw264.7 cells was detected by immunofluorescence cytochemistry and the interaction of sapm with rab7 was determined by co-immunoprecipi ...201627609571
exploring intein inhibition by platinum compounds as an antimicrobial strategy.inteins, self-splicing protein elements, interrupt genes and proteins in many microbes, including the human pathogen mycobacterium tuberculosis using conserved catalytic nucleophiles at their n- and c-terminal splice junctions, inteins are able to excise out of precursor polypeptides. the splicing of the intein in the mycobacterial recombinase reca is specifically inhibited by the widely used cancer therapeutic cisplatin, cis-[pt(nh3)2cl2], and this compound inhibits mycobacterial growth. mass s ...201627609519
the mimic epitopes of mycobacterium tuberculosis screened by phage display peptide library have serodiagnostic potential for tuberculosis.mycobacterium tuberculosis is an obligate pathogenic bacterial species in the family of mycobacteriaceae and attracts excessive immune responses which cause pathology of the lungs in active tuberculosis. the lack of more sensitive and effective diagnosis reagents advocates a further recognition for the fast diagnostic and immunological measures for tuberculosis. here, two 12-mer peptides with core sequences of svsvgmkpsprp (cs1) and tmgftaprfphy (cs2) were screened from a phage display random pe ...201627609463
microbiome changes during tuberculosis and antituberculous therapy.the critical role of commensal microbiota in the human body has been increasingly recognized, and our understanding of its implications in human health and disease has expanded rapidly. the lower respiratory tract contains diverse communities of microbes known as lung microbiota, which are present in healthy individuals and in individuals with respiratory diseases. the dysbiosis of the airway microbiota in pulmonary tuberculosis (tb) may play a role in the pathophysiological processes associated ...201627608937
oxygen availability and metabolic dynamics during mycobacterium tuberculosis latency.in vitro models of mycobacterium tuberculosis (mtb) nonreplicating persistence (nrp) suggest the rate of oxygen ( o2 ) depletion is a significant determinant in persistence. however, few studies have characterized the metabolic association between slow and rapid o2 depletion rates and successful versus failed persistence.201627608448
[hemophagocytic syndrome associated with tuberculosis in a patient with acquired immunodeficiency].the secondary hemophagocytic syndrome is rare in children and even rarer associated with tuberculosis. e report the case of a patient with acquired immunodeficiency syndrome, disseminated tuberculosis and hemophagocytic syndrome. an 8-year-old girl, diagnosed with acquired immunodeficiency syndrome, was admitted due to fever, vomiting and abdominal pain. she presented abdominal distension, dehydration, tachypnea, crackles and wheezing in both lungs, anemia, thrombocytopenia and coagulopathy. she ...201627606663
in vivo mycobacterium tuberculosis fluoroquinolone resistance emergence: a complex phenomenon poorly detected by current diagnostic tests.heteroresistance, described both in terms of various point mutations resulting in different levels of resistance and in terms of a mixture of mutant and wt bacilli, is identified in up to one-third of fluoroquinolone (fq)-resistant mycobacterium tuberculosis isolates. heteroresistance is a challenge for current phenotypic and genotypic susceptibility testing (dst) regimes. we aimed to compare the performances of different phenotypic and genotypic dst in the context of fq heteroresistance by mimi ...201627605600
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