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antimycobacterial and herbicidal activity of ring-substituted 1-hydroxynaphthalene-2-carboxanilides.in this study, a series of 22 ring-substituted 1-hydroxynaphthalene-2-carboxanilides were prepared and characterized. primary in vitro screening of the synthesized compounds was performed against mycobacterium marinum, mycobacterium kansasii and mycobacterium smegmatis. the compounds were also tested for their activity related to inhibition of photosynthetic electron transport (pet) in spinach (spinacia oleracea l.) chloroplasts. most of tested compounds showed the antimycobacterial activity aga ...201324075143
antimycobacterial efficacy of silver nanoparticles as deposited on porous membrane filters.environmental mycobacteria pose a significant health burden. non-tuberculous mycobacteria infections have been traced to water treatment networks, where mycobacterial biofilms are ubiquitous. filters that remove potential pathogens have significant medical applications. the purpose of this study is to demonstrate that an antibacterial silver nanoparticle (agnp) coating can prevent colonization and growth of a mycobacterial biofilm on a filter material. the antibacterial efficacy of commercially ...201324094162
revealing of mycobacterium marinum transcriptome by rna-seq.transcriptome analysis has played an essential role for revealing gene expression and the complexity of regulations at transcriptional level. rna-seq is a powerful tool for transcriptome profiling, which uses deep-sequencing technologies to directly determine the cdna sequence. here, we utilized rna-seq to explore the transcriptome of mycobacteriummarinum (m. marinum), which is a useful model to study the pathogenesis of mycobacterium tuberculosis (mtb). two profiles of exponential and early sta ...201324098731
microrna-146 function in the innate immune transcriptome response of zebrafish embryos to salmonella typhimurium infection.micrornas (mirnas) have recently been shown to play important roles in development of the immune system and in fine-tuning of immune responses. human mir-146 family members are known as inflammation-inducible mirnas involved in negative feedback regulation of toll-like receptor (tlr) signalling. dysregulation of the mir-146 family has often been linked to inflammatory diseases and malignancies. this study reports on mir-146a and mir-146b as infection-inducible mirnas in zebrafish, which has emer ...201324112639
analysis of seca2-dependent substrates in mycobacterium marinum identifies protein kinase g (pkng) as a virulence effector.the pathogenicity of mycobacteria is closely associated with their ability to export virulence factors. for this purpose, mycobacteria possess different protein secretion systems, including the accessory sec translocation pathway, seca2. although this pathway is associated with intracellular survival and virulence, the seca2-dependent effector proteins remain largely undefined. in this work, we studied a mycobacterium marinum seca2 mutant with an impaired capacity to initiate granuloma formation ...201424119166
rapid detection and identification of nontuberculous mycobacterial pathogens in fish by using high-resolution melting analysis.mycobacterial infections in fish are commonly referred to as piscine mycobacteriosis, irrespectively of the specific identity of the causal organism. they usually cause a chronic disease and sometimes may result in high mortalities and severe economic losses. nearly 20 species of mycobacterium have been reported to infect fish. among them, mycobacterium marinum, m. fortuitum, and m. chelonae are generally considered the major agents responsible for fish mycobacteriosis. as no quick and inexpensi ...201324123734
paramecium caudatum enhances transmission and infectivity of mycobacterium marinum and m. chelonae in zebrafish danio rerio.mycobacterial infections in laboratory zebrafish danio rerio are common and widespread in research colonies. mycobacteria within free-living amoebae have been shown to be transmission vectors for mycobacteriosis. paramecium caudatum are commonly used as a first food for zebrafish, and we investigated this ciliate's potential to serve as a vector of mycobacterium marinum and m. chelonae. the ability of live p. caudatum to transmit these mycobacteria to larval, juvenile and adult zebrafish was eva ...201324192000
masquerading mycobacterium: plastic surgeon to the rescue.a patient with a mycobacterium marinum infection of the hand is described. the present case illustrates that m marinum infection may mimic common skin conditions such as eczema, and fungal and parasitic infestations. key elements in the diagnosis and management of this infection are a high index of suspicion, a detailed history of recreational or occupational exposure to exotic fish, tissue biopsy, wound culture and prompt empirical antibiotic therapy. once in vitro organism sensitivities are ob ...200524223001
increased phagocytosis of mycobacterium marinum mutants defective in lipooligosaccharide production: a structure-activity relationship study.mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in ectotherms and is an occasional opportunistic human pathogen. in the environment, m. marinum also interacts with amoebae, which may serve as a natural reservoir for this microorganism. however, the description of mycobacterial determinants in the early interaction with macrophages or amoebae remains elusive. lipooligosaccharides (loss) are cell surface-exposed glycolipids capable of modulating the host ...201424235141
mycobacterium marinum infection from sea monkeys.a case of cutaneous mycobacterium marinum infection acquired from artemia nyos (sea monkeys) is presented. the infection was unresponsive to initial antimicrobial therapies. a biopsy of a lesion revealed granulomatous inflammation with cultures that subsequently grew m marinum. a three-month course of clarithromycin provided complete resolution.201224294280
mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.the evolutionary survival of mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. at its initial peripheral infection site in the distal lung airways, m. tuberculosis infects macrophages, which transport it to deeper tissues. how mycobacteria survive in these broadly microbicidal cells is an important question. here we show in mice and zebrafish that m. tuberculosis, and its close pathogenic relative mycobacter ...201424336213
hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism.tuberculosis is a current major world-health problem, exacerbated by the causative pathogen, mycobacterium tuberculosis (mtb), becoming increasingly resistant to conventional antibiotic treatment. mtb is able to counteract the bactericidal mechanisms of leukocytes to survive intracellularly and develop a niche permissive for proliferation and dissemination. understanding of the pathogenesis of mycobacterial infections such as tuberculosis (tb) remains limited, especially for early infection and ...201324367256
atypical mycobacterium marinum infection (aquarium granuloma) in a patient on tnfα antagonist therapy for psoriatic arthritis. 201424387972
fish tank granuloma caused by mycobacterium marinum in two aquarists: two case reports.mycobacterium marinum, the cause of chronic systemic infections in fish, occasionally causes granulomatous skin and soft tissue lesions in humans. cutaneous mycobacterial infection in two patients owing to unusual circumstances is presented in this report. the first patient was infected through improper hygienic behavior, while infection in the second patient was previously misdiagnosed as rheumatoid arthritis and treated with methylprednisolone for a period of three months, which resulted in a ...201324392446
human pathogenic bacteria, fungi, and viruses in drosophila: disease modeling, lessons, and shortcomings.drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. many drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. we discuss studies of human pathogens in flies revealing not only ...201424398387
identification and functional characterization of the goldfish (carassius auratus l.) high mobility group box 1 (hmgb1) chromatin-binding protein.we report on the identification and functional characterization of hmgb1 of the goldfish. quantitative analysis indicated the highest expression of goldfish hmgb1 in the brain, with lower mrna levels in spleen, intestine, kidney, gill and heart. hmgb1 was also differentially expressed in goldfish immune cell populations with highest mrna levels present in splenocytes and neutrophils. we generated and functionally characterized the recombinant hmgb1 (rghmgb1). the rghmgb1 primed the respiratory b ...201424406304
recurrent cutaneous abscesses in two italian family members.environmental mycobacteria are the causative factors of an increasing number of infections worldwide. cutaneous infections as a result of such mycobacteria are often misdiagnosed, and their treatment is difficult since they can show in vivo and in vitro multidrug resistance. absence of pathognomonic clinical signs and variable histological findings often delay diagnosis. we report a case of localized recurrent soft tissue swelling by mycobacterium marinum in 2 members of the same family. the cas ...201024470891
asymmetric cell division in mycobacterium tuberculosis and its unique features.recently, several reports showed that about 80 % of mid-log phase mycobacterium smegmatis, mycobacterium marinum, and mycobacterium bovis bcg cells divide symmetrically with 5-10 % deviation in the septum position from the median. however, the mode of cell division of the pathogenic mycobacterial species, mycobacterium tuberculosis, remained unclear. therefore, in the present study, using electron microscopy, fluorescence microscopy of septum- and nucleoid-stained live and fixed cells, and live ...201424481536
establishment and validation of whole-cell based fluorescence assays to identify anti-mycobacterial compounds using the acanthamoeba castellanii-mycobacterium marinum host-pathogen system.tuberculosis is considered to be one of the world's deadliest disease with 2 million deaths each year. the need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. despite multiple recent efforts, the majority of the hits discovered by traditional target-based screening showed low efficiency in vivo. therefore, there is heightened demand for whole-cell based approaches directly using host-pathogen systems. the phenotypic host-pathogen assay described ...201424498207
treatment of biopsy and culture negative mycobacterium marinum: diagnostic and therapeutic considerations.mycobacterium marinum infections are frequently linked to aquatic environments. cutaneous infections with these organisms cause superficial nodules, ulcerations, and pustules on the skin. involvement of the deeper tissue may occur when diagnosis and treatment are delayed, allowing the organisms to spread. the diagnostic criteria for infections rely on a detailed patient history, a typical clinical presentation, positive cultures, characteristic organism smear, and if available cr-rflp analysis a ...201424509973
mycobacterium marinum infection following contact with reptiles: vivarium granuloma.a 19-year-old man presented with a 1.5-cm nodule on the first dorsal metacarpal ray. the patient denied having contact with fish tanks or fish, but recalled handling many reptiles without gloves in the vivarium where he worked. a culture of a skin biopsy specimen yielded mycobacterium marinum. the clinical outcome was favourable after a 2-week course of intramuscular gentamicin (180 mg daily) combined with a 6-week course of oral clarithromycin (500 mg twice a day). doctors should be aware that ...201424530276
atypical mycobacterial cutaneous infections in egyptians: a clinicopathological study.atypical mycobacteria comprise an uncommon heterogenous non-tuberculous group of acid-fast bacteria that rarely involve skin. the pattern of atypical mycobacterial cutaneous infections (amci) has not been previously studied in egypt. the aim of this study was to describe the clinical characteristics, pathological features and species profile of amci among egyptian patients. a retrospective study included 46 cases, diagnosed with amci during the period 2002 to 2012. the study included 34 males (7 ...201424533920
bacterial infections from aquatic species: potential for and prevention of contact zoonoses.as aquaculture production and the consumption of aquaculture products increase, the possibility of contracting zoonotic infections from either handling or ingesting these products also increases. the principal pathogens acquired topically from fish or shellfish through spine/pincer puncture or open wounds are aeromonas hydrophila, edwardsiella tarda, mycobacterium marinum, streptococcus iniae, vibrio vulnificus and v. damsela. these pathogens, which are all indigenous to the aquatic environment, ...201324547653
a novel esx-1 locus reveals that surface-associated esx-1 substrates mediate virulence in mycobacterium marinum.esxa (esat-6) and esxb (cfp-10) are virulence factors exported by the esx-1 system in mycobacterial pathogens. in mycobacterium marinum, an established model for esx-1 secretion in mycobacterium tuberculosis, genes required for esx-1 export reside at the extended region of difference 1 (rd1) locus. in this study, a novel locus required for esx-1 export in m. marinum was identified outside the rd1 locus. an m. marinum strain bearing a transposon-insertion between the mmar_1663 and mmar_1664 genes ...201424610712
review of mycobacterium marinum infection reported from iran and report of three new cases with sporotrichoid presentation.mycobacterium marinum infection is the most common nontuberculous mycobacterial skin lesions. it results from skin injury and contact with contaminated water, fish, or shellfish; its infections have low frequency, nonspecific symptoms and lack of specific identification methods that can alter correct diagnosis.this study designed about cases that reported from iran and comparing their presentation and clinical sign and symptom and outcome.201424719723
mycobacterium tuberculosis pili (mtp), a putative biomarker for a tuberculosis diagnostic test.novel biomarkers are urgently needed for point of care tb diagnostics. in this study, we investigated the potential of the pilin subunit protein encoded by the mtp gene as a diagnostic biomarker. blast analysis of the mtp gene on published genome databases, and amplicon sequencing were performed in mycobacterium tuberculosis complex (mtbc) strains and other organisms. the protein secondary structure of the amino acid sequences of non-tuberculous mycobacteria that partially aligned with the mtp s ...201424721207
capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry for top-down characterization of the mycobacterium marinum secretome.capillary zone electrophoresis (cze) with an electrokinetically pumped sheath-flow nanospray interface was coupled with a high-resolution q-exactive mass spectrometer for the analysis of culture filtrates from mycobacterium marinum. we confidently identified 22 gene products from the wildtype m. marinum secretome in a single cze-tandem mass spectrometry (ms/ms) run. a total of 58 proteoforms were observed with post-translational modifications including signal peptide removal, n-terminal methioni ...201424725189
rare diagnosis of nodular lymphangitis caused by mycobacterium marinum: mdct imaging findings.mycobacterium marinum is an atypical mycobacterium that usually causes a solitary nodule on the hand ("fish tank granuloma") or less commonly, secondary erythematous channels and nodules spread along lymphatic drainage of the extremity, mimicking sporothricoid skin lesions of nodular lymphangitis. this report presents a case of this rare entity, a nodular lymphangitis caused by mycobacterium marinum. multidetector computed tomography (mdct) imaging was very useful in determining the morphology ( ...201424778804
design, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives.in an effort to develop novel potent antitubercular drugs, thirty-one oridonin derivatives were designed and prepared. all the compounds obtained were screened for their in vitro activities against mycobacterium phlei, mycobacterium smegmatis and mycobacterium marinum. among them, thirteen compounds showed significant inhibitory activity against m. phlei with mics less than 2 μg/ml. compounds 2k, 8d, 10c, 10d containing trans-cinnamic acid moiety were the most potent (mic=0.5 μg/ml), comparable ...201424835198
whole genome analyses of marine fish pathogenic isolate, mycobacterium sp. 012931.mycobacterium is a genus within the order actinomycetales that comprises of a large number of well-characterized species, several of which includes pathogens known to cause serious disease in human and animal. here, we report the whole genome sequence of mycobacterium sp. strain 012931 isolated from the marine fish, yellowtail (seriola quinqueradiata). mycobacterium sp. 012931 is a fish pathogen causing serious damage to aquaculture farms in japan. dna dot plot analysis showed that mycobacterium ...201424879010
nanoparticles as drug delivery system against tuberculosis in zebrafish embryos: direct visualization and treatment.nanoparticles (nps) enclosing antibiotics have provided promising therapy against mycobacterium tuberculosis (mtb) in different mammalian models. however, the nps were not visualized in any of these animal studies. here, we introduce the transparent zebrafish embryo as a system for noninvasive, simultaneous imaging of fluorescent nps and the fish tuberculosis (tb) agent mycobacterium marinum (mm). the study was facilitated by the use of transgenic lines of macrophages, neutrophils, and endotheli ...201424945994
highly deviated asymmetric division in very low proportion of mycobacterial mid-log phase cells.in this study, we show that about 20% of the septating mycobacterium smegmatis and mycobacterium xenopi cells in the exponential phase populationdivideasymmetrically, with an unusually high deviation (17 ± 4%) in the division site from the median, to generate short cells and long cells, thereby generating population heterogeneity. this mode of division is very different from the symmetric division of themajority (about 80%) of the septating cells in the mycobacterium smegmatis, mycobacterium mar ...201424949109
flexor pollicis longus tenosynovitis caused by mycobacterium marinum infection. 201424957591
mycobacteria counteract a tlr-mediated nitrosative defense mechanism in a zebrafish infection model.pulmonary tuberculosis (tb), caused by the intracellular bacterial pathogen mycobacterium tuberculosis (mtb), is a major world health problem. the production of reactive nitrogen species (rns) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. nevertheless, the protective role of rns during mtb infection remains controversial. here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pat ...201424967596
adequate th2-type response associates with restricted bacterial growth in latent mycobacterial infection of zebrafish.tuberculosis is still a major health problem worldwide. currently it is not known what kind of immune responses lead to successful control and clearance of mycobacterium tuberculosis. this gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. we have used the mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immu ...201424968056
fit for consumption: zebrafish as a model for tuberculosis.despite efforts to generate new vaccines and antibiotics for tuberculosis, the disease remains a public health problem worldwide. the zebrafish danio rerio has emerged as a useful model to investigate mycobacterial pathogenesis and treatment. infection of zebrafish with mycobacterium marinum, the closest relative of the mycobacterium tuberculosis complex, recapitulates many aspects of human tuberculosis. the zebrafish model affords optical transparency, abundant genetic tools and in vivo imaging ...201424973748
modeling tuberculous meningitis in zebrafish using mycobacterium marinum.tuberculous meningitis (tbm) is one of the most severe extrapulmonary manifestations of tuberculosis, with a high morbidity and mortality. characteristic pathological features of tbm are rich foci, i.e. brain- and spinal-cord-specific granulomas formed after hematogenous spread of pulmonary tuberculosis. little is known about the early pathogenesis of tbm and the role of rich foci. we have adapted the zebrafish model of mycobacterium marinum infection (zebrafish-m. marinum model) to study tbm. f ...201424997190
a case of extensive cutaneous mycobacterium marinum infection in a pacific islander living in new zealand.mycobacterium marinum is a rare cause of cutaneous infection. the typical clinical picture consists of one or more discrete well circumscribed lesions affecting the upper limbs. however, a more exuberant form has been described in the south pacific, where it is sometimes entitled 'spam disease' given the infected skin's similar appearance to the canned food. we describe a case of this more extensive infection in a south pacific islander who appears to have acquired the infection in new zealand, ...201424997705
establishment and optimization of a high throughput setup to study staphylococcus epidermidis and mycobacterium marinum infection as a model for drug discovery.zebrafish are becoming a valuable tool in the preclinical phase of drug discovery screenings as a whole animal model with high throughput screening possibilities. they can be used to bridge the gap between cell based assays at earlier stages and in vivo validation in mammalian models, reducing, in this way, the number of compounds passing through to testing on the much more expensive rodent models. in this light, in the present manuscript is described a new high throughput pipeline using zebrafi ...201424998295
mycobacterium marinum infection in japanese forest green tree frogs (rhacophorus arboreus).four japanese forest green tree frogs (rhacophorus arboreus) were presented with emaciation, abdominal distention and ulcerative and nodular cutaneous lesions affecting the brisket, limbs, digits and ventral abdomen. another three frogs had been found dead in the same tank 1 year previously. necropsy examination of these seven frogs revealed splenomegaly and hepatomegaly, with multiple tan-yellow nodular foci present in the liver, spleen, heart, lungs, ovaries and kidneys. microscopically, five ...201425047922
emerging causes of superficial and invasive infections following marine injuries and exposures.soft tissue bacterial infections following aquatic animal bites, stings, and minor injuries occur commonly and usually on the extremities in fishermen and beachgoers worldwide after freshwater and saltwater exposures. louisiana has more tidal, saltwater, and brackish water shorelines (more than 7,000 miles) than any other state, including alaska and hawaii. as a result, louisiana residents are often exposed to marine pathogens when fishing or working offshore or when enjoying louisiana's miles o ...201725075726
phagocytosis of mycobacteria by zebrafish macrophages is dependent on the scavenger receptor marco, a key control factor of pro-inflammatory signalling.scavenger receptors on the cell surface of macrophages play an important role in host defence through their ability to bind microbial ligands and induce phagocytosis. concurrently, signal transduction pathways are initiated that aid in defence mechanisms against the invading microbe. here we report on the function of scavenger receptor marco (macrophage receptor with collagenous structure) during infection of zebrafish embryos with mycobacterium marinum, a close relative of m. tuberculosis. morp ...201425086293
correlation of phenotypic profiles using targeted proteomics identifies mycobacterial esx-1 substrates.the esx/wxg-100 (esat-6/wss) exporters are multiprotein complexes that promote protein translocation across the cytoplasmic membrane in a diverse range of pathogenic and nonpathogenic bacterial species. the esx-1 (esat-6 system-1) system mediates virulence factor translocation in mycobacterial pathogens, including the human pathogen mycobacterium tuberculosis. although several genes have been associated with esx-1-mediated transport and virulence, the contribution of individual esx-1 genes to ex ...201425106450
correlative light and electron microscopy imaging of autophagy in a zebrafish infection model.high-resolution imaging of autophagy has been used intensively in cell culture studies, but so far it has been difficult to visualize this process in detail in whole animal models. in this study we present a versatile method for high-resolution imaging of microbial infection in zebrafish larvae by injecting pathogens into the tail fin. this allows visualization of autophagic compartments by light and electron microscopy, which makes it possible to correlate images acquired by the 2 techniques. u ...201425126731
homeostasis of n-α-terminal acetylation of esxa correlates with virulence in mycobacterium marinum.the mycobacterial esx-1 (esat-6 system 1) exporter translocates virulence factors across the cytoplasmic membrane to the cell wall, cell surface, and the bacteriological medium in vitro. the mechanisms underlying substrate targeting to distinct locations are unknown. several esx-1 substrates are n-α-terminally acetylated. the role of this rare modification in bacteria is unclear. we sought to identify genes required for esx-1 substrate modification, transport, and localization. pathogenic mycoba ...201425135684
enhanced recovery, enrichment and detection of mycobacterium marinum with the portable microbe enrichment unit (pmeu).the use of pmeu significantly accelerated the growth of otherwise slowly growing mycobacterium sp. compared to the static reference cultures, m. marinum was detected after 24-48h of cultivation in the pmeu spectrion(®) equipped with infrared (ir) sensors. parallel static cultures did not exhibit or indicate mycobacterial growth within these time limits, and essentially no growth was found in them. the pmeu approach could provide a powerful tool for the rapid diagnosis and determination of enviro ...201425156813
rna sequencing of facs-sorted immune cell populations from zebrafish infection models to identify cell specific responses to intracellular pathogens.the zebrafish (danio rerio) is increasingly used as a model for studying infectious diseases. this nonmammalian vertebrate host, which is transparent at the early life stages, is especially attractive for live imaging of interactions between pathogens and host cells. a number of useful fluorescent reporter lines have recently been developed and significant advances in rna sequencing technology have been made, which now make it possible to apply the zebrafish model for investigating changes in tr ...201425172286
treatment of sporotrichoid fish tank granuloma with pulsed clarithromycin.there is no established therapy of choice for mycobacterium marinum skin infections; clarithromycin monotherapy was used in some anecdotical cases at changeable daily doses and length.201425228273
functional characterization of receptor-interacting serine/threonine kinase 2 (rip2) of the goldfish (carassius auratus l.).we report on the functional characterization of rip2 of the goldfish. quantitative expression analysis of goldfish rip2 revealed the greatest mrna levels in the spleen, monocytes and splenocytes. we generated a recombinant form of the molecule (rgrip2) and determined that anti-human rip2 polyclonal antibody specifically recognized recombinant goldfish rip2 (rgrip2). goldfish rip2 activity was inhibited by the p38 mapk pathway inhibitor sb203580. treatment of goldfish macrophages with lps, pgn, m ...201525242011
macrophage-expressed perforins mpeg1 and mpeg1.2 have an anti-bacterial function in zebrafish.macrophage-expressed gene 1 (mpeg1) encodes an evolutionarily conserved protein with a predicted membrane attack complex/perforin domain associated with host defence against invading pathogens. in vertebrates, mpeg1/perforin-2 is an integral membrane protein of macrophages, suspected to be involved in the killing of intracellular bacteria by pore-forming activity. zebrafish have 3 copies of mpeg1; 2 are expressed in macrophages, whereas the third could be a pseudogene. the mpeg1 and mpeg1.2 gene ...201525247677
a second-order high-resolution finite difference scheme for a size-structured model for the spread of mycobacterium marinum.we present a second-order high-resolution finite difference scheme to approximate the solution of a mathematical model of the transmission dynamics of mycobacterium marinum (mm) in an aquatic environment. this work extends the numerical theory and continues the preliminary studies on the model first developed in ackleh et al. [structured models for the spread of mycobacterium marinum: foundations for a numerical approximation scheme, math. biosci. eng. 11 (2014), pp. 679-721]. numerical simulati ...201525271885
osteomyelitis at two noncontiguous sites caused by mycobacterium marinum in an immunocompetent host: case report and literature review.nontuberculous mycobacteria are rare causes of skin, soft tissue, and musculoskeletal infections. mycobacterium marinum remains one of the most commonly encountered mycobacterial species in humans, causing superficial cutaneous as well as deep infections. we are reporting a case of m. marinum osteomyelitis involving two primary noncontiguous sites in an immunocompetent host, which was successfully treated with surgical drainage and antibiotic therapy.201425306800
molecular and functional characterization of the scavenger receptor cd36 in zebrafish and common carp.cd36 is a scavenger receptor which has been studied closely in mammals where it is expressed by many different cell types and plays a role in highly diverse processes, both homeostatic and pathologic. it is among other things important in the innate immune system, in angiogenesis, and in clearance of apoptotic cells, and it is also involved in lipid metabolism and atherosclerosis. recently, in the cephalochordate amphioxus a primitive cd36 family member was described, which was present before th ...201525306962
exploration of piperidinols as potential antitubercular agents.novel drugs to treat tuberculosis are required and the identification of potential targets is important. piperidinols have been identified as potential antimycobacterial agents (mic < 5 μg/ml), which also inhibit mycobacterial arylamine n-acetyltransferase (nat), an enzyme essential for mycobacterial survival inside macrophages. the nat inhibition involves a prodrug-like mechanism in which activation leads to the formation of bioactive phenyl vinyl ketone (pvk). the pvk fragment selectively form ...201425310152
synthesis and antimycobacterial evaluation of natural oridonin and its enmein-type derivatives.a series of enmein-type derivatives were synthesized and assayed for their antimycobacterial effects. the structures of the synthesized compounds were established by (1)h nmr, (13)c nmr and mass spectral analysis. all the compounds were screened for their antimycobacterial properties against mycobacterium phlei, mycobacterium smegmatis and mycobacterium marinum. compounds 2, 6g and 6i were found to exhibit potent antimycobacterial activity against m. phlei at a concentration of 0.5 μg/ml, which ...201425316557
testing tuberculosis drug efficacy in a zebrafish high-throughput translational medicine screen.the translational value of zebrafish high-throughput screens can be improved when more knowledge is available on uptake characteristics of potential drugs. we investigated reference antibiotics and 15 preclinical compounds in a translational zebrafish-rodent screening system for tuberculosis. as a major advance, we have developed a new tool for testing drug uptake in the zebrafish model. this is important, because despite the many applications of assessing drug efficacy in zebrafish research, th ...201525385118
animal models of tuberculosis: zebrafish.over the past decade the zebrafish (danio rerio) has become an attractive new vertebrate model organism for studying mycobacterial pathogenesis. the combination of medium-throughput screening and real-time in vivo visualization has allowed new ways to dissect host pathogenic interaction in a vertebrate host. furthermore, genetic screens on the host and bacterial sides have elucidated new mechanisms involved in the initiation of granuloma formation and the importance of a balanced immune response ...201425414379
imaging cytosolic translocation of mycobacteria with two-photon fluorescence resonance energy transfer microscopy.transition from latency to active tuberculosis requires mycobacterium tuberculosis (mtb) to penetrate the phagosomal membrane and translocate to the cytosol of the host macrophage. quantitative two-photon fluorescence resonance energy transfer (fret) microscopy is developed to measure cytosolic translocation using mycobacterium marinum (mm) as a model organism for mtb. macrophages were infected with mm or non-pathogenic mycobacterium smegmatis (ms) as a control, then loaded with a fret substrate ...201425426325
infections caused by non-tuberculous mycobacteria in recipients of hematopoietic stem cell transplantation.non-tuberculous mycobacteria (ntm) are acid-fast bacteria that are ubiquitous in the environment and can colonize soil, dust particles, water sources, and food supplies. they are divided into rapidly growing mycobacteria such as mycobacterium fortuitum, mycobacterium chelonae, and mycobacterium abscessus as well as slowly growing species such as mycobacterium avium, mycobacterium kansasii, and mycobacterium marinum. about 160 different species, which can cause community acquired and health care- ...201425426446
interception of host angiogenic signalling limits mycobacterial growth.pathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas that are the hallmark of tuberculosis. here we examine the development and consequences of vascularization of the tuberculous granuloma in the zebrafish-mycobacterium marinum infection model, which is characterized by organized granulomas with necrotic cores that bear striking resemblance to those of human tuberculosis. using intravital microscopy in the transparent larval zebrafish, we show that granul ...201525470057
dram1 promotes the targeting of mycobacteria to selective autophagy.autophagy provides an important defense mechanism against intracellular bacteria, such as mycobacterium tuberculosis (mtb), the causative agent of tuberculosis disease (tb). we recently reported that pathogen recognition and antibacterial autophagy are connected by the induction of the dna damage-regulated autophagy modulator dram1 via the toll-like receptor (tlr)-myd88-nfkb innate immunity signaling pathway. having shown that dram1 colocalizes with mtb in human macrophages, we took advantage of ...201425484076
analysis of rnaseq datasets from a comparative infectious disease zebrafish model using genetiles bioinformatics.we present a rna deep sequencing (rnaseq) analysis of a comparison of the transcriptome responses to infection of zebrafish larvae with staphylococcus epidermidis and mycobacterium marinum bacteria. we show how our developed genetiles software can improve rnaseq analysis approaches by more confidently identifying a large set of markers upon infection with these bacteria. for analysis of rnaseq data currently, software programs such as bowtie2 and samtools are indispensable. however, these progra ...201425503064
necrotizing soft tissue infection occurring after exposure to mycobacterium marinum.cutaneous infections caused by mycobacterium marinum have been attributed to aquarium or fish exposure after a break in the skin barrier. in most instances, the upper limbs and fingers account for a majority of the infection sites. while previous cases of necrotizing soft tissue infections related to m. marinum have been documented, the importance of our presenting case is to illustrate the aggressive nature of m. marinum resulting in a persistent necrotizing soft tissue infection of a finger th ...201425506004
mycobacterium marinum infection initially diagnosed as metastatic crohn's disease. 201625510444
mycobacterium marinum mgtc plays a role in phagocytosis but is dispensable for intracellular multiplication.mgtc is a virulence factor involved in intramacrophage growth that has been reported in several intracellular pathogens, including mycobacterium tuberculosis and salmonella enterica serovar typhimurium. mgtc participates also in adaptation to mg2+ deprivation. herein, we have constructed a mgtc mutant in mycobacterium marinum to further investigate the role of mgtc in mycobacteria. we show that the m. marinum mgtc gene (mma mgtc) is strongly induced upon mg2+ deprivation and is required for opti ...201425545682
biosynthesis of cell envelope-associated phenolic glycolipids in mycobacterium marinum.phenolic glycolipids (pgls) are polyketide synthase-derived glycolipids unique to pathogenic mycobacteria. pgls are found in several clinically relevant species, including various mycobacterium tuberculosis strains, mycobacterium leprae, and several nontuberculous mycobacterial pathogens, such as m. marinum. multiple lines of investigation implicate pgls in virulence, thus underscoring the relevance of a deep understanding of pgl biosynthesis. we report mutational and biochemical studies that in ...201525561717
the cxcr3-cxcl11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection.the recruitment of leukocytes to infectious foci depends strongly on the local release of chemoattractant mediators. the human cxc chemokine receptor 3 (cxcr3) is an important node in the chemokine signaling network and is expressed by multiple leukocyte lineages, including t cells and macrophages. the ligands of this receptor originate from an ancestral cxcl11 gene in early vertebrates. here, we used the optically accessible zebrafish embryo model to explore the function of the cxcr3-cxcl11 axi ...201525573892
non-tuberculous mycobacterial infections of the hand.non-tuberculous mycobacterial infections of the hand are difficult to treat and require a long time before remission. but how long should we wait to see an improvement? to answer this question, the published scientific literature was reviewed in english, french and german. tuberculosis, arthritis and osteomyelitis cases were excluded. a total of 241 non-tuberculous mycobacterial hand infections in 38 scientific publications were retrieved. most were case reports or series. the median age of the ...201525579828
monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of mycobacterium tuberculosis.tuberculosis (tb) is a major public health concern worldwide with over 2 billion people currently infected. the rise of strains of mycobacterium tuberculosis (mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (mdr), extensively drug resistant (xdr) and totally drug resistant (tdr) strains, is of particular concern and new anti-tb drugs are urgently needed. curcumin, a natural product used in traditional medicine in india, exhibits anti-microb ...201525618016
the proprotein convertase subtilisin/kexin furina regulates zebrafish host response against mycobacterium marinum.tuberculosis is a chronic bacterial disease with a complex pathogenesis. an effective immunity against mycobacterium tuberculosis requires both the innate and adaptive immune responses, including proper t helper (th) type 1 cell function. furin is a proprotein convertase subtilisin/kexin (pcsk) enzyme, which is highly expressed in th1 type cells. furin expression in t cells is essential for maintaining peripheral immune tolerance, but its role in the innate immunity and infections has remained e ...201525624351
synthesis of unusual n-acylated aminosugar fragments of mycobacterium marinum lipooligosaccharide iv.a convergent strategy was developed for the stereoselective synthesis of four unusual n-acylated monosaccharides (5-8), which are fragments of lipooligosaccharide iv (los-iv) from mycobacterium marinum. a critical substrate-controlled asymmetric cyclization of an amino acid derived oxazolidine provided a key lactam intermediate 11, which was successfully converted to targets 5-7. the key step in the synthesis of 8 was a one-pot cascade oxidation-cyclization-oxidation reaction of a boc-protected ...201525642627
the autophagic machinery ensures nonlytic transmission of mycobacteria.in contrast to mechanisms mediating uptake of intracellular bacterial pathogens, bacterial egress and cell-to-cell transmission are poorly understood. previously, we showed that the transmission of pathogenic mycobacteria between phagocytic cells also depends on nonlytic ejection through an f-actin based structure, called the ejectosome. how the host cell maintains integrity of its plasma membrane during the ejection process was unknown. here, we reveal an unexpected function for the autophagic ...201525646440
osteomyelitis infection of mycobacterium marinum: a case report and literature review.mycobacterium marinum (m. marinum) is a ubiquitous waterborne organism that grows optimally at temperatures around 30°c. it is a nontuberculous mycobacterium found in nonchlorinated water with worldwide prevalence. it is the most common atypical mycobacterium that causes opportunistic infection in humans. m. marinum can cause superficial infections and localized invasive infections in humans, with the hands being the sites most frequently affected. it can cause skin lesions, which are either sin ...201525664190
insight into cofactor recognition in arylamine n-acetyltransferase enzymes: structure of mesorhizobium loti arylamine n-acetyltransferase in complex with coenzyme a.arylamine n-acetyltransferases (nats) are xenobiotic metabolizing enzymes that catalyze the acetyl-coa-dependent acetylation of arylamines. to better understand the mode of binding of the cofactor by this family of enzymes, the structure of mesorhizobium loti nat1 [(rhilo)nat1] was determined in complex with coa. the f42w mutant of (rhilo)nat1 was used as it is well expressed in escherichia coli and displays enzymatic properties similar to those of the wild type. the apo and holo structures of ( ...201525664736
treatment of mycobacterium marinum with lymecycline: new therapeutic alternative?skin infections by mycobacterium marinum are quite rare in our environment and, therefore, little studied. the majority of the lesions appear three weeks after traumas in aquariums, beaches and fish tanks. lymph node drainage and systematization of the disease are rare and most lesions disappear in about three years. this case aims to show the effectiveness of the treatment used (lymecycline 150 mg/orally/day). this medication may be a new therapeutic option for the treatment of mycobacterium ma ...201525672310
macrophage-microglia networks drive m1 microglia polarization after mycobacterium infection.central nervous system tuberculosis (cns-tb) is caused by infection with mycobacterium tuberculosis (mtb). the inflammatory response following cns-tb involves the activation of resident microglia and the infiltration of macrophages. however, it has not been clarified whether microglia can be polarized into the classically activated proinflammatory m1 phenotype or the alternatively activated anti-inflammatory m2 phenotype after mtb infection. in this study, we found that bv2 treated with conditio ...201525687640
genome-wide transposon mutagenesis indicates that mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts.the interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. to test this hypothesis on a genome-wide level, we determined for the intracellular pathogen mycobacterium marinum whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. using transposon-directed insertion site ...201525690095
skin and subcutaneous infections in south-east asia.we reviewed current literature on four different skin and subcutaneous infections which are often touted as 'emerging diseases' of south-east asia, namely melioidosis, penicilliosis, sporotrichosis and mycobacterium marinum infection. lack of consensus treatment guidelines, high treatment costs and limited investigative capability in certain endemic areas are among the challenges faced by managing physicians. with the increase in borderless travelling, it is hoped that this review will facilitat ...201525706913
lipid droplet dynamics at early stages of mycobacterium marinum infection in dictyostelium.lipid droplets exist in virtually every cell type, ranging not only from mammals to plants, but also to eukaryotic and prokaryotic unicellular organisms such as dictyostelium and bacteria. they serve among other roles as energy reservoir that cells consume in times of starvation. mycobacteria and some other intracellular pathogens hijack these organelles as a nutrient source and to build up their own lipid inclusions. the mechanisms by which host lipid droplets are captured by the pathogenic bac ...201525772333
live imaging of mycobacterium marinum infection in dictyostelium discoideum.the dictyostelium discoideum-mycobacterium marinum host-pathogen system is a recently established and powerful model system for mycobacterial infection. in this chapter, two simple protocols for live imaging of dictyostelium discoideum infection are described. the first method is used to monitor the dynamics of recruitment of gfp-tagged dictyostelium discoideum proteins at single time-points corresponding to the main stages of the infection (1.5-72 h post infection). the second method focuses at ...201525779329
electromechanical cell lysis using a portable audio device: enabling challenging sample preparation at the point-of-care.audio sources are ubiquitously available on portable electronic devices, including cell phones. here we demonstrate lysis of mycobacterium marinum and staphylococcus epidermidis bacteria utilizing a portable audio device coupled with a simple and inexpensive electromagnetic coil. the resulting alternating magnetic field rotates a magnet in a tube with the sample and glass beads, lysing the cells and enabling sample preparation for these bacteria anywhere there is a cell phone, mp3 player, laptop ...201525797443
mycobacterium marinum infection: a case report.the infection by mycobacterium marinum in humans is relatively uncommon. when it occurs, it mainly affects the skin, usually with a chronic, indolent and benign evolution. the diagnosis requires a high index of suspicion, and a significant delay may be observed between the first symptoms to the final diagnosis. this present case reports a m. marinum infection in an immunocompetent patient that had a chronic undiagnosed injury on the dominant hand for at least five years. the patient had several ...201525806076
a mycobacterial phosphoribosyltransferase promotes bacillary survival by inhibiting oxidative stress and autophagy pathways in macrophages and zebrafish.mycobacterium tuberculosis employs various strategies to modulate host immune responses to facilitate its persistence in macrophages. the m. tuberculosis cell wall contains numerous glycoproteins with unknown roles in pathogenesis. here, by using concanavalin a and lc-ms analysis, we identified a novel mannosylated glycoprotein phosphoribosyltransferase, encoded by rv3242c from m. tuberculosis cell walls. homology modeling, bioinformatic analyses, and an assay of phosphoribosyltransferase activi ...201525825498
twenty-eight cases of mycobacterium marinum infection: retrospective case series and literature review.invasive mycobacterium marinum disease (tenosynovitis and osteomyelitis) may be an increasingly common manifestation of m. marinum infection that presents unique diagnostic and therapeutic challenges. we conducted a retrospective case series and literature review of m. marinum infection to better understand the clinical spectrum of invasive versus cutaneous disease.201525869820
coupling capillary zone electrophoresis with electron transfer dissociation and activated ion electron transfer dissociation for top-down proteomics.top-down proteomics offers the potential for full protein characterization, but many challenges remain for this approach, including efficient protein separations and effective fragmentation of intact proteins. capillary zone electrophoresis (cze) has shown great potential for separation of intact proteins, especially for differentially modified proteoforms of the same gene product. to date, however, cze has been used only with collision-based fragmentation methods. here we report the first imple ...201525893372
mkan27435 is required for the biosynthesis of higher subclasses of lipooligosaccharides in mycobacterium kansasii.lipooligosaccharides are glycolipids found in the cell wall of many mycobacterial species including the opportunistic pathogen mycobacterium kansasii. the genome of m. kansasii atcc12478 contains a cluster with genes orthologous to mycobacterium marinum los biosynthesis genes. to initiate a genetic dissection of this cluster and demonstrate its role in los biosynthesis in m. kansasii, we chose mkan27435, a gene encoding a putative glycosyltransferase. using specialized transduction, a phage-base ...201525893968
tropical plant extracts modulating the growth of mycobacterium ulcerans.mycobacterium ulcerans, the etiologic agent of buruli ulcer, has been detected on aquatic plants in endemic tropical regions. here, we tested the effect of several tropical plant extracts on the growth of m. ulcerans and the closely related mycobacterium marinum. m. ulcerans and m. marinum were inoculated on middlebrook 7h11 medium with and without extracts from tropical aquatic plants, including ammannia gracilis, crinum calamistratum, echinodorus africanus, vallisneria nana and vallisneria tor ...201525905816
essential role of the esx-5 secretion system in outer membrane permeability of pathogenic mycobacteria.mycobacteria possess different type vii secretion (t7s) systems to secrete proteins across their unusual cell envelope. one of these systems, esx-5, is only present in slow-growing mycobacteria and responsible for the secretion of multiple substrates. however, the role of esx-5 substrates in growth and/or virulence is largely unknown. in this study, we show that esx-5 is essential for growth of both mycobacterium marinum and mycobacterium bovis. remarkably, this essentiality can be rescued by in ...201525938982
cpsa, a lytr-cpsa-psr family protein in mycobacterium marinum, is required for cell wall integrity and virulence.lytr-cpsa-psr family proteins play an important role in bacterial cell wall integrity. although the pathogenic relevance of lytr-cpsa-psr family proteins has been studied in a few bacterial pathogens, their function in mycobacteria remains uncharacterized. in this work, a transposon insertion mutant (cpsa::tn) of mycobacterium marinum was studied. we found that inactivation of cpsa altered bacterial colony morphology, sliding motility, cell surface hydrophobicity, and cell wall permeability. bes ...201525939506
phylogenetic analysis of vitamin b12-related metabolism in mycobacterium tuberculosis.comparison of genome sequences from clinical isolates of mycobacterium tuberculosis with phylogenetically-related pathogens mycobacterium marinum, mycobacterium kansasii, and mycobacterium leprae reveals diversity amongst genes associated with vitamin b12-related metabolism. diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (snps) with predicted impact on protein function and transcriptional regulation. d ...201525988174
mycobacterial pathogenomics and evolution.most mycobacterial species are harmless saprophytes, often found in aquatic environments. a few species seem to have evolved from this pool of environmental mycobacteria into major human pathogens, such as mycobacterium tuberculosis, the agent of tuberculosis, mycobacterium leprae, the leprosy bacillus, and mycobacterium ulcerans, the agent of buruli ulcer. while the pathogenicity of m. ulcerans relates to the acquisition of a large plasmid encoding a polyketide-derived toxin, the molecular mech ...201426082120
first demonstration of antigen induced cytokine expression by cd4-1+ lymphocytes in a poikilotherm: studies in zebrafish (danio rerio).adaptive immunity in homeotherms depends greatly on cd4+ th cells which release cytokines in response to specific antigen stimulation. whilst bony fish and poikilothermic tetrapods possess cells that express tcr and cd4-related genes (that exist in two forms in teleost fish; termed cd4-1 and cd4-2), to date there is no unequivocal demonstration that cells equivalent to th exist. thus, in this study we determined whether cd4-1+ lymphocytes can express cytokines typical of th cells following antig ...201526083432
genetics of mycobacterial arabinogalactan and lipoarabinomannan assembly.the cell wall of mycobacterium tuberculosis is unique in that it differs significantly from those of both gram-negative and gram-positive bacteria. the thick, carbohydrate- and lipid-rich cell wall with distinct lipoglycans enables mycobacteria to survive under hostile conditions such as shortage of nutrients and antimicrobial exposure. the key features of this highly complex cell wall are the mycolyl-arabinogalactan-peptidoglycan (magp)-based and phosphatidyl-myo-inositol-based macromolecular s ...201426104198
from a fish tank injury to hospital haemodialysis: the serious consequences of drug interactions.we present the case of a 68-year-old man admitted to hospital with severe acute kidney injury secondary to statin-induced rhabdomyolysis. five weeks previously, the patient started a course of clarithromycin for infection of a finger wound with mycobacterium marinum. his current medications included simvastatin, which he continued along with clarithromycin. the severity of the acute kidney injury necessitated initial continuous venovenous haemofiltration followed by 12 haemodialysis sessions bef ...201526106178
a challenging case of multifocal mycobacterium marinum osteoarticular infection in a patient with anorexia nervosa.disseminated infection due to mycobacterium marinum is rare but has been described in immunosuppressed and transplant recipients. we describe a case of multifocal osteoarticular involvement by this pathogen in a patient with anorexia nervosa. serial surgical debridements and a prolonged course of antimicrobial therapy including intravenous amikacin, imipenem, and oral ethambutol and azithromycin were needed to treat the infection. cell mediated immune deficits related to the patient's anorexia n ...201526137337
nontuberculous mycobacteria: skin and soft tissue infections.skin and soft tissue infections caused by nontuberculous mycobacteria are increasing in incidence. the nontuberculous mycobacteria are environmental, acid-fast bacilli that cause cutaneous infections primarily after trauma, surgery and cosmetic procedures. skin findings include abscesses, sporotrichoid nodules or ulcers, but also less distinctive signs. important species include mycobacterium marinum and the rapidly growing mycobacterium: m. fortuitum, m. abscessus and m. chelonae. obtaining tis ...201526143432
phenotypic resistance in mycobacteria: is it because i am old or fat that i resist you?we aimed to explore the phenomenon of phenotypic resistance to antimycobacterial antibiotics and to determine whether this was associated with cell age or the presence of lipid bodies.201526163401
invasive mycobacterium marinum infection. 201526184528
thiopeptide antibiotics exhibit a dual mode of action against intracellular pathogens by affecting both host and microbe.thiostrepton (tsr) is an archetypal thiopeptide antibiotic possessing a quinaldic acid (qa) moiety in the side ring system. according to the mechanism of tsr previously known to target bacterial ribosome, we recently designed and biosynthesized several tsr derivatives that varied in qa substitution. utilizing these thiopeptide antibiotics to treat the intracellular pathogen mycobacterium marinum, we herein report a novel mode of action of tsrs, which induce er stress-mediated autophagy to enhanc ...201526211364
development of an in vitro model system to study the interactions between mycobacterium marinum and teleost neutrophils.the lack of a reliable mammalian neutrophil in vitro culture system has restricted our ability to examine their precise roles in mycobacterial infections. previously, we developed the procedures for the isolation and culture of primary kidney-derived neutrophil-like cells from goldfish that are functionally and morphologically similar to mammalian neutrophils. the cultured primary goldfish neutrophils exhibited prolonged viability and functional effector responses. in this study, we demonstrate ...201526231477
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