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mycobacterial esx-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions.mycobacterium tuberculosis and mycobacterium marinum are thought to exert virulence, in part, through their ability to lyse host cell membranes. the type vii secretion system esx-1 [6-kda early secretory antigenic target (esat-6) secretion system 1] is required for both virulence and host cell membrane lysis. both activities are attributed to the pore-forming activity of the esx-1-secreted substrate esat-6 because multiple studies have reported that recombinant esat-6 lyses eukaryotic membranes. ...201728119503
high-throughput carbon substrate profiling of mycobacterium ulcerans suggests potential environmental reservoirs.mycobacterium ulcerans is a close derivative of mycobacterium marinum and the agent of buruli ulcer in some tropical countries. epidemiological and environmental studies pointed towards stagnant water ecosystems as potential sources of m. ulcerans, yet the ultimate reservoirs remain elusive. we hypothesized that carbon substrate determination may help elucidating the spectrum of potential reservoirs.201728095422
structural basis for the strict substrate selectivity of the mycobacterial hydrolase lipw.the complex life cycle of mycobacterium tuberculosis requires diverse energy mobilization and utilization strategies facilitated by a battery of lipid metabolism enzymes. among lipid metabolism enzymes, the lip family of mycobacterial serine hydrolases is essential to lipid scavenging, metabolic cycles, and reactivation from dormancy. on the basis of the homologous rescue strategy for mycobacterial drug targets, we have characterized the three-dimensional structure of full length lipw from mycob ...201627936614
murine mycobacterium marinum infection as a model for tuberculosis.mycobacteria are a major human health problem globally. regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (manjelievskaia j et al, trans r soc trop med hyg 110: 110, 2016; pereira et al., lancet infect dis 12:300-306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-prevention and available treatments. thus, increased basic understanding of mycobacterial-and particularly ...201727914088
mycobacterium marinum hand infection. 201627910278
[mycobacterium marinum-infektion]. 201627908321
pulmonary mycobacterium marinum infection: 'fish tank granuloma' of the lung.a 65-year-old man presented with a six-month history of lethargy, weight loss and dry cough. he had a background of mild chronic obstructive pulmonary disease. chest radiograph showed new right upper lobe cavitary opacification. sputum cultures were acid-fast bacilli smear positive and yielded mycobacterium marinum - a non-tuberculous mycobacterium (ntm) often found in aquatic environments and rarely associated with respiratory disease. the suspected source was silent aspiration of contaminated ...201627872397
septic arthritis caused by mycobacterium marinum infection. 201627862193
the inflammatory chemokine cxcl18b exerts neutrophil-specific chemotaxis via the promiscuous chemokine receptor cxcr2 in zebrafish.cxcl18b is a chemokine found in zebrafish and in other piscine and amphibian species. cxcl18b is a reliable inflammatory marker; however, its function is yet to be elucidated. here, we found that cxcl18b is chemotactic towards neutrophils, similarly to cxcl8a/interleukin-8, the best characterised neutrophil chemoattractant in humans and teleosts. like cxcl8a, cxcl18b-dependent recruitment required the chemokine receptor cxcr2, while it was unaffected by depletion of the other two neutrophil rece ...201727815178
screening of anti-mycobacterial compounds in a naturally infected zebrafish larvae model.mycobacterium tuberculosis is a deadly human pathogen that causes the lung disease tb. m. tuberculosis latently infects a third of the world's population, resulting in ∼1.5 million deaths per year. due to the difficulties and expense of carrying out animal drug trials using m. tuberculosis and rodents, infections of the zebrafish danio rerio with mycobacterium marinum have become a useful surrogate. however, the infection methods described to date require specialized equipment and a high level o ...201727798206
a nonsense mutation in mycobacterium marinum that is suppressible by a novel mechanism.mycobacterial pathogens use the esat-6 system 1 (esx-1) exporter to promote virulence. previously, we used gene disruption and complementation to conclude that the mmar_0039 gene in mycobacterium marinum is required to promote esx-1 export. here we applied molecular genetics, proteomics, and whole-genome sequencing to demonstrate that the mmar_0039 gene is not required for esx-1 secretion or virulence. these findings suggest that we initially observed an indirect mechanism of genetic complementa ...201727789543
a unique pe_pgrs protein inhibiting host cell cytosolic defenses and sustaining full virulence of mycobacterium marinum in multiple hosts.despite intense research, pe_pgrs proteins still represent an intriguing aspect of mycobacterial pathogenesis. these cell surface proteins influence virulence in several pathogenic species, but their diverse and exact functions remain unclear. herein, we focussed on a pe_pgrs member from mycobacterium marinum, mmar_0242, characterized by an extended and unique c-terminal domain. we demonstrate that an m. marinum mutant carrying a transposon insertion in mmar_0242 is highly impaired in its abilit ...201627120981
macrophage epithelial reprogramming underlies mycobacterial granuloma formation and promotes infection.mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. here, using the zebrafish-mycobacterium marinum model, we found that mycobacter ...201627760340
macrophages' choice: take it in or keep it out.in tuberculosis, some macrophages in granulomas assume an epitheloid appearance. using the mycobacterium marinum-zebrafish model, cronan et al. (2016) now show that granuloma macrophages undergo reprograming events involving e-cadherin-dependent formation of epithelial-like cell-cell junctions. interference with the function of e-cadherin in macrophages disorganized the granulomas and protected the fish, introducing new ideas and questions about macrophage function and granulomatous diseases.201627760333
[skin infection by mycobacterium marinum]. 201627686936
synthesis and antimicrobial evaluation of 1-[(2-substituted phenyl)carbamoyl]naphthalen-2-yl carbamates.series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. primary in vitro screening of the synthesized compounds was performed against staphylococcus aureus, two methicillin-resistant s. aureus strains, mycobacterium marinum, and m. kansasii. 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate and 1-[(2-nitrophenyl)carbamoyl]naphtha ...201627617988
esxa membrane-permeabilizing activity plays a key role in mycobacterial cytosolic translocation and virulence: effects of single-residue mutations at glutamine 5.esxa is required for virulence of mycobacterium tuberculosis (mtb) and plays an essential role in phagosome rupture and translocation to the cytosol of macrophages. recent biochemical studies have demonstrated that esxa is a membrane-permeabilizing protein. however, evidence that link esxa membrane-permeabilizing activity to mtb cytosolic translocation and virulence is lacking. here we found that mutations at glutamine 5 (q5) could up or down regulate esxa membrane-permeabilizing activity. the m ...201627600772
mycobacterium marinum skin infection in a sushi cook. 201627595206
mycobacterium marinum infection with sporotrichoid spread from fish tank exposure. 201627551035
mycobacterial whib6 differentially regulates esx-1 and the dos regulon to modulate granuloma formation and virulence in zebrafish.during the course of infection, mycobacterium tuberculosis (mtb) is exposed to diverse redox stresses that trigger metabolic and physiological changes. how these stressors are sensed and relayed to the mtb transcriptional apparatus remains unclear. here, we provide evidence that whib6 differentially regulates the esx-1 and dosr regulons through its fe-s cluster. when challenged with no, whib6 continually activates expression of the dosr regulons but regulates esx-1 expression through initial act ...201627545883
structural basis for cytokinin production by log from corynebacterium glutamicum."lonely guy" (log) has been identified as a cytokinin-producing enzyme in plants and plant-interacting fungi. the gene product of cg2612 from the soil-dwelling bacterium corynebacterium glutamicum was annotated as an ldc. however, the facts that c. glutamicum lacks an ldc and cg2612 has high amino acid similarity with log proteins suggest that cg2612 is possibly an log protein. to investigate the function of cg2612, we determined its crystal structure at a resolution of 2.3 å. cg2612 functions a ...201627507425
transcriptomic approaches in the zebrafish model for tuberculosis-insights into host- and pathogen-specific determinants of the innate immune response.mycobacterium marinum infection in zebrafish has become a well-established model of tuberculosis. both embryonic and adult zebrafish infection studies have contributed to our knowledge of the development and function of tuberculous granulomas, which are typical of mycobacterial pathogenesis. in this review we discuss how transcriptome profiling studies have helped to characterize this infection process. we illustrate this using new rna sequencing (rna-seq) data that reveals three main phases in ...201627503359
efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis.macrophages and neutrophils are the first responders to invading pathogens and contribute strongly to the host defense against intracellular pathogens. the collective interplay and dynamic interactions between these leukocytes are to a large extent not understood. in the present study, we have investigated their role using a combination of confocal laser-scanning and electron microscopy in a zebrafish model for tuberculosis, a local mycobacterium marinum infection in the tissue of the larval tai ...201627469488
live imaging of host-pathogen interactions in zebrafish larvae.zebrafish larvae are a powerful platform for studying the innate immune response to infection. the small size and optical transparency of larval zebrafish allow for multiple subject, multidimensional, and longitudinal imaging experiments. this chapter describes protocols for infecting zebrafish larvae with their natural pathogen mycobacterium marinum, rapid short-term imaging, long-term extended imaging, and drug treatment assays. these protocols can be easily adapted to image and manipulate hos ...201627464810
mycobacteriosis caused by mycobacterium marinum in reared mullets: first evidence from sardinia (italy).mycobacterium marinum is a slow-growing non-tuberculous mycobacterium, and it is considered the most common aetiologic agent of mycobacteriosis in wild and cultured fish. the diagnosis is principally made by histology when positive ziehl-neelsen stain granulomas are detected. the aim of this study was to investigate the occurrence of mycobacteriosis in extensively cultured mugilidae of two lagoons (cabras and san teodoro) from sardinia by the use of histology, microbiology, pcr and dna sequencin ...201727368155
strategies to mitigate a mycobacterium marinum outbreak in a zebrafish research facility.in 2011, the zebrafish research facility at the university of oregon experienced an outbreak of mycobacterium marinum that affected both research fish and facility staff. a thorough review of risks to personnel, the zebrafish veterinary care program, and zebrafish husbandry procedures at the research facility followed. in the years since 2011, changes have been implemented throughout the research facility to protect the personnel, the fish colony, and ultimately the continued success of the zebr ...201627351618
translocation of nanoparticles and mycobacterium marinum across the intestinal epithelium in zebrafish and the role of the mucosal immune system.nano- and microparticles are promising carrier systems for oral delivery of drugs or vaccines, particularly in fish aquaculture. however, the mechanisms of uptake, trans-epithelial transport and immune response to nano/micrometer sized particles, or microorganisms such as bacteria are poorly understood in fish. here, adult zebrafish were used to study the uptake of different nano- and microparticles and the pathogenic bacteria mycobacterium marinum in the intestine, and their interactions with e ...201727343826
the esx-5 system of pathogenic mycobacteria is involved in capsule integrity and virulence through its substrate ppe10.mycobacteria produce a capsule layer, which consists of glycan-like polysaccharides and a number of specific proteins. in this study, we show that, in slow-growing mycobacteria, the type vii secretion system esx-5 plays a major role in the integrity and stability of the capsule. we have identified ppe10 as the esx-5 substrate responsible for this effect. mutants in esx-5 and ppe10 both have impaired capsule integrity as well as reduced surface hydrophobicity. electron microscopy, immunoblot and ...201627280885
the zebrafish breathes new life into the study of tuberculosis.tuberculosis (tb) is a global health emergency. up to one-third of the world's population is infected with mycobacterium tuberculosis, and the pathogen continues to kill 1.5 million people annually. currently, the means for preventing, diagnosing, and treating tb are unsatisfactory. one of the main reasons for the poor progress in tb research has been a lack of good animal models to study the latency, dormancy, and reactivation of the disease. although sophisticated in vitro and in silico method ...201627242801
the fbpase encoding gene glpx is required for gluconeogenesis, bacterial proliferation and division in vivo of mycobacterium marinum.lipids have been identified as important carbon sources for mycobacterium tuberculosis (mtb) to utilize in vivo. thus gluconeogenesis bears a key role for mtb to survive and replicate in host. a rate-limiting enzyme of gluconeogenesis, fructose 1, 6-bisphosphatase (fbpase) is encoded by the gene glpx. the functions of glpx were studied in m. marinum, a closely related species to mtb. the glpx deletion strain (δglpx) displayed altered gluconeogenesis, attenuated virulence, and altered bacterial p ...201627233038
pyogenic flexor tenosynovitis caused by shewanella algae.pyogenic flexor tenosynovitis is an orthopedic emergency most commonly caused by staphylococcus aureus and streptococci and occasionally, when associated with water exposure, mycobacterium marinum. shewanella algae, a gram-negative bacillus found in warm saltwater environments, has infrequently been reported to cause serious soft tissue infections and necrosis. in this case, s. algae caused complicated flexor tenosynovitis requiring open surgical irrigation and debridement. flexor tenosynovitis ...201627206398
evaluation of the slomyco sensititre(®) panel for testing the antimicrobial susceptibility of mycobacterium marinum isolates.the agar dilution method is currently considered as the reference method for mycobacterium marinum drug susceptibility testing (dst). as it is time-consuming, alternative methods, such as the e-test, were evaluated for m. marinum dst, but without success. the slomyco sensititre(®) panel, recently commercialized by trek diagnostic systems (cleveland, oh), can be used for dst in slow-growing mycobacteria and for antimicrobial agents recommended by the clinical and laboratory standards institute (c ...201627150659
adding insult to injury: exacerbating tb risk with smoking.inhaled environmental pollutants, most prominently from cigarettes, confer an increased risk of tuberculosis. a recent study published in cell by berg et al., (2016) using the zebrafish model of mycobacterium marinum infection provides new insights into the role of macrophage lysosomal engorgement in compromising host defense against mycobacteria.201627078065
esx-1 exploits type i ifn-signalling to promote a regulatory macrophage phenotype refractory to ifnγ-mediated autophagy and growth restriction of intracellular mycobacteria.the ability of macrophages to eradicate intracellular pathogens is normally greatly enhanced by ifnγ, a cytokine produced mainly after onset of adaptive immunity. however, adaptive immunity is unable to provide sterilizing immunity against mycobacteria, suggesting that mycobacteria have evolved virulence strategies to inhibit the bactericidal effect of ifnγ-signalling in macrophages. still, the host-pathogen interactions and cellular mechanisms responsible for this feature have remained elusive. ...201627062290
inorganic phosphate limitation modulates capsular polysaccharide composition in mycobacteria.mycobacterium tuberculosis is protected by an unusual and highly impermeable cell envelope that is critically important for the successful colonization of the host. the outermost surface of this cell envelope is formed by capsular polysaccharides that play an important role in modulating the initial interactions once the bacillus enters the body. although the bioenzymatic steps involved in the production of the capsular polysaccharides are emerging, information regarding the ability of the bacte ...201627044743
lysosomal disorders drive susceptibility to tuberculosis by compromising macrophage migration.a zebrafish genetic screen for determinants of susceptibility to mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. this causes a buildup of unengulfed cell debris. during mycobacterial infect ...201627015311
identification of a novel inhibitor of isocitrate lyase as a potent antitubercular agent against both active and non-replicating mycobacterium tuberculosis.screen and identify novel inhibitors of isocitrate lyase (icl) as potent antitubercular agents against mycobacterium tuberculosis and determine their inhibitory characteristics, antitubercular activities and mechanisms of action.201626980494
design, synthesis and biological evaluation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives as mycobacterium tuberculosis pantothenate synthetase inhibitors.in the present study, we have designed imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives from earlier reported imidazo[1,2-a]pyridine based mycobacterium tuberculosis (mtb) pantothenate synthetase (ps) inhibitors. we synthesized thirty compounds and they were evaluated for mtb ps inhibition study, in vitro anti-tb activities against replicative and non-replicative mtb, in vivo activity using mycobacterium marinum infected zebra fish and cytotoxicity against raw 264.7 cell lin ...201626867485
role of eosinophils and apoptosis in pdims/pgls deficient mycobacterium elimination in adult zebrafish.the cell wall lipids phthiocerol dimycocerosates (pdims) and its structurally-related compound, phenolic glycolipids (pgls) are major virulence factors of mycobacterium, as shown by the reduced growth of pdims/pgls deficient mutants in various animal models. pdims/pgls play active roles in modulating host immune responses. however, the cellular and molecular mechanisms of how pdims/pgls deficient mutant was eliminated in vivo are still elusive. our aim was to investigate what host immune respons ...201626855012
mycobacterium marinum infection after exposure to coal mine water.mycobacterium marinum infection has been historically associated with exposure to aquariums, swimming pools, fish, or other marine fauna. we present a case of m marinum left wrist tenosynovitis and elbow bursitis associated with a puncture injury and exposure to coal mine water in illinois.201626835478
pleiotropic consequences of gene knockouts in the phthiocerol dimycocerosate and phenolic glycolipid biosynthetic gene cluster of the opportunistic human pathogen mycobacterium marinum.phthiocerol dimycocerosates (pdims) and phenolic glycolipids (pgls) contribute to the pathogenicity of several mycobacteria. biosynthesis of these virulence factors requires polyketide synthases and other enzymes that represent potential targets for the development of adjuvant antivirulence drugs. we used six isogenic mycobacterium marinum mutants, each with a different gene knockout in the pdim/pgl biosynthetic pathway, to probe the pleiotropy of mutations leading to pdim(-) pgl(-), pdim(+) pgl ...201626818253
optimization and validation of mycobacterium marinum-induced adult zebrafish model for evaluation of oral anti-tuberculosis drugs.mycobacterium marinum has emerged as a suitable species for induction of tuberculosis-like disease in zebrafish, and various zebrafish models (larval and adult) for drug screening have been proposed in the literature. it is believed that an adult zebrafish model is more useful in drug screening because, apart from assessment of efficacy, one can obtain data on dosage, pharmacokinetics and overall health improvement. this study suggests a simple, cost-effective and resource-efficient protocol for ...201426786625
under the sea: superficial skin infection with an atypical cause.traumatic abrasions on human extremities as a result of direct contact with sea, lake, river, or aquarium animals or from traumatic injuries sustained in seawater may develop into solitary or linear granulomatous lesions. one of the more common microbial etiologies for such infections is mycobacterium marinum. an astute pediatrician, family physician, or nurse practitioner should have a high index of suspicion and obtain specific cultures to support the growth of mycobacterium species. mycobacte ...201626785094
mycobacterium marinum mmar_2318 and mmar_2319 are responsible for lipooligosaccharide biosynthesis and virulence toward dictyostelium.resistance to phagocyte killing is an important virulence factor in mycobacteria. dictyostelium has been used to study the interaction between phagocytes and bacteria, given its similarity to the mammalian macrophage. here, we investigated the genes responsible for virulence to dictyostelium by screening 1728 transposon mutants of the mycobacterium marinum ntuh-m6094 strain. a total of 30 mutants that permissive for dictyostelium growth were identified. these mutants revealed interruptions in 20 ...201526779131
the use of trimethoprim and sulfamethoxazole (tmp-smx) in dermatology.we analyzed publications and articles in the pubmed database about the use of trimethoprim and sulfamethoxazole (tmp-smx) in dermatology. literature published in the english language, at least in the past two decades, was reviewed. specific dermatologic indications for tmp-smx are few but it is often used as the second- or third- line agent. tmp-smx is used to treat cutaneous nocardiosis and aeromonas infections. tmp-smx is a treatment option for cat - scratch disease, granuloma inguinale, melio ...201526774630
[osteo-cutaneous mycobacterium marinum infection of the elbow and reconstruction with radial collateral artery perforator-based propeller flap].mycobacterium marinum is an atypical and non-tuberculosis mycobacterium that mainly leads to cutaneous infections. infections occur through inoculation of the organism through injury to the skin in the presence of contaminated water or fish. the patient often presents with unspecific symptoms and the evolution, in the absence of adequate treatment, is characterized by an expansion of the cutaneous lesion and a spread to deep structures. infections of tendon sheaths and joints are described, rare ...201626748858
clinical and pathological evaluation of mycobacterium marinum group skin infections associated with fish markets in new york city.from december 2013 through may 2014, physicians, dermatopathologists, and public health authorities collaborated to characterize an outbreak of mycobacterium marinum and other nontuberculous mycobacterial skin and soft tissue infections (sstis) associated with handling fish in new york city's chinatown. clinicopathologic and laboratory investigations were performed on a series of patients.201626673347
explosive generalization of nodular vasculitis - mycobacterium marinum challenges the paradigm. 201626551244
biochemical studies of mycobacterial fatty acid methyltransferase: a catalyst for the enzymatic production of biodiesel.transesterification of fatty acids yields the essential component of biodiesel, but current processes are cost-prohibitive and generate waste. recent efforts make use of biocatalysts that are effective in diverting products from primary metabolism to yield fatty acid methyl esters in bacteria. these biotransformations require the fatty acid o-methyltransferase (famt) from mycobacterium marinum (mmfamt). although this activity was first reported in the literature in 1970, the famts have yet to be ...201526526103
mycobacterium marinum infection on the face diagnosed by polymerase chain reaction amplification and direct sequencing. 201526512191
septic arthritis caused by mycobacterium marinum.the incidence of infection by mycobacterium marinum is rising, mainly due to the increasing popularity of home aquariums. the infection typically manifests as skin lesions, with septic arthritis being a rare presentation form. the disease is difficult to diagnose even when there is a high clinical suspicion, as culture in specific media may not yield positive findings. thus, establishment of appropriate treatment is often delayed. synovectomy, capsular thinning, and joint drainage together with ...201626511731
dna vaccination boosts bacillus calmette-guérin protection against mycobacterial infection in zebrafish.despite the widespread use of the current bacillus calmette-guérin (bcg) vaccine, tuberculosis is still a major cause of morbidity and mortality worldwide. vaccination with bcg does not prevent a mycobacterium tuberculosis infection, nor does it inhibit the reactivation of latent tuberculosis. here, we show that adult zebrafish are modestly and variably protected from a mycobacterial infection by bcg vaccination. an intraperitoneal (i.p.) bcg vaccination was associated with enhanced survival upo ...201626363085
protection and pathology in tb: learning from the zebrafish model.zebrafish has earned its place among animal models of tuberculosis. its natural pathogen, mycobacterium marinum, shares major virulence factors with the human pathogen mycobacterium tuberculosis. in adult zebrafish, which possess recombination-activated adaptive immunity, it can cause acute infection or a chronic progressive disease with containment of mycobacteria in well-structured, caseating granulomas. in addition, a low-dose model that closely mimics human latent infection has recently been ...201626324465
discovery of novel lysine ɛ-aminotransferase inhibitors: an intriguing potential target for latent tuberculosis.mycobacterium tuberculosis (mtb) has remarkable ability to persist in the human host and causes latent infection in one third of the world population. currently available tuberculosis (tb) drugs while effective in killing actively growing mtb, is largely ineffective in killing persistent or latent mtb. lysine-ɛ aminotransferase (lat) enzyme is reported to be highly up-regulated (41.86 times) in in vitro models of tb designed to mimic the latent stage. hence inhibition of this mtb lat seems attra ...201526299907
sporotrichoid mycobacterium marinum infection in an elderly woman.we describe the case of an elderly woman who acquired a mycobacterium marinum infection following skin exposure to the bacteria through a small wound on her right ring finger, obtained while preparing fish. the resultant sporotrichoid nodules of the right hand and the distal forearm, refractory to the initial therapy with doxycycline and rifampicin, were successfully treated with oral regimen of clarithromycin.201526295859
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
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
invasive mycobacterium marinum infection. 201526184528
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
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
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
mycobacterium marinum infection initially diagnosed as metastatic crohn's disease. 201625510444
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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