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buruli ulcer, a prototype for ecosystem-related infection, caused by mycobacterium ulcerans.buruli ulcer is a noncontagious disabling cutaneous and subcutaneous mycobacteriosis reported by 33 countries in africa, asia, oceania, and south america. the causative agent, mycobacterium ulcerans, derives from mycobacterium marinum by genomic reduction and acquisition of a plasmid-borne, nonribosomal cytotoxin mycolactone, the major virulence factor. m. ulcerans-specific sequences have been readily detected in aquatic environments in food chains involving small mammals. skin contamination com ...201829237707
structural and functional characterisation of the cytochrome p450 enzyme cyp268a2 from mycobacterium marinum.members of the cytochrome p450 monooxygenase family cyp268 are found across a broad range of mycobacterium species including the pathogens mycobacterium avium, m. colombiense,m. kansasii and mmarinum cyp268a2, from m. marinum , which is the first member of this family to be studied, was purified and characterised. cyp268a2 was found to bind a variety of substrates with high affinity, including branched and straight-chain fatty acids (c10-c12), acetate esters, and aromatic compounds. the enzyme w ...201829343612
mycobacterium marinum infection in zebrafish and microglia imitates the early stage of tuberculous meningitis.mycobacterium tuberculosis (m. tuberculosis) invading and activating microglia causes the most serious subtypes of tuberculosis called tubercular meningitis. however, the developmental process of tubercular meningitis, especially the early phase, is poorly understood due to lacking well-established and well-accepted visible models in vitro and in vivo. here, consistent with one recent report, we found mycobacterium marinum (m. marinum) invade the zebrafish brain and subsequently cause granuloma- ...201829352446
using rt qpcr for quantifying mycobacteria marinum from in vitro and in vivo samples.mycobacterium marinum, the causative agent of fish tuberculosis, is rarely a human pathogen causing a chronic skin infection. it is now wildely used as a model system in animal models, especially in zebra fish model, to study the pathology of tuberculosis and as a means of screening new anti-tuberculosis agent. to facilitate such research, quantifying the viable count of m. marinum bacteria is a crucial step. the main approach used currently is still by counting the number of colony forming unit ...201829322466
survey on medicinal plants traditionally used in senegal for the treatment of tuberculosis (tb) and assessment of their antimycobacterial activity.in west africa, populations are used to taking traditional medicine as a first aid against common health problems. in this aspect, many plants are claimed to be effective in the treatment of tuberculosis (tb), which according to the world health organization (who) remains one of the world's deadliest communicable diseases.201729289797
cell envelope stress in mycobacteria is regulated by the novel signal transduction atpase inir in response to trehalose.the cell envelope of mycobacteria is a highly unique and complex structure that is functionally equivalent to that of gram-negative bacteria to protect the bacterial cell. defects in the integrity or assembly of this cell envelope must be sensed to allow the induction of stress response systems. the promoter that is specifically and most strongly induced upon exposure to ethambutol and isoniazid, first line drugs that affect cell envelope biogenesis, is the inibac promoter. in this study, we set ...201729281637
acute infection due to mycobacterium marinum in a patient with ulcerative colitis and metabolic syndrome on infliximab therapy. 201729258704
mycobacterium marinum remains an unrecognized cause of indolent skin infections.we identified 5 patients who had cutaneous lesions with cultures that yielded mycobacterium marinum. it was discovered that all 5 patients had a home aquarium, and infection was preceded by trauma to the hand. however, the association between the development of the infection and exposure of the trauma site to the aquarium was not initially established until repeated questioning was performed. skin biopsies or incision and drainage were performed for all patients, and the diagnosis was establishe ...201729232419
[mycobacterium marinum infection: report of a case]. 201729224287
priming of innate antimycobacterial immunity by heat-killed listeria monocytogenes induces sterilizing response in the adult zebrafish tuberculosis model.mycobacterium tuberculosis remains one of the most problematic infectious agents due to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. host-directed therapies aiming at optimal modulation of immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. in this study, we have established a zebrafish-mycobacterium marinum natural host-pathoge ...201729208761
eczema-like fish tank granuloma: a new clinical presentation of mycobacterium marinum infection. 201729194791
severe inhibition of lipooligosaccharide synthesis induces tlr2-dependent elimination of mycobacterium marinum from thp1-derived macrophages.although mycobacterial glycolipids are among the first-line molecules involved in host-pathogen interactions, their contribution in virulence remains incomplete. mycobacterium marinum is a waterborne pathogen of fish and other ectotherms, closely related to mycobacterium tuberculosis. since it causes tuberculosis-like systemic infection it is widely used as a model organism for studying the pathogenesis of tuberculosis. it is also an occasional opportunistic human pathogen. the m. marinum surfac ...201729183333
whib6 regulation of esx-1 gene expression is controlled by a negative feedback loop in mycobacterium marinum.esx (esat-6 system) export systems play diverse roles across mycobacterial species. interestingly, genetic disruption of esx systems in different species does not result in an accumulation of protein substrates in the mycobacterial cell. however, the mechanisms underlying this observation are elusive. we hypothesized that the levels of esx substrates were regulated by a feedback-control mechanism, linking the levels of substrates to the secretory status of esx systems. to test this hypothesis, w ...201729180415
intra-amoebal killing of mycobacterium ulcerans by acanthamoeba griffini: a co-culture model.mycobacterium ulcerans, a decaying mycobacterium marinum derivative is responsible for buruli ulcer, a notifiable non-contagious disabling infection highly prevalent in some west african countries. aquatic environments are suspected to host m. ulcerans, however, the exact reservoirs remain unknown. while m. marinum was found to resist amoebal microbicidal activities, this remains unknown for m. ulcerans. in this study m. ulcerans was co-cultured with the moderately halophile acanthamoeba griffin ...201729155010
[skin infection due to mycobacterium marinum]. 201729132844
two cases of occupationally acquired mycobacterium marinum infection in chinese restaurant workers in melbourne, australia. 201729076528
local hyperthermia therapy for refractory cutaneous mycobacterium marinum infection. 201729028142
an unusual cutaneous infection caused by mycobacterium marinum.introduction.mycobacterium marinum is a non-tubercular mycobacterium residing in fresh or salt water (in tropical or temperate areas); it is a fish and human pathogen, and in immunocompromised patients can cause severe cutaneous and subcutaneous infections. case presentation. a 46-year-old white man who underwent immunosuppressive therapy was admitted to our department in may 2016 for skin lesions previously diagnosed as 'unusual erysipelas'. we rejected the hypothesis of erysipelas, due to the ...201729026615
partners in crime: phenolic glycolipids and macrophages.two recent articles advance our understanding of mycobacterial pathogenesis, revealing key roles for bacterially derived phenolic glycolipids (pgls). in leprosy, mycobacterium leprae pgl-1 uniquely subverts local macrophages to produce neurotoxic nitric oxide (no), leading to nerve demyelination. in a related model, mycobacterium marinum pgl stimulates the recruitment of growth-conducive monocytes to sites of initial infection as an early immune evasion strategy.201728969977
a fluorescence-based reporter for monitoring expression of mycobacterial cytochrome bd in response to antibacterials and during infection.cytochrome bd is a component of the oxidative phosphorylation pathway in many gram-positive and gram-negative bacteria. next to its role as a terminal oxidase in the respiratory chain this enzyme plays an important role as a survival factor in the bacterial stress response. in mycobacterium tuberculosis and related mycobacterial strains, cytochrome bd is an important component of the defense system against antibacterial drugs. in this report we describe and evaluate an mcherry-based fluorescent ...201728878275
rational design of drug-like compounds targeting mycobacterium marinum melf protein.the mycobacterial mel2 locus (mycobacterial enhanced infection locus, rv1936-1941) is mycobacterium marinum and m. tuberculosis specific, which can withstand reactive oxygen species (ros) and reactive nitrogen species (rns) induced stress. a library of over a million compounds was screened using in silico virtual ligand screening (vls) to identify inhibitors against the modeled structure of melf protein expressed by melf of mel2 locus so that m. marinum's ability to withstand ros/rns stress coul ...201728873466
phenotypic and genomic comparison of mycobacterium aurum and surrogate model species to mycobacterium tuberculosis: implications for drug discovery.tuberculosis (tb) is caused by mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. the considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating m. tuberculosis. these include the use of strains such as mycobacterium smegmatis and mycobacterium ma ...201728705154
detection of mycobacterium marinum, m. peregrinum, m. fortuitum and m. abscessus in aquarium fish. 201728699669
fish pedicure-induced foot mycobacteriosis infection due to mycobacterium marinum: a first case report. 201728677579
a small-molecule allosteric inhibitor of mycobacterium tuberculosis tryptophan synthase.new antibiotics with novel targets are greatly needed. bacteria have numerous essential functions, but only a small fraction of such processes-primarily those involved in macromolecular synthesis-are inhibited by current drugs. targeting metabolic enzymes has been the focus of recent interest, but effective inhibitors have been difficult to identify. we describe a synthetic azetidine derivative, brd4592, that kills mycobacterium tuberculosis (mtb) through allosteric inhibition of tryptophan synt ...201728671682
mycobacterium marinum and carpal tunnel syndrome: three case reports.infection with mycobacterium marinum is often difficult to diagnose. infection with m. marinum in the upper extremity may involve the tendon sheaths, producing clinical manifestations such as tenosynovitis and symptoms of carpal tunnel syndrome. we report 3 cases of m. marinum infection of the hand associated with carpal tunnel syndrome during an outbreak in new york city's chinatown. a combination of carpal tunnel release, flexor tenosynovectomy, and appropriate antibiotics yielded complete res ...201728669531
the brief case: a fishy tale prevents digital doom following polly's peck-the importance of pets in a comprehensive medical history. 201728646087
outbreak of non-tuberculous mycobacteria skin or soft tissue infections associated with handling fish - new york city, 2013-2014.mycobacterium marinum, a bacterium found in freshwater and saltwater, can infect persons with direct exposure to fish or aquariums. during december 2013, the new york city department of health and mental hygiene learned of four suspected or confirmed m. marinum skin or soft tissue infections (sstis) among persons who purchased whole fish from chinese markets. ninety-eight case-patients with non-tuberculous mycobacteria (ntm) sstis were identified with onset june 2013-march 2014. of these, 77 (79 ...201728629484
β-ca-specific inhibitor dithiocarbamate fc14-584b: a novel antimycobacterial agent with potential to treat drug-resistant tuberculosis.inhibition of novel biological pathways in mycobacterium tuberculosis (mtb) creates the potential for alternative approaches for treating drug-resistant tuberculosis. in vitro studies have shown that dithiocarbamate-derived β-carbonic anhydrase (β-ca) inhibitors fc14-594 a and fc14-584b effectively inhibit the activity of mtb β-ca enzymes. we screened the dithiocarbamates for toxicity, and studied the in vivo inhibitory effect of the least toxic inhibitor on m. marinum in a zebrafish model. in o ...201728629306
ohmyungsamycins promote antimicrobial responses through autophagy activation via amp-activated protein kinase pathway.the induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against mycobacterium tuberculosis (mtb), a major pathogenic strain that causes human tuberculosis. in this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (oms) a and b in the antimicrobial responses against mtb infections by activating autophagy in murine bone marrow-derived macrophages (bmdms). oms robustly activated autophagy, which was essentiall ...201728611371
whib4 regulates the pe/ppe gene family and is essential for virulence of mycobacterium marinum.during the course of infection, pathogenic mycobacteria including mycobacterium tuberculosis (m. tb) encounter host environments of variable oxygen tension, ranging from the hypoxic center of granulomas to the most oxygenated region in the lung cavities. mycobacterial responses to changes of oxygen tension are critically related to infection outcomes, such as latency and reactivation. whib4 is an iron-sulfur containing transcription factor that is highly sensitive to oxygen exposure. in this stu ...201728592799
two cases of mycobacterium marinum infection on the upper limbs. 201728556948
characterization of mycobacterium marinum infections in zebrafish wounds and sinus tracts.the impaired healing of mycobacterium tuberculosis-infected wounds is a clinical challenge, and the mechanisms involved are still not clear. the zebrafish model of mycobacterium marinum infection has provided surprising insights into the pathogenesis of tuberculosis in humans. similarly, the major principles and phases of cutaneous wound healing are conserved among adult mammals and adult zebrafish. here, we injected mycobacterium marinum into the dorsal muscles of adult zebrafish and observed t ...201728466489
mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a torc1- and esx-1-dependent manner.autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. however, several bacteria subvert autophagy and benefit from its machinery and functions. monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the esx-1 secretion system of mycobacterium marinum, a close relative to m. tuberculosis, ...201728414774
clinical implications for the timely diagnosis of mycobacterium marinum in the age of biologic therapy: a case report and review of the literature.mycobacterium marinum infections typically present as cutaneous nodular lesions with a sporotrichoid lymphatic spread on extensor surfaces of extremities. the natural history of this infection can be altered if the host is immunosuppressed, leading to disseminated presentations. a detailed exposure history and high degree of suspicion for this indolent pathogen are often required for the correct diagnosis of this disease. we present a case of a 67-year-old male misdiagnosed with seronegative rhe ...201728392952
mycobacterium marinum infection of the hand in an immunocompromised aquarium hobbyist.m. marinum, a nontuberculous mycobacterium, is a rare human pathogen widely distributed in the aquatic environment. in the previous century, epidemics took place due to inadequately chlorinated swimming pool water. nowadays the majority of infections are acquired through contact of previously damaged skin with contaminated fish tank water. we present a case of m. marinum infection of the hand in an aquarium hobbyist which stayed unrecognized for 2 years. after confirming the correct diagnosis, t ...201728511753
cyclophostin and cyclipostins analogs, new promising molecules to treat mycobacterial-related diseases.the progression of mycobacterial diseases requires the development of new therapeutics. here, we evaluated the efficacy and selectivity of a panel of cyclophostin and cyclipostins analogs (cycs) against various bacteria and mycobacteria. the activity of these 26 cycs was first assayed using the agar plate method. compounds exhibiting a 50-100% growth inhibition rate were then selected to determine their mic using the rema assay. the best drug candidate was further tested against mycobacterial cl ...201729241819
a new cinnamic acid derivative from plant-derived endophytic fungus pyronema sp.ten secondary metabolites (1-10) including a new 4-hydroxycinnamic acid derivatives, methyl 2-{(e)-2-[4-(formyloxy)phenyl]ethenyl}-4-methyl-3-oxopentanoate (1), and nine known compounds (2-10) were isolated from an etoac extract derived from a solid rice medium of endophytic fungal strain pyronema sp. (a2-1 & d1-2). their structures were elucidated from nmr and hrms data. all the compounds were tested for antibacterial activity against mycobacterium marinum atccbaa-535. compounds 1, 8 and 9 exhi ...201728391728
inhibitors of mycobacterium marinum virulence identified in a dictyostelium discoideum host model.tuberculosis remains one of the major threats to public health worldwide. given the prevalence of multi drug resistance (mdr) in mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. in this study, we used a dictyostelium discoideum host model to assess virulence ...201728727774
spatio-temporal study of environmental nontuberculous mycobacteria isolated from wardha district in central india.during the last two decades, nontuberculous mycobacteria (ntm) have gained in importance but there is still a paucity of data, particularly for environmental isolates. we studied, over a period of two years, the spatio-temporal features of ntm isolates obtained from different environmental sources in wardha district, india. a total of 1398 samples (699 each of soil and water) were tested and 170 (12.2%) yielded ntm isolates, including 123 from soil and 47 from water samples. out of 170 ntm isola ...201728836034
the impact of genome region of difference 4 (rd4) on mycobacterial virulence and bcg efficacy.comparative genome analyses have revealed a number of regions of difference (rd) among mycobacterial species. the functional consequences of most of these genome variations have not been studied. rd4, which encompasses rv1506c-rv1516c of mycobacterium tuberculosis (m. tb) h37rv, is absent in the closely related mycobacterium bovis and m. bovis bacille calmette-guérin (bcg). on the other hand, we previously found that mycobacterium marinum has an extended rd4 which includes a number of genes invo ...201728642843
efficacy of calcium hypochlorite and ultraviolet irradiation against mycobacterium fortuitum and mycobacterium marinum.nontuberculous mycobacteria (ntm) cause opportunistic infections with increasing frequency in immunocompromised humans. water is one of the natural sources for transmission of ntm and plays a major role in the epidemiology of ntm infections. this study evaluated the efficacy of calcium hypochlorite and ultraviolet irradiation (uv) to eliminate potentially zoonotic ntm species such as m. marinum and m. fortuitum.201728776533
acid-fast bacterium detection and identification from paraffin-embedded tissues using a pcr-pyrosequencing method.acid-fast bacterium (afb) identification from formalin-fixed paraffin-embedded (ffpe) tissues is challenging and may not be readily available to the clinical laboratory. a method to detect and identify afb from ffpe tissues using pcr and pyrosequencing (pcr-seq) was developed and evaluated.201728735303
in silico prediction of antibiotic resistance in mycobacterium ulcerans agy99 through whole genome sequence analysis.buruli ulcer is an emerging infectious disease caused by mycobacterium ulcerans that has been reported from 33 countries. antimicrobial agents either alone or in combination with surgery have been proved to be clinically relevant and therapeutic strategies have been deduced mainly from the empirical experience. the genome sequences of m. ulcerans strain agy99, m. ulcerans ecovar liflandii, and three mycobacterium marinum strains were analyzed to predict resistance in these bacteria. fourteen put ...201728749770
microbial offense vs host defense: who controls the tb granuloma?the granuloma is the hallmark of tuberculosis and simultaneously signifies acquisition of an infection and induction of a host immune response. but who benefits more from the development of the granuloma, the host or the pathogen? is microbe or man dictating disease course and progression? mycobacterial diseases affect humans and animals alike, and the concepts presented in this review reflect host-pathogen interactions that influence not only mycobacterial granulomas in humans and animals but a ...201728749750
active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to mycobacterium marinum.the mechanisms governing neutrophil response to mycobacterium tuberculosis remain poorly understood. in this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to mycobacterium marinum, a close genetic relative of m. tuberculosis used to model tuberculosis. differential expression analysis following nuclear rna-seq of neutrophil active transcriptomes reveals a significan ...201728747644
identification of novel antigen candidates for a tuberculosis vaccine in the adult zebrafish (danio rerio).tuberculosis (tb) remains a major global health challenge and the development of a better vaccine takes center stage in fighting the disease. for this purpose, animal models that are capable of replicating the course of the disease and are suitable for the early-stage screening of vaccine candidates are needed. a mycobacterium marinum infection in adult zebrafish resembles human tb. here, we present a pre-clinical screen for a dna-based tuberculosis vaccine in the adult zebrafish using an m. mar ...201728742838
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
mycobacterium marinum degrades both triacylglycerols and phospholipids from its dictyostelium host to synthesise its own triacylglycerols and generate lipid inclusions.during a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (fas) and sterols are the major energy and carbon source for mycobacterium tuberculosis. mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. lipid droplets (lds) store fas in form of triacylglycerols (tags) and are energy reservoirs of prokaryotes and eukaryotes. using the dictyostelium discoideum/mycobacterium marinum infection m ...201728103313
mycobacterium tuberculosis and mycobacterium marinum non-homologous end-joining proteins can function together to join dna ends in escherichia coli.mycobacterium tuberculosis and mycobacterium smegmatis express a ku protein and a dna ligase d and are able to repair dna double strand breaks (dsbs) by non-homologous end-joining (nhej). this pathway protects against dna damage when bacteria are in stationary phase. mycobacterium marinum is a member of this mycobacterium family and like m. tuberculosis is pathogenic. m. marinum lives in water, forms biofilms and infects fish and frogs. m. marinum is a biosafety level 2 (bsl2) organism as it can ...201727613236
atypical mycobacterial infections of the upper extremity: becoming more atypical?background: atypical mycobacterial infections are uncommon and characterized by a chronic, indolent course before diagnosis. historically, these infections are associated with marine-related injury and/or immune dysfunction. our institution has successfully diagnosed and treated an increasing number of these infections. the objective of this study is to review our experience with these rare infections and verify the developing trends encountered. methods: a retrospective review was performed for ...201728344532
recombinant bcg expressing esx-1 of mycobacterium marinum combines low virulence with cytosolic immune signaling and improved tb protection.recent insights into the mechanisms by which mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. the only licensed anti-tuberculosis vaccine, mycobacterium bovis bcg, provides limited protection. a feature of bcg is the partial deletion of the esx-1 type vii secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked t ...201728297677
mycobacterium marinum.mycobacterium marinum is a well-known pathogenic mycobacterium for skin and soft tissue infections and is associated with fishes and water. among nontuberculous mycobacteria (ntm), it is the leading cause of extrarespiratory human infections worldwide. in addition, there is a specific scientific interest in m. marinum because of its genetic relatedness to mycobacterium tuberculosis and because experimental infection of m. marinum in fishes mimics tuberculosis pathogenesis. microbiological charac ...201728387180
chronic cutaneous mycobacterial ulcers due to mycobacterium ulcerans (buruli ulcer): the first indigenous case report from jordan and a literature review.buruli ulcer is the third most common mycobacterial infection worldwide. it is endemic in tropical, subtropical, and temperate climates. it causes devastating disease with morbidity and mortality. the treatment duration is long and the regimens considered are limited. chronic cutaneous ulcers of mycobacterial etiology have been reported previously in amman, but these were not associated with mycobacterium ulcerans infection.201728344056
the chemokine receptor cxcr4 promotes granuloma formation by sustaining a mycobacteria-induced angiogenesis programme.cxc chemokine receptor 4 plays a critical role in chemotaxis and leukocyte differentiation. furthermore, there is increasing evidence that links this receptor to angiogenesis. using the well-established zebrafish-mycobacterium marinum model for tuberculosis, angiogenesis was recently found to be important for the development of cellular aggregates called granulomas that contain the mycobacteria and are the hallmark of tuberculosis disease. here, we found that initiation of the granuloma-associat ...201728332618
[nontuberculous mycobacteria].dermatologically relevant nontuberculous mycobacteria (ntm) include mycobacterium marinum and mycobacterium ulcerans and different rapidly growing mycobacteria (rgm). rgm are widely present in the environment and are facultative pathogenic. diagnostic detection of nontuberculous mycobacteria is frequently challenging. immune-competent individuals mostly develop localized infections. immune-suppressed patients may present with severe and disseminated disease. in these cases, rapid initiation of m ...201728331949
mycolactone-producing mycobacterium marinum infection in captive hong kong warty newts and pathological evidence of impaired host immune function.a mass mortality event of captive hong kong warty newts paramesotriton hongkongensis with non-granulomatous necrotic lesions occurred in taipei zoo, taiwan, in 2014. clinically, the sick newts were lethargic and often covered with water mold saprolegnia sp. on the skin of the body trunk or extremities. predominant pathological findings were multifocal non-granulomatous necrotic lesions in the liver, spleen, and kidneys and severe skin infection with saprolegnia sp., with deep invasion and involv ...201728322210
dynamic regulation of fatty acid pools for improved production of fatty alcohols in saccharomyces cerevisiae.in vivo production of fatty acid-derived chemicals in saccharomyces cerevisiae requires strategies to increase the intracellular supply of either acyl-coa or free fatty acids (ffas), since their cytosolic concentrations are quite low in a natural state for this organism. deletion of the fatty acyl-coa synthetase genes faa1 and faa4 is an effective and straightforward way to disable re-activation of fatty acids and drastically increase ffa levels. however, this strategy causes ffa over-accumulati ...201728298234
regulation of phagocyte triglyceride by a stat-atg2 pathway controls mycobacterial infection.mycobacterium tuberculosis remains a global threat to human health, yet the molecular mechanisms regulating immunity remain poorly understood. cytokines can promote or inhibit mycobacterial survival inside macrophages and the underlying mechanisms represent potential targets for host-directed therapies. here we show that cytokine-stat signalling promotes mycobacterial survival within macrophages by deregulating lipid droplets via atg2 repression. in drosophila infected with mycobacterium marinum ...201728262681
functional characterisation of the drosophila cg6568 gene in host defence against mycobacterium marinum.mycobacterium marinum is a pathogenic mycobacterial species closely related to mycobacterium tuberculosis. in this study, we established a mycobacterial infection model of drosophila melanogaster to characterize the role played by cg6568, a homolog of the human cathelicidin gene, in the innate defense against infection. drosophila cg6568 was expressed at various levels during all developmental stages, and the expression levels were modulated by m. marinum in a time-dependent manner. 20-hydroxyec ...201728245983
effectiveness of purified methylene blue in an experimental model of mycobacterium ulcerans infection.mycobacterium ulcerans is responsible for buruli ulcer, characterised by extensive, disabling ulcers. standard treatment combining rifampicin and streptomycin exposes patients to toxicity and daily painful injections. in this study, the in vitro susceptibilities of 3 m. ulcerans strains, 1 mycobacterium marinum strain and 18 strains representative of eleven other mycobacterium species and subspecies to methylene blue were determined. whilst growth of m. ulcerans was inhibited by 0.0125 g/l methy ...201728131607
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
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
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
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
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
[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
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 infection initially diagnosed as metastatic crohn's disease. 201625510444
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
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
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
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