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zebrafish: an animal model for research in veterinary medicine.the zebrafish (danio rerio) has become known as an excellent model organism for studies of vertebrate biology, vertebrate genetics, embryonal development, diseases and drug screening. nevertheless, there is still lack of detailed reports about usage of the zebrafish as a model in veterinary medicine. comparing to other vertebrates, they can lay hundreds of eggs at weekly intervals, externally fertilized zebrafish embryos are accessible to observation and manipulation at all stages of their devel ...201526618602
insight into cofactor recognition in arylamine n-acetyltransferase enzymes: structure of mesorhizobium loti arylamine n-acetyltransferase in complex with coenzyme a.arylamine n-acetyltransferases (nats) are xenobiotic metabolizing enzymes that catalyze the acetyl-coa-dependent acetylation of arylamines. to better understand the mode of binding of the cofactor by this family of enzymes, the structure of mesorhizobium loti nat1 [(rhilo)nat1] was determined in complex with coa. the f42w mutant of (rhilo)nat1 was used as it is well expressed in escherichia coli and displays enzymatic properties similar to those of the wild type. the apo and holo structures of ( ...201525664736
live imaging of mycobacterium marinum infection in dictyostelium discoideum.the dictyostelium discoideum-mycobacterium marinum host-pathogen system is a recently established and powerful model system for mycobacterial infection. in this chapter, two simple protocols for live imaging of dictyostelium discoideum infection are described. the first method is used to monitor the dynamics of recruitment of gfp-tagged dictyostelium discoideum proteins at single time-points corresponding to the main stages of the infection (1.5-72 h post infection). the second method focuses at ...201525779329
lipid droplet dynamics at early stages of mycobacterium marinum infection in dictyostelium.lipid droplets exist in virtually every cell type, ranging not only from mammals to plants, but also to eukaryotic and prokaryotic unicellular organisms such as dictyostelium and bacteria. they serve among other roles as energy reservoir that cells consume in times of starvation. mycobacteria and some other intracellular pathogens hijack these organelles as a nutrient source and to build up their own lipid inclusions. the mechanisms by which host lipid droplets are captured by the pathogenic bac ...201525772333
the autophagic machinery ensures nonlytic transmission of mycobacteria.in contrast to mechanisms mediating uptake of intracellular bacterial pathogens, bacterial egress and cell-to-cell transmission are poorly understood. previously, we showed that the transmission of pathogenic mycobacteria between phagocytic cells also depends on nonlytic ejection through an f-actin based structure, called the ejectosome. how the host cell maintains integrity of its plasma membrane during the ejection process was unknown. here, we reveal an unexpected function for the autophagic ...201525646440
[sporadic cutaneous infections due to nontuberculous mycobacteria: a retrospective study of 37 cases].to study the clinical and pathological characteristics of sporadic cutaneous infections due to nontuberculous mycobacteria (ntm), and investigate the diagnostic criteria and therapeutic principal.201526679654
nontuberculous mycobacteria: skin and soft tissue infections.skin and soft tissue infections caused by nontuberculous mycobacteria are increasing in incidence. the nontuberculous mycobacteria are environmental, acid-fast bacilli that cause cutaneous infections primarily after trauma, surgery and cosmetic procedures. skin findings include abscesses, sporotrichoid nodules or ulcers, but also less distinctive signs. important species include mycobacterium marinum and the rapidly growing mycobacterium: m. fortuitum, m. abscessus and m. chelonae. obtaining tis ...201526143432
the macrophage-specific promoter mfap4 allows live, long-term analysis of macrophage behavior during mycobacterial infection in zebrafish.transgenic labeling of innate immune cell lineages within the larval zebrafish allows for real-time, in vivo analyses of microbial pathogenesis within a vertebrate host. to date, labeling of zebrafish macrophages has been relatively limited, with the most specific expression coming from the mpeg1 promoter. however, mpeg1 transcription at both endogenous and transgenic loci becomes attenuated in the presence of intracellular pathogens, including salmonella typhimurium and mycobacterium marinum. h ...201526445458
comparative sigma factor-mrna levels in mycobacterium marinum under stress conditions and during host infection.we have used rnaseq and qrt-pcr to study mrna levels for all σ-factors in different mycobacterium marinum strains under various growth and stress conditions. we also studied their levels in m. marinum from infected fish and mosquito larvae. the annotated σ-factors were expressed and transcripts varied in relation to growth and stress conditions. some were highly abundant such as siga, sigb, sigc, sigd, sige and sigh while others were not. the σ-factor mrna profiles were similar after heat stress ...201526445268
functional characterization of receptor-interacting serine/threonine kinase 2 (rip2) of the goldfish (carassius auratus l.).we report on the functional characterization of rip2 of the goldfish. quantitative expression analysis of goldfish rip2 revealed the greatest mrna levels in the spleen, monocytes and splenocytes. we generated a recombinant form of the molecule (rgrip2) and determined that anti-human rip2 polyclonal antibody specifically recognized recombinant goldfish rip2 (rgrip2). goldfish rip2 activity was inhibited by the p38 mapk pathway inhibitor sb203580. treatment of goldfish macrophages with lps, pgn, m ...201525242011
phylogenetic analysis of vitamin b12-related metabolism in mycobacterium tuberculosis.comparison of genome sequences from clinical isolates of mycobacterium tuberculosis with phylogenetically-related pathogens mycobacterium marinum, mycobacterium kansasii, and mycobacterium leprae reveals diversity amongst genes associated with vitamin b12-related metabolism. diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (snps) with predicted impact on protein function and transcriptional regulation. d ...201525988174
bacterial stimulation of toll-like receptor 4 drives macrophages to hemophagocytose.during acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype. salmonella enterica serovar typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. the mechanism(s) that triggers a macrophage to become hemophagocy ...201526459510
the caenorhabditis elegans p38 mapk gene plays a key role in protection from mycobacteria.mitogen-activated protein kinases (mapk) are critical mediators of cellular responses to pathogens and are activated in response to infection, but investigation is difficult in multi-cell hosts due to developmental lethality of mutations. mycobacterium marinum (mm) is an established model for tuberculosis, a disease afflicting nearly one-third of the world's population. we found that mm-infected caenorhabditis elegans display >80% mortality, but nonpathogenic m. smegmatis cause <15% mortality. c ...201626919641
inhibition of ifn-γ-induced nitric oxide dependent antimycobacterial activity by mir-155 and c/ebpβ.mir-155 (microrna-155) is an important non-coding rna in regulating host crucial biological regulators. however, its regulatory function in mycobacterium infection remains unclear. our study demonstrates that mir-155 expression is significantly increased in macrophages after mycobacterium marinum (m.m) infection. transfection with anti-mir-155 enhances nitric oxide (no) synthesis and decreases the mycobacterium burden, and vice versa, in interferon γ (ifn-γ) activated macrophages. more important ...201627070591
disseminated mycobacterium marinum infection with a destructive nasal lesion mimicking extranodal nk/t cell lymphoma: a case report.mycobacterium marinum is a ubiquitous waterborne organism that mainly causes skin infection in immunocompetent patients, and its disseminated infection is rare. extranodal nk/t cell lymphoma, nasal type (enkl) usually localizes at the nasal and/or paranasal area, but occasionally disseminates into the skin/soft tissue and gastrointestinal tract. compromised immunity is a risk factor for developing nontuberculous mycobacterial (ntm) infection and malignant lymphoma, and the 2 diseases may share s ...201626986167
chemical and antimicrobial profiling of propolis from different regions within libya.extracts from twelve samples of propolis collected from different regions of libya were tested for their activity against trypanosoma brucei, leishmania donovani, plasmodium falciparum, crithidia fasciculata and mycobacterium marinum and the cytotoxicity of the extracts was tested against mammalian cells. all the extracts were active to some degree against all of the protozoa and the mycobacterium, exhibiting a range of ec50 values between 1.65 and 53.6 μg/ml. the toxicity against mammalian cell ...201627195790
a microfluidic cell-trapping device for single-cell tracking of host-microbe interactions.the impact of cellular individuality on host-microbe interactions is increasingly appreciated but studying the temporal dynamics of single-cell behavior in this context remains technically challenging. here we present a microfluidic platform, infectchip, to trap motile infected cells for high-resolution time-lapse microscopy. this approach allows the direct visualization of all stages of infection, from bacterial uptake to death of the bacterium or host cell, over extended periods of time. we de ...201627425421
inibac induction is vitamin b12- and mutab-dependent in mycobacterium marinum.tuberculosis can be treated with a 6-month regimen of antibiotics. although the targets of most of the first-line antibiotics have been identified, less research has focused on the intrabacterial stress responses that follow upon treatment with antibiotics. studying the roles of these stress genes may lead to the identification of crucial stress-coping mechanisms that can provide additional drug targets to increase treatment efficacy. a three-gene operon with unknown function that is strongly up ...201627474746
mycobacteria in aquarium fish: results of a 3-year survey indicate caution required in handling pet-shop fish.fish are commonly infected with non-tuberculous mycobacteria (ntm), which should be regarded as potential pathogens when handling aquarium fish and equipment. this study examined 107 aquarium fish from pet shops. cultivation of the fish samples using different selective media was conducted for identification of ntm. isolates were identified using the genotype mycobacterium common mycobacteria and additional species assays, sequencing of the 16s rrna and rpob genes, and real-time pcr assay for id ...201627747884
inverse correlation between salt tolerance and host-adaptation in mycobacteria.the genus mycobacterium includes host-adapted organisms regarded as obligate and opportunistic pathogens and environmental organisms. factors contributing to this wide range of adaptations are poorly known.201627129386
[establishment of multiplex pcr method for rapid detection of nontuberculous mycobacteriums infection in the hand].to establish a multiplex polymerase chain reaction (mpcr) method with high sensitivity and specificity for rapid detection of common nontuberculous mycobacterium(ntm) infection in the hand.201627095780
nontuberculous mycobacterial disease in children - epidemiology, diagnosis & management at a tertiary center.there are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (ntm) disease in children.201626812154
nlpc/p60 domain-containing proteins of mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan.a subset of proteins containing nlpc/p60 domains are bacterial peptidoglycan hydrolases that cleave noncanonical peptide linkages and contribute to cell wall remodeling as well as cell separation during late stages of division. some of these proteins have been shown to cleave peptidoglycan in mycobacterium tuberculosis and play a role in mycobacterium marinum virulence of zebra fish; however, there are still significant knowledge gaps concerning the molecular function of these proteins in mycoba ...201626799947
in silico driven design and synthesis of rhodanine derivatives as novel antibacterials targeting the enoyl reductase inha.here, we report on the design, synthesis, and biological evaluation of 4-thiazolidinone (rhodanine) derivatives targeting mycobacterial tuberculosis (mtb) trans-2-enoyl-acyl carrier protein reductase (inha). compounds having bulky aromatic substituents at position 5 and a tryptophan residue at position n-3 of the rhodanine ring were the most active against inha, with ic50 values ranging from 2.7 to 30 μm. the experimental data showed consistent correlations with computational studies. their anti ...201626730986
the structure-antimicrobial activity relationships of a promising class of the compounds containing the n-arylpiperazine scaffold.this research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a n-arylpiperazine moiety. the in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. the molecules were screened against mycobacterium avium subsp. paratuberculosis cit03, m. smegmatis atcc 700084, m. kansasii dsm 44162, m. marinum camp 5644, staphylococcus aureus atcc 29213, methicillin-resistant s. aureus 63718, escher ...201627681720
zebrafish embryo disinfection with povidone-iodine: evaluating an alternative to chlorine bleach.mycobacteriosis is a common bacterial infection in laboratory zebrafish caused by several different species and strains of mycobacterium, including both rapid and slow growers. one control measure used to prevent mycobacterial spread within and between facilities is surface disinfection of eggs. recent studies have highlighted the effectiveness of povidone-iodine (pvpi) on preventing propagation of mycobacterium spp. found in zebrafish colonies. we evaluated the effect of disinfection using 12.5 ...201627351620
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
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
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
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
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
[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
mycobacterium marinum infection initially diagnosed as metastatic crohn's disease. 201625510444
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
exposure of mycobacterium marinum to low-shear modeled microgravity: effect on growth, the transcriptome and survival under stress.waterborne pathogenic mycobacteria can form biofilms, and certain species can cause hard-to-treat human lung infections. astronaut health could therefore be compromised if the spacecraft environment or water becomes contaminated with pathogenic mycobacteria. this work uses mycobacterium marinum to determine the physiological changes in a pathogenic mycobacteria grown under low-shear modeled microgravity (lsmmg). m. marinum were grown in high aspect ratio vessels (harvs) using a rotary cell cultu ...201628725743
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
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
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