A novel vertebrate model of<i>Staphylococcus aureus</i>infection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens

Prajsnar, Tomasz K.; Cunliffe, Vincent T.; Foster, Simon J.; Renshaw, Stephen A.

doi:10.1111/j.1462-5822.2008.01213.x

Cited by 177 publications

(225 citation statements)

References 71 publications

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“…Intriguingly, several studies with zebrafish larvae have suggested that commensal microbiota colonize the larvae as soon as they hatch, but all assign great importance to the role played by gut microbiota in modifying innate immunity, nutrient metabolism, impaired intestinal differentiation, and function when microbes invade the internal organs (19, 22, 36-38, 40, 53). Also, in contrast to our work, it previously was proposed that host defense mechanisms, such as proinflammatory cytokines, are inducible mostly upon recognition of virulence factors of pathogenic bacteria (9,52,(54)(55)(56). However, it should be noted that spontaneous infection was not recorded in the present study; thus the "inflammatory state" observed in CONR fish was transient, rapidly returning to basal levels, marked here by the levels of IL-1β expression similar to those observed in the GF fish 24 h later (i.e., at 96 hpf).…”

Section: Discussioncontrasting

confidence: 49%

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Galindo-Villegas

García‐Moreno

Oliveira

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

204

161

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How fish larvae are protected from infection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germfree model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immune mediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.epigenetic | cytokines | evolution | gene regulation | live imaging

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Section: Discussioncontrasting

confidence: 49%

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Galindo-Villegas

García‐Moreno

Oliveira

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

204

161

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“…The increasing success of this alternative vertebrate model relies on major and unique opportunities that motivated and validated its use for a better understanding of numerous viral and bacterial infections 19,22,23,24,25,26,27,28,29 . As opposed to most other animal models, zebrafish embryos are optically transparent, allowing non-invasive fluorescence imaging 30 .…”

Section: Introductionmentioning

confidence: 99%

Deciphering and Imaging Pathogenesis and Cording of <em>Mycobacterium abscessus</em> in Zebrafish Embryos

Bernut

Dupont

Sahuquet

et al. 2015

JoVE

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Zebrafish (Danio rerio) embryos are increasingly used as an infection model to study the function of the vertebrate innate immune system in host-pathogen interactions. The ease of obtaining large numbers of embryos, their accessibility due to external development, their optical transparency as well as the availability of a wide panoply of genetic/immunological tools and transgenic reporter line collections, contribute to the versatility of this model. In this respect, the present manuscript describes the use of zebrafish as an in vivo model system to investigate the chronology of Mycobacterium abscessus infection. This human pathogen can exist either as smooth (S) or rough (R) variants, depending on cell wall composition, and their respective virulence can be imaged and compared in zebrafish embryos and larvae. Micro-injection of either S or R fluorescent variants directly in the blood circulation via the caudal vein, leads to chronic or acute/lethal infections, respectively. This biological system allows high resolution visualization and analysis of the role of mycobacterial cording in promoting abscess formation. In addition, the use of fluorescent bacteria along with transgenic zebrafish lines harbouring fluorescent macrophages produces a unique opportunity for multi-color imaging of the host-pathogen interactions. This article describes detailed protocols for the preparation of homogenous M. abscessus inoculum and for intravenous injection of zebrafish embryos for subsequent fluorescence imaging of the interaction with macrophages. These techniques open the avenue to future investigations involving mutants defective in cord formation and are dedicated to understand how this impacts on M. abscessus pathogenicity in a whole vertebrate. Video LinkThe video component of this article can be found at

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“…The zebrafish (ZF) is rapidly gaining favor as a useful model for the study of host-bacterial interactions (19)(20)(21)(22)(23)(24)(25). Because of its genetic tractability and optical transparency, ZF embryos represent an exquisite model to study many aspects of infectious diseases.…”

mentioning

confidence: 99%

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

Bernut

Herrmann

Kissa

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

302

493

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Mycobacterium abscessus is a rapidly growing Mycobacterium causing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. The M. abscessus rough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth (S) variant, but the underlying mechanisms of R-variant virulence remain obscure. Exploiting the optical transparency of zebrafish embryos, we observed that the increased virulence of the M. abscessus R variant compared with the S variant correlated with the loss of GPL production. The virulence of the R variant involved the massive production of serpentine cords, absent during S-variant infection, and the cords initiated abscess formation leading to rapid larval death. Cording occurred within the vasculature and was highly pronounced in the central nervous system (CNS). It appears that M. abscessus is transported to the CNS within macrophages. The release of M. abscessus from apoptotic macrophages initiated the formation of cords that grew too large to be phagocytized by macrophages or neutrophils. This study is a description of the crucial role of cording in the in vivo physiopathology of M. abscessus infection and emphasizes cording as a mechanism of immune evasion.morphotype | pathogenesis | granuloma | innate immunity T he rapidly growing mycobacterium (RGM) Mycobacterium abscessus (M. abscessus) is an emerging pathogen that infects a wide spectrum of tissues in humans, including lungs, skin, and soft tissues (1, 2). M. abscessus lung disease is highly prevalent in patients with cystic fibrosis (CF) and is becoming a major issue for most CF centers worldwide (3-6). Although M. abscessus is an RGM, it can persist and cause lung disease with caseous lesions (7).M. abscessus exists as two variants: rough (R) and smooth (S). Ex vivo and in vivo studies have described the hypervirulence phenotype of the R versus the S morphotype (8, 9), and epidemiological studies have confirmed the persistence and acute respiratory syndromes caused by the R morphotype (4, 10, 11). The major difference between the R and S variants is the loss of a surface-associated glycopeptidolipid (GPL) (12). Analysis of the pathogenicity of M. abscessus has been hampered by the lack of genetic tools and the restricted panel of cellular/animal models. However, new genetic tools, including conditional gene expression, recently have been applied to both the S and R morphotypes (13, 14), but developing new animal models amenable to the manipulation of the host response is still challenging. The M. abscessus genome harbors a mercury-resistance plasmid sharing 99% identity with an episome from the slowgrowing fish pathogen Mycobacterium marinum, indicating that these species have exchanged this plasmid in a shared ecosystem (15). M. abscessus has been described in wild and captive fish species (16,17), and hand infections caused by M. abscessus have been reported in healthy fish handlers (18), sug...

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A novel vertebrate model ofStaphylococcus aureusinfection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens

Cited by 177 publications

References 71 publications

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Deciphering and Imaging Pathogenesis and Cording of <em>Mycobacterium abscessus</em> in Zebrafish Embryos

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

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