Evolution of the Zebrafish Model: From Development to Immunity and Infectious Disease

Phelps, Hilary A.; Neely, Melody N.

doi:10.1089/zeb.2005.2.87

Cited by 77 publications

(57 citation statements)

References 117 publications

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“…Autolysin also plays crucial roles in the pathogenesis of pneumococcal meningitis (24). In the last few years, zebrafish has been used as a model for human disease, cancer and immunological studies, and some experimental infections have been conducted with several streptococcal species such as Streptococcus iniae, S. pyogenes (34,38), and Streptococcus agalactiae (40). The fact that zebrafish have adaptive and innate cellular immune defenses that are not unlike those of the mammalian species most often used to model infectious diseases of humans (52) makes them highly useful as a model host organism.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Functional Analysis of atl , a Novel Gene Encoding Autolysin in Streptococcus suis

Chen

2012

J Bacteriol

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Streptococcus suis serotype 2 (S. suis 2) is an important swine and human pathogen responsible for septicemia and meningitis. A novel gene, designated atl and encoding a major autolysin of S. suis 2 virulent strain HA9801, was identified and characterized in this study. The Atl protein contains 1,025 amino acids with a predicted molecular mass of 113 kDa and has a conserved N-acetylmuramoyl-L-alanine amidase domain. Recombinant Atl was expressed in Escherichia coli, and its bacteriolytic and fibronectin-binding activities were confirmed by zymography and Western affinity blotting. Two bacteriolytic bands were shown in the sodium dodecyl sulfate extracts of HA9801, while both were absent from the atl inactivated mutant. Cell chains of the mutant strain became longer than that of the parental strain. In the autolysis assay, HA9801 decreased to 20% of the initial optical density (OD) value, while the mutant strain had almost no autolytic activity. The biofilm capacity of the atl mutant was reduced ϳ30% compared to the parental strain. In the zebrafish infection model, the 50% lethal dose of the mutant strain was increased up to 5-fold. Furthermore, the adherence to HEp-2 cells of the atl mutant was 50% less than that of the parental strain. Based on the functional analysis of the recombinant Atl and observed effects of atl inactivation on HA9801, we conclude that Atl is a major autolysin of HA9801. It takes part in cell autolysis, separation of daughter cells, biofilm formation, fibronectinbinding activity, cell adhesion, and pathogenesis of HA9801. Bacteria produce several peptidoglycan hydrolases, some of which are autolysins able to disintegrate their own peptidoglycan saccules and lead to bacterial cell lysis in unfavorable conditions (44). Autolysins have been implicated in various biological functions, such as cell wall turnover, cell separation, cell division and antibiotic-induced autolysis (48,55). In addition to their biological functions, bacterial autolysins are also involved or implicated in the pathogenicity of Gram-positive bacteria. Intact autolytic function is required for full virulence in Streptococcus pneumoniae (7). Autolysin-deficient mutants, including a LytA mutant of S. pneumoniae (8), an AtlE mutant of Staphylococcus epidermidis (46), and Ami (36), Auto (11), p60 (41), and MurA (28) mutants of Listeria monocytogenes are less virulent in animal models than their parental strains.Streptococcus suis is an important zoonotic pathogen that causes a variety of serious diseases, including meningitis, arthritis, and septicemia and even sudden death in pigs and humans (35,49). Among the 35 serotypes of S. suis that have been described, S. suis serotype 2 (S. suis 2) is the most virulent and most frequently isolated serotype. Although a set of virulence factors have been identified, the pathogenic mechanisms of S. suis 2 are still unclear. Autolysins are believed to play an important role in cell wall metabolism and in the pathogenicity of bacteria (7). However, the concentration of autolysins in S....

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Section: Discussionmentioning

confidence: 99%

Characterization and Functional Analysis of atl , a Novel Gene Encoding Autolysin in Streptococcus suis

Chen

2012

J Bacteriol

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“…Zebrafish is an increasingly popular model organism for studying host-pathogen interactions and immunity (1,37,38,47,53,54,55). To further develop the potential of zebrafish as a model for inflammatory processes and infectious disease, it is necessary to know whether IL-1␤ activity is regulated at the level of proteolytic processing and, if so, whether a caspase 1 ortholog is responsible.…”

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confidence: 99%

Roles of Inflammatory Caspases during Processing of Zebrafish Interleukin-1β in Francisella noatunensis Infection

et al. 2012

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The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1␤) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1␤ is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1␤. Although zebrafish encode orthologs of IL-1␤ and inflammatory caspases, the processing of IL-1␤ by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1␤ processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1␤ processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1␤ into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1␤, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1␤ in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.

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“…In recent years many infection systems for zebrafish have been developed (35)(36)(37). In this paper we used S. typhimurium as a case study for Gram-negative infections.…”

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confidence: 99%

Transcriptome Profiling and Functional Analyses of the Zebrafish Embryonic Innate Immune Response to Salmonella Infection

Stockhammer

Zakrzewska

Hegedűs

et al. 2009

The Journal of Immunology

197

204

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Due to the clear separation of innate immunity from adaptive responses, the externally developing zebrafish embryo represents a useful in vivo model for identification of innate host determinants of the response to bacterial infection. Here we performed a time-course transcriptome profiling study and gene ontology analysis of the embryonic innate immune response to infection with two model Salmonella strains that elicit either a lethal infection or an attenuated response. The transcriptional response to infection with both the lethal strain and the avirulent LPS O-Ag mutant strain showed clear conservation with host responses detected in other vertebrate models and human cells, including induction of genes encoding cell surface receptors, signaling intermediates, transcription factors, and inflammatory mediators. Furthermore, our study led to the identification of a large set of novel immune response genes and infection markers, the future functional characterization of which will support vertebrate genome annotation. From the time series and bacterial strain comparisons, matrix metalloproteinase genes, including mmp9, were among the most consistent infection-responsive genes. Purified Salmonella flagellin also strongly induced mmp9 expression. Using knockdown analysis, we showed that this gene was downstream of the zebrafish homologs of the flagellin receptor TLR5 and the adaptor MyD88. Additionally, flagellin-mediated induction of other inflammation markers, including il1b, il8, and cxcl-C1c, was reduced upon Tlr5 knockdown as well as expression of irak3, a putative negative TLR pathway regulator. Finally, we showed that induction of il1b, mmp9, and irak3 requires Myd88-dependent signaling, while ifn1 and il8 were induced Myd88 independently during Salmonella infection.

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Evolution of the Zebrafish Model: From Development to Immunity and Infectious Disease

Cited by 77 publications

References 117 publications

Characterization and Functional Analysis of atl , a Novel Gene Encoding Autolysin in Streptococcus suis

Characterization and Functional Analysis of atl , a Novel Gene Encoding Autolysin in Streptococcus suis

Roles of Inflammatory Caspases during Processing of Zebrafish Interleukin-1β in Francisella noatunensis Infection

Transcriptome Profiling and Functional Analyses of the Zebrafish Embryonic Innate Immune Response to Salmonella Infection

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