Publications
2013
Kobayashi Taira, Ogawa Michinaga, Sanada Takahito, Mimuro Hitomi, Kim Minsoo, Ashida Hiroshi, Akakura Reiko, Yoshida Mitsutaka, Kawalec Magdalena, Reichhart Jean-Marc, Mizushima Tsunehiro, Sasakawa Chihiro
The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection Journal Article
In: Cell Host Microbe, vol. 13, no. 5, pp. 570–583, 2013, ISSN: 1934-6069.
Abstract | Links | BibTeX | Tags: Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors
@article{kobayashi_shigella_2013,
title = {The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection},
author = {Taira Kobayashi and Michinaga Ogawa and Takahito Sanada and Hitomi Mimuro and Minsoo Kim and Hiroshi Ashida and Reiko Akakura and Mitsutaka Yoshida and Magdalena Kawalec and Jean-Marc Reichhart and Tsunehiro Mizushima and Chihiro Sasakawa},
doi = {10.1016/j.chom.2013.04.012},
issn = {1934-6069},
year = {2013},
date = {2013-05-01},
journal = {Cell Host Microbe},
volume = {13},
number = {5},
pages = {570--583},
abstract = {Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.},
keywords = {Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors},
pubstate = {published},
tppubtype = {article}
}
2011
Limmer Stefanie, Haller Samantha, Drenkard Eliana, Lee Janice, Yu Shen, Kocks Christine, Ausubel Frederick M, Ferrandon Dominique
Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model Journal Article
In: Proc. Natl. Acad. Sci. U.S.A., vol. 108, no. 42, pp. 17378–17383, 2011, ISSN: 1091-6490.
Abstract | Links | BibTeX | Tags: Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence
@article{limmer_pseudomonas_2011b,
title = {Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model},
author = {Stefanie Limmer and Samantha Haller and Eliana Drenkard and Janice Lee and Shen Yu and Christine Kocks and Frederick M Ausubel and Dominique Ferrandon},
doi = {10.1073/pnas.1114907108},
issn = {1091-6490},
year = {2011},
date = {2011-10-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {108},
number = {42},
pages = {17378--17383},
abstract = {An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.},
keywords = {Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence},
pubstate = {published},
tppubtype = {article}
}
1989
Reichhart Jean-Marc, Essrich M, Dimarcq Jean-Luc, Hoffmann Danièle, Hoffmann Jules A, Lagueux Marie
Insect immunity. Isolation of cDNA clones corresponding to diptericin, an inducible antibacterial peptide from Phormia terranovae (Diptera). Transcriptional profiles during immunization Journal Article
In: Eur. J. Biochem., vol. 182, no. 2, pp. 423–427, 1989, ISSN: 0014-2956.
Abstract | BibTeX | Tags: Animals, Anti-Bacterial Agents, Bacterial Proteins, Base Sequence, Blotting, Diptera, DNA, Endoribonucleases, Enterobacter, Enterobacteriaceae, Gene Expression Regulation, Genes, Genetic, hoffmann, Insect Hormones, Insect Proteins, M3i, messenger, MHC Class II, Northern, reichhart, Ribonuclease H, RNA, Transcription
@article{reichhart_insect_1989,
title = {Insect immunity. Isolation of cDNA clones corresponding to diptericin, an inducible antibacterial peptide from Phormia terranovae (Diptera). Transcriptional profiles during immunization},
author = {Jean-Marc Reichhart and M Essrich and Jean-Luc Dimarcq and Danièle Hoffmann and Jules A Hoffmann and Marie Lagueux},
issn = {0014-2956},
year = {1989},
date = {1989-01-01},
journal = {Eur. J. Biochem.},
volume = {182},
number = {2},
pages = {423--427},
abstract = {We have previously isolated and characterized a family of novel 8-kDa cationic antibacterial peptides synthesized by larvae of Phormia terranovae (Diptera) in response to various injuries. These molecules have been named diptericins. The peptide sequence of diptericin A was used to prepare oligonucleotides for screening cDNA libraries and we report in the present paper the isolation of several cDNA clones encoding diptericin. The analysis of the nucleotide sequences indicates that diptericin is synthesized as a prepeptide which is matured in two steps: (a) cleavage of a signal peptide and (b) amidation of the C-terminal residue. Interestingly, the 3' untranslated region of the mRNA contains a consensus sequence TTATTTAT which is also observed in the mRNA of another insect antibacterial peptide (attacin-related sarcotoxin IIA) and in mRNAs encoding proteins related to the inflammatory response in mammals. Our data illustrate that diptericins form a polymorphic family of immune peptides. The transcription of the diptericin genes is rapidly induced in the fat body after inoculation of bacteria, as evidenced by the transcriptional profile.},
keywords = {Animals, Anti-Bacterial Agents, Bacterial Proteins, Base Sequence, Blotting, Diptera, DNA, Endoribonucleases, Enterobacter, Enterobacteriaceae, Gene Expression Regulation, Genes, Genetic, hoffmann, Insect Hormones, Insect Proteins, M3i, messenger, MHC Class II, Northern, reichhart, Ribonuclease H, RNA, Transcription},
pubstate = {published},
tppubtype = {article}
}