Genomes and Genes
Gene Symbol: Mtk
Alias: BcDNA:RH07954, CG8175, DIM 17, Dmel\CG8175, METCH, Metc, Metch, metch, metk, mtk, metchnikowin, CG8175-PA, Mtk-PA, drosophila immune induced molecule 17, metchikowin, metchinkowin, metchnikovin, metchnikowin A, metchnikowin B, metchnikowin precursor, metchnikowin-1, metchnikowin-2, metchnikowine
Species: fruit fly
- Levashina E, Ohresser S, Bulet P, Reichhart J, Hetru C, Hoffmann J. Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties. Eur J Biochem. 1995;233:694-700 pubmed..The novel peptide, which we propose to name metchnikowin, is a member of a family of proline-rich peptides, and we discuss the possible evolutionary relationships ..
- Leulier F, Rodriguez A, Khush R, Abrams J, Lemaitre B. The Drosophila caspase Dredd is required to resist gram-negative bacterial infection. EMBO Rep. 2000;1:353-8 pubmed
- Marek L, Kagan J. Phosphoinositide binding by the Toll adaptor dMyD88 controls antibacterial responses in Drosophila. Immunity. 2012;36:612-22 pubmed publisher..We therefore propose that dMyD88 is the functional homolog of TIRAP and that both proteins function as sorting adaptors to recruit downstream signaling adaptors to activated receptors. ..
- Hallem E, Rengarajan M, Ciche T, Sternberg P. Nematodes, bacteria, and flies: a tripartite model for nematode parasitism. Curr Biol. 2007;17:898-904 pubmed
- Tang H, Kambris Z, Lemaitre B, Hashimoto C. A serpin that regulates immune melanization in the respiratory system of Drosophila. Dev Cell. 2008;15:617-26 pubmed publisher..Such signaling between local and systemic immune responses could represent an alarm mechanism that prepares the host in case a pathogen breaches epithelial defenses to invade internal tissues. ..
- Zhang Z, Palli S. Identification of a cis-regulatory element required for 20-hydroxyecdysone enhancement of antimicrobial peptide gene expression in Drosophila melanogaster. Insect Mol Biol. 2009;18:595-605 pubmed publisher..peptidoglycan-induced expression of four other antimicrobial peptide (AMP) genes--drosomycin, attacin-A, metchnikowin and cecropin A1...
- Georgel P, Naitza S, Kappler C, Ferrandon D, Zachary D, Swimmer C, et al. Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis. Dev Cell. 2001;1:503-14 pubmed..We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila. ..
- Vidal S, Khush R, Leulier F, Tzou P, Nakamura M, Lemaitre B. Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-kappaB-dependent innate immune responses. Genes Dev. 2001;15:1900-12 pubmed..Our genetic demonstration of dTAK1's role in the regulation of Drosophila antimicrobial peptide gene expression suggests an evolutionary conserved role for TAK1 in the activation of Rel/NF-kappaB-mediated host defense reactions. ..
- Levashina E, Ohresser S, Lemaitre B, Imler J. Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin. J Mol Biol. 1998;278:515-27 pubmedb>Metchnikowin is a recently discovered proline-rich peptide from Drosophila with antibacterial and antifungal properties. Like most other antimicrobial peptides from insects, its expression is immune-inducible...
- Lu Y, Wu L, Anderson K. The antibacterial arm of the drosophila innate immune response requires an IkappaB kinase. Genes Dev. 2001;15:104-10 pubmed..The ird5 gene encodes a Drosophila homolog of mammalian IkappaB kinases (IKKs). The ird5 phenotype and sequence suggest that the gene is specifically required for the activation of Relish, a Drosophila NF-kappaB family member. ..
- Rutschmann S, Jung A, Hetru C, Reichhart J, Hoffmann J, Ferrandon D. The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila. Immunity. 2000;12:569-80 pubmed..We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals. ..
- Seong K, Kim C, Lee B, Nam S, Yang K, Kim J, et al. Low-dose radiation induces Drosophila innate immunity through Toll pathway activation. J Radiat Res. 2012;53:242-9 pubmed..These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila. ..
- Shin S, Kokoza V, Bian G, Cheon H, Kim Y, Raikhel A. REL1, a homologue of Drosophila dorsal, regulates toll antifungal immune pathway in the female mosquito Aedes aegypti. J Biol Chem. 2005;280:16499-507 pubmed..bassiana. These results indicate that the homologue of Dl, but not that of Dif, is a key regulator of the Toll antifungal immune pathway in A. aegypti female mosquitoes. ..
- Uttenweiler Joseph S, Moniatte M, Lagueux M, Van Dorsselaer A, Hoffmann J, Bulet P. Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study. Proc Natl Acad Sci U S A. 1998;95:11342-7 pubmed..Finally, molecular cloning and Northern blot analyses revealed that one of the DIMs is produced as a prepropeptide and is inducible on a bacterial challenge. ..
- Tzou P, Ohresser S, Ferrandon D, Capovilla M, Reichhart J, Lemaitre B, et al. Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity. 2000;13:737-48 pubmed
- Lemaitre B, Reichhart J, Hoffmann J. Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc Natl Acad Sci U S A. 1997;94:14614-9 pubmed..This response is mediated through the selective activation of the Toll pathway. ..
- Lazzaro B, Sceurman B, Clark A. Genetic basis of natural variation in D. melanogaster antibacterial immunity. Science. 2004;303:1873-6 pubmed..Variation in these genes, therefore, seems to drive variability in immunocompetence among wild Drosophila. ..
- Zambon R, Nandakumar M, Vakharia V, Wu L. The Toll pathway is important for an antiviral response in Drosophila. Proc Natl Acad Sci U S A. 2005;102:7257-62 pubmed..Additionally, our results demonstrate the validity of using a genetic approach to identify genes and pathways used in viral innate immune responses in Drosophila...
- Brennan C, Delaney J, Schneider D, Anderson K. Psidin is required in Drosophila blood cells for both phagocytic degradation and immune activation of the fat body. Curr Biol. 2007;17:67-72 pubmed..These data establish a role for the phagocytic blood cells of Drosophila in detection of infection and activation of the humoral immune response. ..
- Becker T, Loch G, Beyer M, Zinke I, Aschenbrenner A, Carrera P, et al. FOXO-dependent regulation of innate immune homeostasis. Nature. 2010;463:369-73 pubmed publisher..The sparse production of AMPs in epithelial tissues in response to FOXO may help modulating the defence reaction without harming the host tissues, in particular when animals are suffering from energy shortage or stress. ..
- Kleino A, Myllymäki H, Kallio J, Vanha aho L, Oksanen K, Ulvila J, et al. Pirk is a negative regulator of the Drosophila Imd pathway. J Immunol. 2008;180:5413-22 pubmed..Furthermore, pirk-overexpressing flies were more susceptible to Gram-negative bacterial infection than wild-type flies. We conclude that Pirk is a negative regulator of the Imd pathway. ..
- Flatt T, Heyland A, Rus F, Porpiglia E, Sherlock C, Yamamoto R, et al. Hormonal regulation of the humoral innate immune response in Drosophila melanogaster. J Exp Biol. 2008;211:2712-24 pubmed publisher..Our results suggest that 20E and JH play major roles in the regulation of gene expression in response to immune challenge. ..
- Braun A, Hoffmann J, Meister M. Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes. Proc Natl Acad Sci U S A. 1998;95:14337-42 pubmed..By working in synergy, they provide Drosophila a highly effective defense against injury and/or infection...
- Costa A, Jan E, Sarnow P, Schneider D. The Imd pathway is involved in antiviral immune responses in Drosophila. PLoS ONE. 2009;4:e7436 pubmed publisher..Our data show that antiviral innate immune responses in flies infected with CrPV depend upon hemocytes and signaling through the Imd pathway. ..
- Delaney J, Stoven S, Uvell H, Anderson K, Engstrom Y, Mlodzik M. Cooperative control of Drosophila immune responses by the JNK and NF-kappaB signaling pathways. EMBO J. 2006;25:3068-77 pubmed..Our data indicate that dTAK1 is not required for Relish activation, but instead is required in JNK signaling for antimicrobial peptide gene expression. ..
- Kim L, Choi U, Cho H, Lee J, Lee W, Kim J, et al. Down-regulation of NF-kappaB target genes by the AP-1 and STAT complex during the innate immune response in Drosophila. PLoS Biol. 2007;5:e238 pubmed..We conclude that an inhibitory effect of AP-1 and STAT on NF-kappaB is required for properly balanced immune responses and appears to be evolutionarily conserved. ..
- Choe K, Werner T, Stoven S, Hultmark D, Anderson K. Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science. 2002;296:359-62 pubmed
- Senger K, Armstrong G, Rowell W, Kwan J, Markstein M, Levine M. Immunity regulatory DNAs share common organizational features in Drosophila. Mol Cell. 2004;13:19-32 pubmed..Aspects of this "regulatory code" are essential for the immune response. These results suggest that immunity regulatory DNAs contain constrained organizational features, which may be a general property of eukaryotic enhancers. ..
- Stergiopoulos K, Cabrero P, Davies S, Dow J. Salty dog, an SLC5 symporter, modulates Drosophila response to salt stress. Physiol Genomics. 2009;37:1-11 pubmed publisher..Accordingly, CG2196 was renamed salty dog (salt). ..
- Wang Z, Berkey C, Watnick P. The Drosophila protein mustard tailors the innate immune response activated by the immune deficiency pathway. J Immunol. 2012;188:3993-4000 pubmed publisher..Mtd homologs have been implicated in resistance to oxidative stress. However, to our knowledge this is the first evidence that Mtd or its homologs alter the output of an innate immunity signaling cascade from within the nucleus...
- Oh C, Moon C, Jeong M, Kwon S, Jang J. Drosophila melanogaster model for Mycobacterium abscessus infection. Microbes Infect. 2013;15:788-95 pubmed publisher..To the best of our knowledge, this is the first report that mycobacteria induce the production of antimicrobial peptides in D. melanogaster. ..
- Marshall K, Sinclair B. Repeated stress exposure results in a survival-reproduction trade-off in Drosophila melanogaster. Proc Biol Sci. 2010;277:963-9 pubmed publisher..Given that many environments are not static, this trade-off indicates that investigating the effects of repeated stress exposure is important for understanding and predicting physiological responses in the wild. ..
- Levashina E, Langley E, Green C, Gubb D, Ashburner M, Hoffmann J, et al. Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila. Science. 1999;285:1917-9 pubmed..Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense...
- Winterhalter W, Fedorka K. Sex-specific variation in the emphasis, inducibility and timing of the post-mating immune response in Drosophila melanogaster. Proc Biol Sci. 2009;276:1109-17 pubmed publisher..Our results suggest that variation in the effectiveness of the immune response between the sexes may be driven by differences in emphasis rather than overall investment. ..
- Tsuzuki S, Matsumoto H, Furihata S, Ryuda M, Tanaka H, Sung E, et al. Switching between humoral and cellular immune responses in Drosophila is guided by the cytokine GBP. Nat Commun. 2014;5:4628 pubmed publisher..Thus, we describe mechanisms to initiate immune programs that are either humoral or cellular in nature, but not both; such immunophysiological polarization may minimize homeostatic imbalance during infection. ..
- Sun X, Wheeler C, Yolitz J, Laslo M, Alberico T, Sun Y, et al. A mitochondrial ATP synthase subunit interacts with TOR signaling to modulate protein homeostasis and lifespan in Drosophila. Cell Rep. 2014;8:1781-1792 pubmed publisher..Our data reveal a link among diet, mitochondria, and MAPK and TOR signaling in aging and stresses the importance of considering genetic background and diet composition in implementing interventions for promoting healthy aging. ..
- Park S, Heo Y, Kim K, Cho Y. Drosophila melanogaster is susceptible to Vibrio cholerae infection. Mol Cells. 2005;20:409-15 pubmed..cholerae infection compared to V. vulnificus infection. Ectopic expression of Attacin A and Metchnikowin enhanced the survival of D. melanogaster upon V. cholerae infection...
- Furihata S, Matsumoto H, Kimura M, Hayakawa Y. Venom components of Asobara japonica impair cellular immune responses of host Drosophila melanogaster. Arch Insect Biochem Physiol. 2013;83:86-100 pubmed publisher..These results reveal that A. japonica venom toxicity allows exploitation of a broader range of host insects because it is essential to overcome cellular immune responses of the host for successful parasitism. ..
- Dushay M, Roethele J, Chaverri J, Dulek D, Syed S, Kitami T, et al. Two attacin antibacterial genes of Drosophila melanogaster. Gene. 2000;246:49-57 pubmed..We present a comparison of the promoter regions of the two attacin genes to those cloned from other antimicrobial peptide genes to assist a better understanding of how antimicrobial genes are differentially regulated. ..
- Tsuzuki S, Ochiai M, Matsumoto H, Kurata S, Ohnishi A, Hayakawa Y. Drosophila growth-blocking peptide-like factor mediates acute immune reactions during infectious and non-infectious stress. Sci Rep. 2012;2:210 pubmed publisher..These results indicate that the Drosophila GBP signaling pathway mediates acute innate immune reactions under various stresses, regardless of whether they are infectious or non-infectious. ..
- Thimgan M, Gottschalk L, Toedebusch C, McLeland J, Rechtschaffen A, Gilliland Roberts M, et al. Cross-translational studies in human and Drosophila identify markers of sleep loss. PLoS ONE. 2013;8:e61016 pubmed publisher..These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss. ..
- Ji S, Sun M, Zheng X, Li L, Sun L, Chen D, et al. Cell-surface localization of Pellino antagonizes Toll-mediated innate immune signalling by controlling MyD88 turnover in Drosophila. Nat Commun. 2014;5:3458 pubmed publisher..Collectively, our study uncovers a mechanism by which a feedback regulatory loop involving MyD88 and Pellino controls Toll-mediated signalling, thereby maintaining homeostasis of host innate immunity. ..
- Bitra K, Suderman R, Strand M. Polydnavirus Ank proteins bind NF-?B homodimers and inhibit processing of Relish. PLoS Pathog. 2012;8:e1002722 pubmed publisher..Overall, our data provide the first quantitative measures of insect and viral I?B binding affinities, while also showing that viral mimics disable Relish processing...
- Varma D, Bülow M, Pesch Y, Loch G, Hoch M. Forkhead, a new cross regulator of metabolism and innate immunity downstream of TOR in Drosophila. J Insect Physiol. 2014;69:80-8 pubmed publisher..the negative TOR regulators TSC1/TSC2, resulted in a specific induction of the AMPs Diptericin (Dpt) and Metchnikowin (Mtk). In contrast, overexpression of Rheb, which positively regulates TOR led to a repression of the two AMPs...
- Hamilos G, Samonis G, Kontoyiannis D. Recent Advances in the Use of Drosophila melanogaster as a Model to Study Immunopathogenesis of Medically Important Filamentous Fungi. Int J Microbiol. 2012;2012:583792 pubmed publisher..In view of recent advances in Drosophila genetics, fruit flies will become an invaluable surrogate model to study immunopathogenesis of fungal diseases. ..
- Rao X, Xu X, Yu X. Manduca sexta moricin promoter elements can increase promoter activities of Drosophila melanogaster antimicrobial peptide genes. Insect Biochem Mol Biol. 2011;41:982-92 pubmed publisher..These findings revealed an approach of engineering AMP genes with enhanced activities, which may lead to broad applications. ..
- Hill Burns E, Clark A. X-linked variation in immune response in Drosophila melanogaster. Genetics. 2009;183:1477-91 pubmed publisher..Many of the associations act in a sex-specific or sexually antagonistic manner, supporting the theory that with the selective pressures facing genes on the X chromosome, sexually antagonistic variation may be more easily maintained. ..
- Rahnamaeian M, Langen G, Imani J, Khalifa W, Altincicek B, von Wettstein D, et al. Insect peptide metchnikowin confers on barley a selective capacity for resistance to fungal ascomycetes pathogens. J Exp Bot. 2009;60:4105-14 pubmed publisherThe potential of metchnikowin, a 26-amino acid residue proline-rich antimicrobial peptide synthesized in the fat body of Drosophila melanogaster was explored to engineer disease resistance in barley against devastating fungal plant ..
- Sackton T, Clark A. Comparative profiling of the transcriptional response to infection in two species of Drosophila by short-read cDNA sequencing. BMC Genomics. 2009;10:259 pubmed publisher..virilis hemolymph and validate our transcriptional data. These results suggest that the acquisition of novel components of the immune system, and particularly novel effector proteins, may be a common evolutionary phenomenon. ..
- Fedorka K, Linder J, Winterhalter W, Promislow D. Post-mating disparity between potential and realized immune response in Drosophila melanogaster. Proc Biol Sci. 2007;274:1211-7 pubmed..Thus, estimates of immunity based on gene expression do not appear to reflect an actual ability to defend against pathogens in the hours following copulation. We discuss the possible mechanisms that may account for this pattern. ..
- Cao Y, Chtarbanova S, Petersen A, Ganetzky B. Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain. Proc Natl Acad Sci U S A. 2013;110:E1752-60 pubmed publisher..These results provide a mechanistic link between innate immune responses and neurodegeneration and may have important implications for the role of neuroinflammation in human neurodegenerative diseases as well...
- Hoffmann J, Kafatos F, Janeway C, Ezekowitz R. Phylogenetic perspectives in innate immunity. Science. 1999;284:1313-8 pubmed..In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity. ..
- Linder J, Owers K, Promislow D. The effects of temperature on host-pathogen interactions in D. melanogaster: who benefits?. J Insect Physiol. 2008;54:297-308 pubmed..The approach described here allows us to determine whether this effect is due primarily to temperature-specific effects on the host or on its pathogen. These results suggest that both may be important. ..
- Domanitskaya E, Liu H, Chen S, Kubli E. The hydroxyproline motif of male sex peptide elicits the innate immune response in Drosophila females. FEBS J. 2007;274:5659-68 pubmed..We suggest that SP acts by chemical mimicry of sugar components of the bacterial cell wall. Thus, SP may induce the immune system via pattern recognition receptors. ..
- Lazzaro B, Sackton T, Clark A. Genetic variation in Drosophila melanogaster resistance to infection: a comparison across bacteria. Genetics. 2006;174:1539-54 pubmed..lactis and E. faecalis, respectively, most of the molecular polymorphisms tested explain <10% of the total variance in bacterial load sustained after infection...
- Dissel S, Melnattur K, Shaw P. Sleep, Performance, and Memory in Flies. Curr Sleep Med Rep. 2015;1:47-54 pubmed publisher..We conclude that as Drosophila sleep researchers expand their analysis beyond sleep time, the opportunities to discover the function of sleep will be enhanced. ..
- Helenius I, Haake R, Kwon Y, Hu J, Krupinski T, Casalino Matsuda S, et al. Identification of Drosophila Zfh2 as a Mediator of Hypercapnic Immune Regulation by a Genome-Wide RNA Interference Screen. J Immunol. 2016;196:655-667 pubmed publisher..Taken together, to our knowledge, these results identify Zfh2 as the first in vivo mediator of hypercapnic immune suppression. ..
- Yagi Y, Nishida Y, Ip Y. Functional analysis of Toll-related genes in Drosophila. Dev Growth Differ. 2010;52:771-83 pubmed publisher..Overall our results suggest that some of the Toll-related proteins, such as 18W, Toll-7 and Toll-8, may have redundant functions in regulating developmental processes. ..
- Reed D, Huang X, Wohlschlegel J, Levine M, Senger K. DEAF-1 regulates immunity gene expression in Drosophila. Proc Natl Acad Sci U S A. 2008;105:8351-6 pubmed publisher..immune response and is specifically important for the induction of two genes encoding antimicrobial peptides, Metchnikowin (Mtk) and Drosomycin (Drs)...
- Ligoxygakis P, Bulet P, Reichhart J. Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila. EMBO Rep. 2002;3:666-73 pubmed..18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria. ..
- Hedengren M, Borge K, Hultmark D. Expression and evolution of the Drosophila attacin/diptericin gene family. Biochem Biophys Res Commun. 2000;279:574-81 pubmed..This induction is reduced in imd mutants, and unexpectedly also in Tl(-) mutants. The 18w mutation particularly affects the induction of AttC, which may be a useful marker for 18w signaling. ..