Molecular basis and evolutionary dynamics of C. elegans-microbiota interactions

The model nematode Caenorhabditis elegans is associated with a distinct microbial community under natural conditions. Yet, to date, the role of the worm’s microbiota for life history functions and evolutionary fitness is largely unexplored. This collaborative project aims at providing a holistic understanding of C. elegans-microbiota interactions by
(i) dissecting the influence of the microbiota in mediating evolutionary adaptation to environmental stress using experimental evolution;
(ii) analysing the underlying genetics of C. elegans-microbiota interactions through QTL analysis, transcriptomics and functional genetic manipulation;
(iii) assessing the particular role of bioactive peptides and hydrolytic enzymes in shaping the nematode’s microbial associations using genetic and protein-level analyses; and
(iv) characterizing the proteomic basis of the interaction with the help of state-of-the-art proteome analysis techniques.

The proposed work is based on several advantages of the nematode as an experimental system, including the possibility of producing sterile nematodes through routine procedure combined with controlled re-infection experiments. The nematode also allows efficient performance of evolution experiments because of its short generation time and its amenability to cryopreservation for later analyses. Moreover, a versatile toolbox for genetic manipulation and comprehensive genome databases facilitate the cross-level “omics” analysis of C. elegans-microbiota interactions.

Overall, our project is unique in that it uses complementary study approaches and a highly efficient experimental model system to provide a holistic view on host-microbiota interactions that encompasses the involved evolutionary dynamics as well as the underlying processes at genomic, genetic, transcriptomic, proteomic and also biochemical levels. Based on such a cross-disciplinary analysis approach, our results are expected to yield novel insights into how the microbiota affects evolutionary change and how such dynamics are realized at the molecular level.


Julia Johnke

PhD Candidate, Associated Junior Researcher
Kiel University Zoological Institute

Dr. Liam Cassidy

Postdoctoral Researcher
Kiel University Institute for Experimental Medicine

Dr. Carola Petersen

Postdoctoral Researcher, Associated Junior Researcher
Kiel University Zoological Institute



A novel tertiary prep-HPLC method for the isolation of single amino acids for AMS-radiocarbon measurement.

Fernandes R, Koudelka T, Tholey A, Dreves A (2017); J Chromatogr B Analyt Technol Biomed Life Sci., 1058:85-92. doi: 10.1016/j.jchromb.2017.05.017

FeaturedAlternative evolutionary paths to bacterial antibiotic resistance cause distinct collateral effects.

Barbosa C, Trebosc V, Kemmer C, Rosenstiel P, Beardmore R, Schulenburg H, Jansen G (2017); Mol Biol Evol., doi: 10.1093/molbev/msx158

Adhesion forces and mechanics in mannose-mediated acanthamoeba interactions.

Huth S, Reverey J F, Leippe M, Selhuber-Unkel C (2017); PLoS One., 12(5):e0176207. doi: 10.1371/journal.pone.0176207

The Natural Biotic Environment of Caenorhabditis elegans.

Schulenburg H, Félix M A (2017); Genetics., 206(1):55-86. doi: 10.1534/genetics.116.195511

Highly potent host external immunity acts as a strong selective force enhancing rapid parasite virulence evolution.

Rafaluk C, Yang W, Mitschke A, Rosenstiel P, Schulenburg H, Joop G (2017); Environ Microbiol., 19(5):2090-2100. doi: 10.1111/1462-2920.13736

Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae.

Greenwood J M, Milutinović B, Peuß R, Behrens S, Esser D, Rosenstiel P, Schulenburg H, Kurtz J (2017); BMC Genomics., 18(1):329. doi: 10.1186/s12864-017-3705-7

Multiplexed Protease Specificity Profiling Using Isobaric Labeling.

Tucher J, Tholey A (2017); Methods Mol Biol., 1574:171-182. doi: 10.1007/978-1-4939-6850-3_12

Meprin Metalloproteases Generate Biologically Active Soluble Interleukin-6 Receptor to Induce Trans-Signaling.

Arnold P, Boll I, Rothaug M, Schumacher N, Schmidt F, Wichert R, Schneppenheim J, Lokau J, Pickhinke U, Koudelka T, Tholey A, Rabe B, Scheller J, Lucius R, Garbers C, Rose-John S, Becker-Pauly C (2017); Sci Rep., 7:44053. doi: 10.1038/srep44053

Caenorhabditis elegans as a model for microbiome research.

Zhang F, Berg M, Dierking K, Félix M A, Shapira M, Samuel B, Schulenburg H (2017); Front. Microbiol., 8:485. doi: 10.3389/fmicb.2017.00485

Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection. Gastroenterology.

Ott S J, Waetzig G H, Rehman A, Moltzau-Anderson J, Bharti R, Grasis J A, Cassidy L, Tholey A, Fickenscher H, Seegert D, Rosenstiel P, Schreiber S (2017); Gastroenterology, 152(4):799-811.e7. doi: 10.1053/j.gastro.2016.11.010

Reduction of GAPDH in lenses of Parkinson’s disease patients: A possible new biomarker.

Klettner A, Tholey A, Wiegandt A, Richert E, Nölle B, Deuschl G, Roider J, Schneider S A (2017); Mov Disord., 32(3):459-462. doi: 10.1002/mds.26863

Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin β and promotes transendothelial cell migration.

Bedau T, Peters F, Prox J, Arnold P, Schmidt F, Finkernagel M, Köllmann S, Wichert R, Otte A, Ohler A, Stirnberg M, Lucius R, Koudelka T, Tholey A, Biasin V, Pietrzik C U, Kwapiszewska G, Becker-Pauly C (2017); FASEB J., 31(3):1226-1237. doi: 10.1096/fj.201601113R

Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role of N-Glycosylation.

Riethmueller S, Somasundaram P, Ehlers J C, Hung C W, Flynn C M, Lokau J, Agthe M, Düsterhöft S, Zhu Y, Grötzinger J, Lorenzen I, Koudelka T, Yamamoto K, Pickhinke U, Wichert R, Becker-Pauly C, Rädisch M, Albrecht A, Hessefort M, Stahnke D, Unverzagt C, Rose-John S, Tholey A, Garbers C (2017); PLoS Biol., 15(1):e2000080. doi: 10.1371/journal.pbio.2000080

A Conserved cis-Regulatory Module Determines Germline Fate through Activation of the Transcription Factor DUO1 Promoter.

Peters B, Casey J, Aidley J, Zohrab S, Borg M, Twell D, Brownfield L (2017); Plant Physiol., 173(1):280-293. doi: 10.1104/pp.16.01192


Differential quantitative proteome analysis of Escherichia coli grown on acetate versus glucose.

Treitz C, Enjalbert B, Portais J C, Letisse F, Tholey A (2016); Proteomics., 16(21):2742-2746. doi: 10.1002/pmic.201600303

Genotypic and virulence characteristics of Listeria Monocytogenes recovered from food items in Lebanon.

Haidar-Ahmad N, Kissoyan K A, Fadlallah S M, El-Hajj R, Saleh M, Ghosn N, Matar G M (2016); J Infect Dev Ctries, 10(7):712-717. doi: 10.3855/jidc.7092

Combination of bottom up 2D-LC-MS and semi-top-down GelFree-LC-MS enhances coverage of proteome and low molecular weight short open reading frame encoded peptides of the archaeon Methanosarcina mazei.

Cassidy L , Prasse D, Linke D, Schmitz R A, Tholey A (2016); J Proteome Res. doi:10.1021/acs.jproteome.6b00569

ABSSeq: a new RNA-Seq analysis method based on modelling absolute expression differences.

Yang W, Rosenstiel P C, Schulenburg H (2016); BMC Genomics., 17:541. doi: 10.1186/s12864-016-2848-2

Host-parasite coevolution-rapid reciprocal adaptation and its genetic basis.

Kurtz J, Schulenburg H, Reusch T B (2016); Zoology (Jena), 119(4):241-3. doi: 10.1016/j.zool.2016.06.011

Comparative proteome analysis in Schizosaccharomyces pombeidentifies metabolic targets to improve protein production and secretion

Hung C W, Klein T, Cassidy L, Linke D, Lange S, Anders U, Bureik M, Heinzle E, Schneider K, Tholey A (2016); MCP.  doi: 10.1074/mcp.M115.051474

High Throughput Method for Analysis of Repeat Number for 28 Phase Variable Loci of Campylobacter jejuni Strain NCTC11168.

Lango-Scholey L, Aidley J, Woodacre A, Jones M A, Bayliss C D (2016); PLoS One., 11(7):e0159634. doi: 10.1371/journal.pone.0159634

The inhibition of Pseudomonas aeruginosa biofilm formation by micafungin and the enhancement of antimicrobial agent effectiveness in BALB/c mice.

Kissoyan K A, Bazzi W, Hadi U, Matar G M (2016); Biofouling, 32(7):779-86. doi: 10.1080/08927014.2016.1199021

Prevalence of carbapenem resistance encoding genes and corresponding MIC90 in enterobacteriaceae at a tertiary care center in Lebanon.

Kissoyan K A, Araj G F, Matar G M (2016); IAJAA, 6(1):5. doi: 10.3823/785

Phase variation of a Type IIG restriction-modification enzyme alters site-specific methylation patterns and gene expression in Campylobacter jejuni strain NCTC11168.

Anjum A, Brathwaite K J, Aidley J, Connerton P L, Cummings N J, Parkhill J, Connerton I, Bayliss C D (2016); Nucleic Acids Res., 44(10):4581-94. doi: 10.1093/nar/gkw019

GATA transcription factor as a likely key regulator of the Caenorhabditis elegans innate immune response against gut pathogens.

Yang W, Dierking K, Rosenstiel P C, Schulenburg H (2016); Zoology, doi: 10.1016/j.zool.2016.05.013

Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung.

Jansen G, Mahrt N, Tueffers L, Barbosa C, Harjes M, Adolph G, Friedrichs A, Krenz-Weinreich A, Rosenstiel P, Schulenburg H (2016); Evol Med Publ Health, doi: 10.1093/emph/eow016

Phosphatidylserine exposure is required for ADAM17 sheddase function.

Sommer A, Kordowski F, Büch J, Maretzki T, Evers A, Andrä J, Düsterhoft S, Michalek M, Lorenzen I, Somasundaram P, Tholey A, Sönnichsen F D, Kunzelmann K, Nehls C, Heinbockel L, Gutsmann T, Grötzinger J, Bakhdi S, Reiss K (2016); Nat Commun, 7:11523. doi: 10.1038/NCOMMS11523

Antimicrobial effectors in the nematode C. elegans – an outgroup to the Arthropoda.

Dierking K, Yang W, Schulenburg H (2016); Phil Trans R Soc Lond B., 371. doi:

The native microbiome of the nematode Caenorhabditis elegans: Gateway to a new host-microbiome model.

Dirksen P, Marsh SA, Braker I, Heitland N, Wagner S, Nakad R, Mader S, Petersen C, Kowallik V, Rosenstiel P C, Felix M A, Schulenburg H (2016); BMC Biology, 14:38. doi:10.1186/s12915-016-0258-1

Killing of Trypanozoon parasites by the equine cathelicidin eCATH.

Cauchard S, Van Reet N, Büscher P, Goux D, Grötzinger J, Leippe M, Cattoir V, Laugier C, Cauchard J (2016); Antimicrob. Agents Chemother., 60:2610-2619. doi: 10.1128/AAC.01127-15 

ß-Lactoglobulin as nanotransporter – part II: characterization of the covalent protein modification by allicin and diallyl disulfide.

Wilde S C, Treitz C, Keppler J K, Koudelka T, Kalpani K, Tholey A, Rawel H M, Schwarz K (2016); Food Chem, 197:1022-1029. doi: 10.1016/j.foodchem.2015.11.011

Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1.

Nakad R, Snoek L B, Yang W, Ellendt S, Schneider F, Mohr T G, Rösingh L, Masche A C, Rosenstiel P C, Dierking K, Kammenga J E, Schulenburg H (2016); BMC Genomics, 17: 280. doi: 10.1186/s12864-016-2603-8

Experimental evolution in silico: a custom-designed mathematical model for virulence evolution of Bacillus thuringiensis.

Strauß J F, Crain P, Schulenburg H, Telschow A (2016); Zoology, doi: 10.1016/j.zool.2016.03.005

WormExp: a web-based application for a Caenorhabditis elegans-specific gene expression enrichment analysis.

Yang W, Dierking K, Schulenburg H (2016); Bioinformatics, 32(6):943-945. doi: 10.1093/bioinformatics/btv667.

High innate immune specificity through diversification of C type lectin-like domain proteins in invertebrates.

Pees B, Yang W, Zarate-Potes A, Schulenburg H, Dierking K (2016); J. Innate Immunity, 8:129-142. doi: 10.1159/000441475

Enhancing metaproteomics – the value of models and defined microbial systems.

Herbst F A, Lünsmann V, Kjeldal H, Jehmlich N, Tholey A, von Bergen M, Lund Nielsen J, Hettich R L, Seifert J, Nielsen P H (2016); Proteomics, 16:783-798. doi: 10.1002/pmic.201500305

C-terminal charge-reversal modification and parallel use of multiple proteases facilitates identification of protein C-termini by C-terminomics.

Somasundaram P, Koudelka T, Linke D, Tholey A (2016); Proteome Res, 15:1369-1378. doi: 10.1021/acs.jproteome.6b00146

Characterization of post-translational modifications in full-length human BMP-1 confirms the presence of a rare vicinal disulfide linkage in the catalytic domain and highlights novel features of the EGF domain.

Hung C W, Koudelka T, Anastasi C, Becker A, Moali C, Tholey A (2016); Proteomics, 138:136-145. doi: 10.1016/j.jprot.2016.02.031

From top-down to bottom-up: Time-dependent monitoring of proteolytic protein degradation by LC-MS.

Tucher J, Koudelka T, Schlenk J, Tholey A (2016);J Chrom B, 1015-1016:111-120. doi: 10.1016/j.jchromb.2016.02.021

Host-parasite coevolution: Why changing population size matters.

Papkou A, Gokhale C, Traulsen A, Schulenburg H (2016); Zoology, doi: 10.1016/j.zool.2016.02.001

High instability of a nematicidal Cry toxin plasmid in Bacillus thuringiensis.

Sheppard A E, Nakad R, Saebelfeld M, Masche A C, Dierking K, Schulenburg H (2016); J.Invert.Path., 133:34-40. doi: 10.1016/j.jip.2015.11.009

High Innate Immune Specificity through Diversified C-Type Lectin-Like Domain Proteins in Invertebrates.

Pees B, Yang W, Zárate-Potes A, Schulenburg H, Dierking K (2016); J Innate Immun., 8(2):129-42. doi: 10.1159/000441475


Host-parasite coevolution in populations of constant and variable size.

Song Y, Gokhale C S, Papkou A, Schulenburg H, Traulsen A (2015); BMC Evol Biol., 15:212. doi: 10.1186/s12862-015-0462-6

Assessment of combination therapy in BALB/c mice injected with carbapenem-resistant enterobacteriaceae strains.

Salloum N A, Kissoyan K A, Fadlallah S, Cheaito K, Araj G F, Wakim R, Kanj S, Kanafani Z, Dbaibo G, Matar G M (2015); Front Microbiol., 6:999. doi: 10.3389/fmicb.2015.00999

Molecular characterization of Staphylococcal Cassette chromosome Mec and virulence encoding genes in methicillin-resistant Staphylococci at a medical center in Lebanon.

Rajeh M, Sabra A, Kissoyan K A, Fadlallah S M, Matar G M (2015); IAJAA, 5(1):3. doi: 10.3823/765

Prevalence of Clostridium Difficile toxinotypes in infected patients at a tertiary care center in Lebanon.

Moukhaiber R, Araj G F, Kissoyan K A, Cheaito K A, Matar G M (2015); J Infect Dev Ctries, 9(7):732-735. doi: 10.3855/jidc.6585

Evolutionary Transition from Pathogenicity to Commensalism: Global Regulator Mutations Mediate Fitness Gains through Virulence Attenuation.

Jansen G, Crummenerl LL, Gilbert F, Mohr T, Pfefferkorn R, Thänert R, Rosenstiel P, Schulenburg H (2015); Mol Biol Evol., 32(11) 2883-2896. doi: 10.1093/molbev/msv160

Ten years of life in compost: temporal and spatial variation of North German Caenorhabditis elegans populations.

Petersen C, Saebelfeld M, Barbosa C, Pees B, Hermann R J, Schalkowski R, Strathmann E A, Dirksen P, Schulenburg H (2015); Ecol Evol., 5(16):3250-63. doi: 10.1002/ece3.1605

Travelling at a slug’s pace: possible invertebrate vectors of Caenorhabditis nematodes.

Petersen C, Hermann R J, Barg M C, Schalkowski R, Dirksen P, Barbosa C, Schulenburg H (2015); BMC Ecol, 15:19. doi: 10.1186/s12898-015-0050-z

Superdiffusion dominates intracellular particle motion in the supercrowded cytoplasm of pathogenic Acanthamoeba castellanii.

Reverey J F, Jeon J H, Bao H, Leippe M, Metzler R, Selhuber-Unkel C (2015); Sci Rep., 5:11690. doi: 10.1038/srep11690

Host-pathogen coevolution: the selective
advantage of Bacillus thuringiensis virulence and its Cry toxin genes.

Masri L, Branca A, Sheppard AE, Papkou A, Laehnemann D, Guenther PS, Prahl S, Saebelfeld M,
Hollensteiner J, Liesegang H, Brzuszkiewicz E, Daniel R, Michiels NK, Schulte RD, Kurtz J, Rosenstiel
 P, Telschow A, Bornberg-Bauer E, Schulenburg H (2015); PLoS Biol., doi: 10.1371/journal.pbio.1002169

Using a sequential regimen to eliminate bacteria at sub-lethal antibiotic dosages.

Fuentes-Hernandez A, Plucain J, Gori F, Reding C, Peña-Miller R, Jansen G, Schulenburg H, 
Beardmore R (2015); PLoS Biol., 13(4):e1002104. doi: 10.1371/journal.pbio.1002104

Mechanistic insights into the lipid interaction of an ancient saposin-like protein.

Michalek M, Leippe M (2015); Biochemistry., 54(9):1778-86. doi: 10.1021/acs.biochem.5b00094

Why we need more ecology for genetic models like C.

Petersen C, Dirksen P, Schulenburg H (2015); Trends Genet., 31:120-127. doi: 10.1016/j.tig.2014.12.001

Overlapping and unique signatures in the proteomic and transcriptomic responses of the nematode Caenorhabditis elegans towards pathogenic Bacillus thuringiensis.

Yang W, Dierking K, Esser D, Tholey A, Leippe M, Rosenstiel P, Schulenburg H (2015); Dev Comp Immunol, 51:1-9. doi: 10.1016/j.dci.2015.02.010

Quantitative proteome analysis of Caenorhabditis elegans upon exposure to nematicidal Bacillus thuringiensis

Treitz C, Cassidy L, Höckendorf A, Leippe M, Tholey A (2015); J Proteomics, 113:337-350. doi:10.1016/j.jprot.2014.09.027

Studying Protistan Communities in Hydrocarbon-Contaminated Environments.

Johnke J, Chatzinotas A (2015); Hydrocarbon and Lipid Microbiology Protocols, 1-28. doi: 10.1007/8623_2015_169


In vitro adhesion of Acanthamoeba castellanii to soft contact lenses depends on water content and disinfection procedure.

Reverey J F, Fromme R, Leippe M, Selhuber-Unkel C (2014); Cont Lens Anterior Eye., 37(4):262-6. doi: 10.1016/j.clae.2013.11.010

Model organism proteomics as a tool for the study of host-microbiome interactions

Cassidy L, Tholey A (2014); Proteomics Clin Appl., 8(9-10):665-676. doi: 10.1002/prca.201300083

Phase variation mediates reductions in expression of surface proteins during persistent meningococcal carriage.

Alamro M, Bidmos F A, Chan H, Oldfield N J, Newton E, Bai X, Aidley J, Care R, Mattick C, Turner D P, Neal K R, Ala’aldeen D A, Feavers I, Borrow R, Bayliss C D (2014); Infect Immun., 82(6):2472-84. doi: 10.1128/IAI.01521-14

Multiple micro-predators controlling bacterial communities in the environment.

Johnke J, Cohen Y, de Leeuw M, Kushmaro A, Jurkevitch E, Chatzinotas A (2014); Curr Opin Biotechnol., 27:185-90. doi: 10.1016/j.copbio.2014.02.003

Determination of disulfide
linkages in antimicrobial peptides of the macin family by combination of top-down and bottom-up proteomics.

Hung C W, Jung S, Grötzinger J, Gelhaus C, Leippe M, Tholey A (2014); J Proteomics, 103:216-226. doi: 10.1016/j.jprot.2014.04.001

Pore-forming toxins from pathogenic amoebae.

Leippe M (2014); Appl Microbiol Biotechnol., 98(10):4347-53. doi: 10.1007/s00253-014-5673-z

Characterization and function of the first antibiotic isolated from a vent organism: the extremophile
metazoan Alvinella pompejana.

Tasiemski A, Jung S, Boidin-Wichlacz C, Jollivet D, Cuvillier-Hot V, Pradillon F, Vetriani C, Hecht 
O, Sönnichsen F D, Gelhaus C, Hung C W, Tholey A, Leippe M, Grötzinger J, Gaill F (2014)
; PLoS ONE, 9(4):e95737. doi: 10.1371/journal.pone.0095737

LC-MS based cleavage site profiling of the proteases ADAM10 and ADAM17 using proteome-derived peptide libraries

Tucher J, Linke D, Koudelka T, Cassidy L, Tredup C, Wichert R, Pietrzik C, Becker-Pauly C, Tholey A. (2014); J Proteome Res., 13(4):2205-2214. doi: 10.1021/pr401135u

The prevalence of Caenorhabditis 
elegans across 1.5 years in selected North German locations: the importance of substrate
type, abiotic parameters and Caenorhabditis competitors.

Petersen C, Dirksen P, Prahl S, Strathmann E A, Schulenburg H (2014); BMC Ecol., 14:4. doi: 10.1186/1472-6785-14-4

Effect of rifampicin and gentamicin on Shiga toxin 2 expression level and the SOS response in Escherichia Coli O104:H4.

Fadlallah S M, Rahal E A, Sabra A, Kissoyan K A, Matar G M (2014); Foodborne Pathog Dis., 12(1):47-55. doi: 10.1089/fpd.2014.1824

Repetitive DNA: A Major Source of Genetic Diversity in Campylobacter Populations?

Aidley J, Bayliss C D (2014); Campylobacter: Ecology and Evolution, ed. Sheppard, S. K., Caister Academic Press. ISBN: 978 1908230 362


Lotka-Volterra dynamics kills the Red
Queen: population size fluctuations and associated stochasticity dramatically change host-parasite

Gokhale C, Papkou A, Traulsen A, Schulenburg H (2013); BMC Evolutionary Biology, 13:254. doi: 10.1186/1471-2148-13-254

Metalloproteases meprin α
and meprin β are C- and N-procollagen proteinases important for collagen assembly and tensile

Broder C, Vadon-Le Goff S, Arnold P, Konerding M, Bahr K, Fisher L W, Müller S, Overall C M, Bond 
J S, Koudelka T, Tholey A, Hulmes D J S, Moali C, Becker-Pauly C (2013); Proc Natl Acad Sci USA, 110:14219-14224. doi: 10.1073/pnas.1305464110

Monitoring of protease catalyzed reactions
by quantitative MALDI MS using metal labeling.

Gregorius B, Jakoby T, Schaumlöffel D, Tholey A (2013); Anal Chem, 85:5184-5190. doi: 10.1021/ac4005452

membrane-proximal domain of ADAM17 represents the putative molecular switch of its shedding activity
operated by protein-disulfide isomerase.

Düsterhöft S, Jung S, Hung C W, Tholey A, Sönnichsen F D, Grötzinger J, Lorenzen I (2013); J Am Chem Soc, 135:5776-5781. doi: 10.1021/ja400340u

Gene-environment and protein degradation
signatures characterize genomic and phenotypic diversity in wild Caenorhabditis elegans populations.

Volkers R M, Snoek L B, Van Hellenberg Hubar C J V, Coopman R, Chen W, Yang W, Sterken M G, 
Schulenburg H, Braeckman B P, Kammenga J E (2013); 
BMC Biol., 13:254. doi: 10.1186/1741-7007-11-93

Sex differences in host defense interfere with parasite-mediated selection for outcrossing
during host-parasite coevolution.

Masri L, Schulte R, Timmermeyer N, Thanisch S, Crummenerl L, Jansen G, Michiels N K, Schulenburg 
H (2013);. Ecol. Lett., 16:461-466. doi: 10.1111/ele.12068

When the most potent combinations of antibiotics select for the greatest bacterial
load: the smile-frown transition.

Peña-Miller R, Laehnemann D, Jansen G, Fuentes-Hernandez A, Rosenstiel P, Schulenburg H,
 Beardmore R (2013); PLoS Biol., 11:e1001540. doi: 10.1371/journal.pbio.1001540

Anti-Aspergillus Fumigatus IgY antibodies and their protective efficacy in cyclosporine A treated BALB/C mice.

Kissoyan K A, Al-Akl N S, Abdelnoor A M (2013); IOSR Journal of Pharmacy, 3(7):23-29. ISSN: 2319-4219

Optimized fragmentation conditions for iTRAQ-labeled phosphopeptides

Linke D, Hung C W, Cassidy L, Tholey A (2013); J Proteome Res., 12(6):2755-63. doi: 10.1021/pr400113n

EGFR signaling in the brain is necessary for olfactory learning in Drosophila larvae.

Rahn T, Leippe M, Roeder T, Fedders H (2013); Learn Mem., 20(4):194-200. doi: 10.1101/lm.029934.112

The Janthinobacterium sp. HH01 genome encodes a homologue of the V. cholerae CqsA and L. pneumophila LqsA autoinducer synthases.

Hornung C, Poehlein A, Haack F S, Schmidt M, Dierking K, Pohlen A, Schulenburg H, Blokesch M, Plener L, Jung K, Bonge A, Krohn-Molt I, Utpatel C, Timmermann G, Spieck E, Pommerening-Röser A, Bode E, Bode H B, Daniel R, Schmeisser C, Streit W R (2013); PLoS One, 8(2). doi: 10.1371/journal.pone.0055045

Structure and function of a unique pore-forming protein
from a pathogenic acanthamoeba.

Michalek M, Sönnichsen F D, Wechselberger R, Dingley A J, Hung C-W, Kopp A, Wienk H,
Simanski M, Herbst R, Lorenzen I, Marciano-Cabral F, Gelhaus C, Gutsmann T, Tholey 
A, Grötzinger J, Leippe M (2013); Nature Chem Biol, 9(1):37-42. doi: 10.1038/nchembio.1116


Tandem mass tag protein labeling for top-down identification and quantification.

Hung C W, Tholey A (2012); 
Anal Chem, 84:161-170. doi: 10.1021/ac202243r

Quantitative protease cleavage site profiling using
tandem mass tag labeling and LC-MALDI-TOF/TOF MS/MS analysis.

Jakoby T, van den Berg B H J, Tholey A (2012); J Proteome Res, 11:1812-
1820. doi: 10.1021/pr201051e

The saposin-like protein SPP-12 is an antimicrobial polypeptide
in pharyngeal neurons of Caenorhabditis elegans and participates in defence against a natural
bacterial pathogen.

Höckendorf A, Stanisak M, Leippe M (2012); Biochem J, 445:205-212. doi: 10.1042/BJ20112102

Isolation of erythrocytes infected with viable early stages of Plasmodium falciparum by flow cytometry.

Philipp S, Oberg HH, Janssen O, Leippe M, Gelhaus C (2012); Cytometry A., 81(12):1048-54. doi: 10.1002/cyto.a.22226

The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2

Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, Giaisi M, Köhler R, Müller WW, Proksch P, Leippe M, Janssen O, Désaubry L, Krammer PH, Li-Weber M (2012); Chem Biol., 19(9):1093-104. doi: 10.1016/j.chembiol.2012.07.012

SPP-3, a saposin-like protein of Caenorhabditis elegans, displays antimicrobial and pore-forming activity and is located in the intestine and in one head neuron.

Hoeckendorf A, Leippe M (2012); Dev Comp Immunol., 38(1):181-6. doi: 10.1016/j.dci.2012.05.007

Macin family of antimicrobial proteins combines antimicrobial and nerve repair activities.

Jung S, Sönnichsen F D, Hung C W, Tholey A, Boidin-Wichlacz C, Haeusgen W, Gelhaus C, Desel C, Podschun R, Waetzig V, Tasiemski A, Leippe M, Grötzinger J (2012); J Biol Chem., 287(17):14246-58. doi: 10.1074/jbc.M111.336495

Cationic detergents enable the separation of membrane proteins of Plasmodium falciparum-infected erythrocytes by 2D gel electrophoresis.

Philipp S, Jakoby T, Tholey A, Janssen O, Leippe M, Gelhaus C (2012); Electrophoresis., 33(7):1120-8. doi: 10.1002/elps.201100520


Proteomic Techniques for Plant-Fungal Interactions

Vincent D, Tan K C, Cassidy L, Solomon P S, Oliver R P (2011); Methods Mol Biol., 835:75-96. doi: 10.1007/978-1-61779-501-5_5

A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas aeruginosa biofilm formation and virulence in Caenorhabditis elegans.

Bijtenhoorn P, Mayerhofer H, Muller-Dieckmann J, Utpatel C, Schipper C, Hornung C, Szesny M, Grond S, Thruner A, Brzuszkiewicz E, Daniel R, Dierking K, Schulenburg H, Streit W R (2011); PLoS One, 6(10):e26278. doi: 10.1371/journal.pone.0026278.

Localization of antimicrobial peptides in the tunic of Ciona intestinalis (Ascidiacea, Tunicata) and their involvement in local inflammatory-like reactions.

Di Bella M A, Fedders H, De Leo G, Leippe M (2011); Results Immunol., 1(1):70-5. doi: 10.1016/j.rinim.2011.09.001

Host-parasite local adaptation
after experimental coevolution of Caenorhabditis elegans and its microparasite Bacillus thuringiensis.

Schulte R D, Makus C, Hasert B, Michiels N K, Schulenburg H (2011); 
Proc. R. Soc. Lond. B, 278(1719):2832-2839. doi: 10.1098/rspb.2011.0019

Unusual Regulation of a STAT Protein by a SLC6 Family Transporter in Caenorhabditis elegans Epidermal Innate Immunity.

Dierking K, Polanowska J, Omi S, Engelmann I, Gut M, Lembo F, Ewbank J J, Pujol N (2011); Cell Host Microbe, 9(5):425-435. doi: 10.1016/j.chom.2011.04.011

Human beta-defensin 2 and beta-defensin 3 chimeric peptides reveal the structural basis of the pathogen specificity of their parent molecules.

Jung S, Mysliwy J, Spudy B, Lorenzen I, Reiss K, Gelhaus C, Podschun R, Leippe M, Grötzinger J (2010); Antimicrob Agents Chemother., 55(3):954-60. doi: 10.1128/AAC.00872-10


Allicin and derivates are cysteine protease inhibitors with antiparasitic activity.

Waag T, Gelhaus C, Rath J, Stich A, Leippe M, Schirmeister T (2010); Bioorg Med Chem Lett., 20(18):5541-3. doi: 10.1016/j.bmcl.2010.07.062

Multiple reciprocal adaptations
and rapid genetic change upon experimental coevolution of an animal host and its microbial parasite.

Schulte R D, Makus C, Hasert B, Michiels N K, Schulenburg H (2010); 
Proc. Natl. Acad. Sci. USA, 107(16):7359–7364. doi: 10.1073/pnas.1003113107

The adapter protein Nck: role of individual SH3 and SH2 binding modules for protein interactions in T lymphocytes.

Lettau M, Pieper J, Gerneth A, Lengl-Janssen B, Voss M, Linkermann A, Schmidt H, Gelhaus C, Leippe M, Kabelitz D, Janssen O (2010); Protein Sci., 19(4):658-69. doi: 10.1002/pro.334

Caenopore-5: the three-dimensional structure of an antimicrobial protein from Caenorhabditis elegans.

Mysliwy J, Dingley A J, Stanisak M, Jung S, Lorenzen I, Roeder T, Leippe M, Grötzinger J (2010); Dev Comp Immunol., 34(3):323-30. doi: 10.1016/j.dci.2009.11.003

Caenopores are antimicrobial
peptides in the nematode Caenorhabditis elegans instrumental in nutrition and immunity.

Roeder T, Stanisak M, Gelhaus C, Bruchhaus I, Grötzinger J, Leippe M (2010); 
Dev Comp Immunol, 34 (2):203-209. doi: 10.1016/j.dci.2009.09.010


On-bead screening of a combinatorial fumaric acid derived peptide library yields antiplasmodial cysteine protease inhibitors with unusual peptide sequences.

Machon U, Büchold C, Stempka M, Schirmeister T, Gelhaus C, Leippe M, Gut J, Rosenthal P J, Kisker C, Leyh M, Schmuck C (2009); J Med Chem., 52(18):5662-72. doi: 10.1021/jm900629w

Novel 2H-isoquinolin-3-ones as antiplasmodial falcipain-2 inhibitors.

Micale N, Ettari R, Schirmeister T, Evers A, Gelhaus C, Leippe M, Zappalà M, Grasso S (2009);
Bioorg Med Chem., 17(18):6505-11. doi: 10.1016/j.bmc.2009.08.013

Enrichment and analysis of secretory lysosomes from lymphocyte populations.

Schmidt H, Gelhaus C, Lucius R, Nebendahl M, Leippe M, Janssen O (2009); BMC Immunol., 10:41. doi: 10.1186/1471-2172-10-41

Antimicrobial properties of the equine alpha-defensin DEFA1 against bacterial horse pathogens.

Bruhn O, Cauchard J, Schlusselhuber M, Gelhaus C, Podschun R, Thaller G, Laugier C, Leippe M, Grötzinger J (2009); Vet Immunol Immunopathol., 130(1-2):102-6. doi: 10.1016/j.vetimm.2009.01.005

2-D DIGE analysis of the proteome of extracts from peanut variants reveals striking differences in major allergen contents.

Schmidt H, Gelhaus C, Latendorf T, Nebendahl M, Petersen A, Krause S, Leippe M, Becker W M, Janssen O (2009); Proteomics., 9(13):3507-21. doi: 10.1002/pmic.200800938

The human antimicrobial protein psoriasin acts by permeabilization of bacterial membranes.

Michalek M, Gelhaus C, Hecht O, Podschun R, Schröder J M, Leippe M, Grötzinger J (2009);
Dev Comp Immunol. 2009, 33(6):740-6. doi: 10.1016/j.dci.2008.12.005

Antimicrobial activity of bovine psoriasin.

Regenhard P, Leippe M, Schubert S, Podschun R, Kalm E, Grötzinger J, Looft C (2009); Vet Microbiol., 136(3-4):335-40. doi: 10.1016/j.vetmic.2008.12.001

Major cysteine peptidases of Entamoeba histolytica are required for aggregation and digestion of erythrocytes but are dispensable for phagocytosis and cytopathogenicity.

Irmer H, Tillack M, Biller L, Handal G, Leippe M, Roeder T, Tannich E, Bruchhaus I (2009); Mol Microbiol., 72(3):658-67. doi: 10.1111/j.1365-2958.2009.06672.x

Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.

Ziegler K, Kurz CL, Cypowyj S, Couillault C, Pophillat M, Pujol N, Ewbank J J (2009); Cell Host Microbe, 5(4):341-352. doi: 10.1016/j.chom.2009.03.006

Significance of the cyclic structure and of arginine residues for the antibacterial activity of arenicin-1 and its interaction with phospholipid and lipopolysaccharide model membranes.

Andrä J, Hammer M U, Grötzinger J, Jakovkin I, Lindner B, Vollmer E, Fedders H, Leippe M, Gutsmann T (2009); Biol Chem., 390(4):337-49. doi: 10.1515/BC.2009.039

Uncovering the evolutionary history of innate immunity: the simple metazoan Hydra uses epithelial cells for host defence.

Bosch T C, Augustin R, Anton-Erxleben F, Fraune S, Hemmrich G, Zill H, Rosenstiel P, Jacobs G, Schreiber S, Leippe M, Stanisak M, Grötzinger J, Jung S, Podschun R, Bartels J, Harder J, Schröder J M (2009); Dev Comp Immunol., 33(4):559-69. doi: 10.1016/j.dci.2008.10.004


Synthesis and evaluation of non-peptidic cysteine protease inhibitors of P. falciparum derived from etacrynic acid.

Dude M A, Kaeppler U, Herb M, Schiller M, Schulz F, Vedder B, Heppner S, Pradel G, Gut J, Rosenthal P J, Schirmeister T, Leippe M, Gelhaus C (2008); Molecules., 14(1):19-35. doi: 10.3390/molecules14010019

An efficient fluorimetric method to measure the viability of intraerythrocytic Plasmodium falciparum.

Evers A, Heppner S, Leippe M, Gelhaus C (2008); Biol Chem., 389(12):1523-5. doi: 10.1515/BC.2008.167

An exceptional salt-tolerant antimicrobial
peptide derived from a novel gene family of hemocytes of the marine invertebrate Ciona intestinalis.

Fedders H, Michalek M, Grötzinger J, Leippe M (2008); 
Biochem. J, 416 (1): 65-75. doi: 10.1042/BJ20080398

Membrane pore formation by pentraxin proteins from Limulus, the American horseshoe crab.

Harrington J M, Chou H T, Gutsmann T, Gelhaus C, Stahlberg H, Leippe M, Armstrong P B (2008);
Biochem J., 413(2):305-13. doi: 10.1042/BJ20071357

2-D DIGE analyses of enriched secretory lysosomes reveal heterogeneous profiles of functionally relevant proteins in leukemic and activated human NK cells.

Schmidt H, Gelhaus C, Nebendahl M, Lettau M, Watzl C, Kabelitz D, Leippe M, Janssen O (2008); Proteomics., 8(14):2911-25. doi: 10.1002/pmic.200800170

The antimicrobial peptide NK-2, the core region of mammalian NK-lysin, kills intraerythrocytic Plasmodium falciparum.

Gelhaus C, Jacobs T, Andrä J, Leippe M (2008); Antimicrob Agents Chemother., 52(5):1713-20. doi: 10.1128/AAC.01342-07

Distinct innate immune responses to infection and wounding in the C. elegans epidermis.

Pujol N, Cypowyj S, Ziegler K, Millet A, Astrain A, Goncharov A, Jin Y, Chisholm A D, Ewbank J J (2008); Curr. Biol., 18(7):481-489. doi: 10.1016/j.cub.2008.02.079

Structure and mode of action of the antimicrobial peptide arenicin.

Andrä J, Jakovkin I, Grötzinger J, Hecht O, Krasnosdembskaya AD, Goldmann T, Gutsmann T, 
Leippe M (2008); Biochem J., 410 (1): 
113-122. doi: 10.1042/BJ20071051

Specificity of the innate immune system and diversity of C-type lectin domain (CTLD) proteins in the nematode Caenorhabditis elegans.

Schulenburg H, Hoeppner M P, Weiner J 3rd, Bornberg-Bauer E (2008); Immunobiology., 213(3-4):237-50. doi: 10.1016/j.imbio.2007.12.004

A reverse search for antimicrobial peptides in Ciona intestinalis: identification of a gene family expressed in hemocytes and evaluation of activity.

Fedders H1, Leippe M (2008); Dev Comp Immunol., 32(3):286-98. doi: 10.1016/j.dci.2007.06.003


Synthesis and pharmacological evaluation of fluorescent and photoactivatable analogues of antiplasmodial naphthylisoquinolines.

Bringmann G, Gampe CM, Reichert Y, Bruhn T, Faber J H, Mikyna M, Reichert M, Leippe M, Brun R, Gelhaus C (2007); J Med Chem., 50(24):6104-15. doi: 10.1021/jm061464w

A novel horse alpha-defensin: gene transcription, recombinant expression and characterization of the structure and function.

Bruhn O, Regenhard P, Michalek M, Paul S, Gelhaus C, Jung S, Thaller G, Podschun R, Leippe M, Grötzinger J, Kalm E (2007); Biochem J., 407(2):267-76. doi: 10.1042/BJ20070747

Screening of protease inhibitors as antiplasmodial agents. Part I: Aziridines and epoxides.

Schulz F, Gelhaus C, Degel B, Vicik R, Heppner S, Breuning A, Leippe M, Gut J, Rosenthal P J, Schirmeister T (2007); ChemMedChem., 2(8):1214-24. doi: 10.1002/cmdc.200700070


Aziridide-based inhibitors of cathepsin L: synthesis, inhibition activity, and docking studies.

Vicik R, Busemann M, Gelhaus C, Stiefl N, Scheiber J, Schmitz W, Schulz F, Mladenovic M, Engels B, Leippe M, Baumann K, Schirmeister T (2006); ChemMedChem., 1(10):1126-41. doi: 10.1002/cmdc.200600106

A novel saposin-like protein of Entamoeba histolytica with membrane-fusogenic activity.

Winkelmann J, Leippe M, Bruhn H (2006); Mol Biochem Parasitol., 147(1):85-94. doi: 10.1016/j.molbiopara.2006.01.010

JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets.

Verma S, Ziegler K, Ananthula P, Co J K G, Frisque R J, Yanagihara R, Nerurkar V R (2006); Virology, 345:457-467. doi: 10.1016/j.virol.2005.10.012

Dissection of the mechanisms of cytolytic and antibacterial activity of lysenin, a defence protein of the annelid Eisenia fetida.

Bruhn H, Winkelmann J, Andersen C, Andrä J, Leippe M (2006); Dev Comp Immunol., 30(7):597-606. doi: 10.1016/j.dci.2005.09.002


Fractionation and identification of proteins by 2-DE and MS: towards a proteomic analysis of Plasmodium falciparum.

Gelhaus C, Fritsch J, Krause E, Leippe M (2005); Proteomics., 5(16):4213-22. doi: 10.1002/pmic.200401285

Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells.

Gelhaus C, Vicik R, Schirmeister T, Leippe M (2005); Biol Chem., 386(5):499-502. doi: 10.1515/BC.2005.059

A Dictyostelium mutant
with reduced lysozyme levels compensates by increased phagocytic activity.

Müller I, Subert N, Otto H, Herbst R, Rühling H, Maniak M, Leippe M (2005); J. Biol. Chem., 280:
10435-10443. doi: 10.1074/jbc.M411445200

The genome of the protist parasite Entamoeba histolytica.

Loftus B, Anderson I, Davies R, Alsmark UC, Samuelson J, Amedeo P, Roncaglia P, Berriman M, Hirt
 RP, Mann BJ, Nozaki T, Suh B, Pop M, Duchene M, Ackers J, Tannich E, Leippe M, Hofer M, Bruchhaus 
I, Willhoeft U, Bhattacharya A, Chillingworth T, Churcher C, Hance Z, Harris B, Harris D, Jagels 
K, Moule S, Mungall K, Ormond D, Squares R, Whitehead S, Quail MA, Rabbinowitsch E, Norbertczak
 H, Price C, Wang Z, Guillen N, Gilchrist C, Stroup SE, Bhattacharya S, Lohia A, Foster PG, Sicheritz-
Ponten T, Weber C, Singh U, Mukherjee C, El-Sayed NM, Petri WA Jr, Clark CG, Embley TM, Barrell
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865-868. doi: 10.1038/nature03291

Ancient weapons: the three-dimensional structure of amoebapore A.

Leippe M, Bruhn H, Hecht O, Grötzinger J (2005); Trends Parasitol., 21(1):5-7. doi: 10.1016/j.pt.2004.10.009


A rapid in-vitro polyomavirus DNA replication assay.

Ziegler K, Bui T, Frisque R J, Grandinetti A, Nerurkar V R (2004); J Virol Meth, 122:123-127. doi: 10.1016/j.jviromet.2004.08.012

Antimicrobial and pore-forming peptides of free-living and potentially highly pathogenic Naegleria fowleri are released from the same precursor molecule.

Herbst R, Marciano-Cabral F, Leippe M (2004); J Biol Chem., 279(25):25955-8. doi: 10.1074/jbc.M401965200

Synthesis and antiplasmodial activity of a cysteine protease-inhibiting biotinylated aziridine-2,3-dicarboxylate.

Gelhaus C, Vicik R, Hilgenfeld R, Schmidt CL, Leippe M, Schirmeister T (2004); Biol Chem., 385(5):435-8. doi: 10.1515/BC.2004.050

Membrane lipid composition protects Entamoeba histolytica from self-destruction by its pore-forming toxins.

Andrä J1, Berninghausen O, Leippe M (2004); FEBS Lett., 564(1-2):109-15. doi: 10.1016/S0014-5793(04)00324-2

Solution structure of the pore-forming protein of Entamoeba histolytica.

Hecht O, van Nuland N, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grötzinger J
 (2004); J Biol Chem
, 279, 17834-17841. doi: 10.1074/jbc.M312978200

Ancient weapons for attack and defense: the pore-forming polypeptides of pathogenic enteric and free-living amoeboid protozoa.

Leippe M, Herbst R (2004); J Eukaryot Microbiol., 51(5):516-21.


Amoebapores, archaic effector peptides of protozoan origin, are discharged into phagosomes and kill bacteria by permeabilizing their membranes.

Andrä J1, Herbst R, Leippe M (2003); Dev Comp Immunol., 27(4):291-304. doi: 10.1016/S0145-305X(02)00106-4

NK-lysin and its shortened analog NK-2 exhibit potent activities against Trypanosoma cruzi.

Jacobs T, Bruhn H, Gaworski I, Fleischer B, Leippe M (2003); Antimicrob Agents Chemother., 47(2):607-13. PMCID: PMC151766


Membrane-permeabilizing polypeptides of amoebae – constituents of an archaic antimicrobial system.

Bruhn H, Leippe M (2001); Zoology (Jena)., 104(1):3-11. doi: 10.1078/0944-2006-00001


Evidence that hyaluronidase is not involved in tissue invasion of the protozoan parasite Entamoeba histolytica.

Nickel R, Stern R, Leippe M (2000); Infect Immun., 68(5):3053-5.

Two major ‘higher molecular mass proteinases’ of Entamoeba histolytica are identified as cysteine proteinases 1 and 2.

Hellberg A, Leippe M, Bruchhaus I (2000); Mol Biochem Parasitol., 105(2):305-9.


Candidacidal activity of shortened synthetic analogs of amoebapores and NK-lysin.

Andrä J, Leippe M (1999); Med Microbiol Immunol., 188(3):117-24. doi: 10.1007/s004300050113