GRK 1673:  Functional Molecular Infection Epidemiology

• Subject Area: Microbiology, Virology and Immunology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 164295104

• Final Report Year: 2016

Final Report Abstract

In the era of globalisation, the prevention and spread of infectious diseases continues to play a crucial role for scientists v\/orldvwde. The international research training group (IRTG) GRK 1673 „Functional Molecular Infection Epidemiology" \was a combined effort of scientific institutions in Berlin and Hyderabad (India), located at Freie Universität Berlin. In Berlin, the Freie Universität Berlin (Department of Veterinary Medicine), Humboldt Universität zu Berlin (Institute of Biology), Robert Koch Institute, Charitö - Unversitätsmedizin and the Max Planck Institute for Infection Biology were intimately involved in this network. In Hyderabad, the University of Hyderabad, Centre for Cellular and Molecular Biology (CCMB), Centre for DMA Fingerprinting and Diagnostics (CDFD), Mahavir Hospital and LEPRA - Blue Peter Research Centre were committed to the project. During the funding period, new collaborations were formed with KMC and Wenlock Hospital in Mangalore and NIRT in Chennai. Funding for the IRTG was only granted on the German side, while the grant application efforts of the Indian partners were not successful. In spite of this great financial drawback, besides many cultural challenges, the Indian scientists were extremely cooperative on all levels. Projects in Berlin benefitted from the excellent bioinformatics competences in Hyderabad. In addition, the project gave German scientists access to medical samples and patient cohorts in India. On the other hand, scientists from India profited from the infection biology expertise in Berlin. Research focused on the innovative interdisciplinary theme of Functional Molecular Infection Epidemiology. This new research area analyses the influence of genetic variations both of pathogens and human hosts on the course and distribution of infectious diseases. Such a scientific perspective allows deep insights into the link between global distribution and control of infections and genetically determined courses of disease. The studies concentrated on bacterial pathogens such as Mycobacterium tuberculosis, Mycobacterium avium. Streptococcus pneumoniae, multi resistant ESBL forming E. coli, Helicobacter pylori and Pseudomonas aeruginosa, as well as on parasitical pathogens causing Malaria and Filariasis. ' . By the end of the funding phase, 13 students graduated from the program in Berlin and more than 60 publications were published. In addition to scientific activities and courses in practical laboratory techniques, bioinformatics, infection epidemiology and soft skills; the program enabled an intensive intercultural exchange, supported by weekly webinars, three joint summer/winter schools, a significant number of workshops and more than 50 research stays. In particular. Doctoral students and Post Doctoral scientists benefitted from this intercultural scientific experience. During the five year funding period close ties were formed that will continue to be strengthened In the future, which ultimately makes the IRTG a great success in the long run.

Publications

• "Genome of Helicobacter pylori Strain 908." Journal of Bacteriology 192, no. 24 (2010): 6488-9
  Devi, S. H., T. D. Taylor, T. S. Avasthi, S. Kondo, Y. Suzuki, F. Megraud, and N. Ahmed
  
• "Genomes of Two Chronological Isolates (Helicobacter pylori 2017 and 2018) of the West African Helicobacter pylori Strain 908 Obtained from a Single Patient." Journal of Bacteriology 193, no. 13 (2011): 3385-6
  Avasthi, T. S., S. H. Devi, T. D. Taylor, N. Kumar, R. Saddam, S. Kondo, Y. Suzuki, H. Lamouliatte, F. Megraud, and N. Ahmed
  
• "Modulation of Specific and Allergy-Related Immune Responses by Helminths." Journal of Biomedicine and Biotechnology 2011, (2011): 821578
  Danilowicz-Luebert, E., N. L. O'Regan, S. Steinfelder, and S. Hartmann
  
• "Tight Association of N-Terminal and Catalytic Subunits of Rabbit 12/15-Lipoxygenase Is Important for Protein Stability and Catalytic Activity." Biochimica et Biophysics Acta 1811, no. 12 (2011): 1001-10
  Ivanov, I., A. Di Venere, T. Horn, P. Scheerer, E. Nicolai, S. Stehling, C. Richter, E. Skrzypczak-Jankun, G. Mei, M. Maccarrone, and H. Kühn
  
• "'Life-Style' Control Networks in Escherichia coli: Signaling by the Second Messenger c-di-GMP." Journal of Biotechnology 160, no. 1- 2(2012): 10-6
  Povolotsky, T. L., and R. Hengge
  (See online at https://doi.org/10.1016/j.jbiotec.2011.12.024)
• "The Helicobacter pylori Virulence Effector CagA Abrogates Human Beta-Defensin 3 Expression Via Inactivation of EGFR Signaling." Cell Host Microbe 11, no. 6 (2012): 576-86
  Bauer, B., E. Pang, C. Holland, M. Kessler, S. Bartfeld, and T. F. Meyer
  (See online at https://doi.org/10.1016/j.chom.2012.04.013)
• "An ATP2B4 Polymorphism Protects against Malaria in Pregnancy." Journal of Infectious Diseases 207, no. 10 (2013): 1600-3
  Bedu-Addo, G., S. Meese, and F. P. Mockenhaupt
  
• "Association of a Common TLR-6 Polymorphism with Coronary Artery Disease - Implications for Healthy Ageing?" Immunity and Ageing 10, no. 1 (2013): 43
  Hamann, L., A. Koch, S. Sur, N. Hoefer, C. Glaeser, S. Schulz, M. Gross, A. Franke, U. Nothlings, K. Zacharowski, and R. R. Schumann
  (See online at https://doi.org/10.1186/1742-4933-10-43)
• "Conversion of Pro-Inflammatory Murine ALOX5 into an Anti-Inflammatory 15S-Lipoxygenating Enzyme by Multiple Mutations of Sequence Determinants." Archives of Biochemistry and Biophysics 530, no. 1 (2013): 40-7
  Hofheinz, K., K. R. Kakularam, S. Adel, M. Anton, A. Polymarasetty, P. Reddanna, H. Kühn, and T. Horn
  (See online at https://doi.org/10.1016/j.abb.2012.11.015)
• "Expression of lnterleukin-6 Family Receptors in NK92 Cells Is Regulated by Cytokines and Not through Direct Interaction with Plasmodium falciparum-Infected Erythrocytes." Journal of Interferon and Cytokine Research 33, no. 2 (2013): 65-71
  Böttger, E., E. Grangeiro de Carvalho, S. Meese, J. F. Kun, and M. Esen
  
• "Functional Characterization of Genetic Enzyme Variations in Human Lipoxygenases." Redox Biology no, 1 (2013): 566-77
  Horn, T., K. Reddy Kakularam, M. Anton, C. Richter, P. Reddanna, and H. Kühn
  (See online at https://doi.org/10.1016/j.redox.2013.11.001)
• "Lipoxygenase Pathways in Homo neanderthalensis: Functional Comparison with Homo sapiens Isoforms." Journal of Lipid Research 54, no. 5 (2013): 1397-409
  Chaitidis, P., S. Adel, M. Anton, D. Heydeck, H. Kühn, and T. Horn
  (See online at https://doi.org/10.1194/jlr.M035626)
• "Molecular Basis for the Catalytic Inactivity of a Naturally Occurring near-Null Variant of Human ALOX15." Biochimica et Biophysics Acta 1831, no. 12(2013): 1702-13
  Horn, T., I. Ivanov, A. Di Venere, K. R. Kakularam, P. Reddanna, M. L. Conrad, C. Richter, P. Scheerer, and H. Kühn
  (See online at https://doi.org/10.1016/j.bbalip.2013.08.004)
• "Role of Arg403 for Thermostability and Catalytic Activity of Rabbit 12/15-Lipoxygenase." Biochimica et Biophysics Acta 1831, no. 6 (2013): 1079-88
  Di Venere, A., T. Horn, S. Stehling, G. Mei, L. Masgrau, A. Gonzalez-Lafont, H. Kühn, and I. Ivanov
  (See online at https://doi.org/10.1016/j.bbalip.2013.02.006)
• "The Crystal Structure of Lipopolysaccharide Binding Protein Reveals the Location of a Frequent Mutation That Impairs Innate Immunity." Immunity 39, no. 4 (2013): 647-60
  Eckert, J. K., Y. J. Kim, J. I. Kim, K. Gürtler, D. Y. Oh, S. Sur, L. Lundvall, L. Hamann, A. van der Ploeg, P. Pickkers, E. Giamarellos-Bourboulis, A. V. Kubarenko, A. N. Weber, M. Kabesch, O. Kumpf, H. J. An, J. O. Lee, and R. R. Schumann
  (See online at https://doi.org/10.1016/j.immuni.2013.09.005)
• "Abundance of Mycobacterium avium ssp. hominissuis in Soil and Dust in Germany - Implications for the Infection Route." Letters in Applied Microbiology 59, no. 1 (2014): 65-70
  Lahiri, A, J. Kneisel, I. Kloster, E. Kamal, and A. Lewin
  (See online at https://doi.org/10.1111/lam.12243)
• "Association of Polymorphisms in the ALOX15b Gene with Coronary Artery Disease." Clinical Biochemistry 47, no. 6 (2014): 349-55
  Wuest, S. J., T. Horn, J. Marti-Jaun, H. Kühn, and M. Hersberger
  (See online at https://doi.org/10.1016/j.clinbiochem.2013.12.013)
• "Correlation between the Genomic o454-nlpD Region Polymorphisms, Virulence Gene Equipment and Phylogenetic Group of Extraintestinal Escherichia coli (Expec) Enables Pathbtyping Irrespective of Host, Disease and Source of Isolation." Gut Pathogens 6, (2014): 37
  Ewers, C., F. Dematheis, H. D. Singamaneni, N. Nandanwar, A. Fruth, I. Diehl, T. Semmler, and L. H. Wieler
  (See online at https://doi.org/10.1186/s13099-014-0037-x)
• "Cyclic-di-GMP Signalling and Biofilm-Related Properties of the Shiga Toxin-Producing 2011 German Outbreak Escherichia coli O104:H4." EMBO Molecular Medicine 6, no. 12 (2014): 1622-37
  Richter, A. M., T. L. Povolotsky, L. H. Wieler, and R. Hengge
  (See online at https://doi.org/10.15252/emmm.201404309)
• "Filariasis Asymptomatically Infected Donors Have Lower Levels of Disialylated IgG Compared to Endemic Normals." Parasite Immunology 36, no. 12 (2014): 713-20
  O'Regan, N. L., S. Steinfelder, C. Schwedler, G. B. Rao, Aparna Srikantam, V. Blanchard, and S. Hartmann
  (See online at https://doi.org/10.1111/pim.12137)
• "Genetic Characterization of German Mycobacterium avium Strains Isolated from Different Hosts and Specimens by Multilocus Sequence Typing." International Journal of Medical Microbiology 304, no. 8 (2014): 941-8
  Kolb, J., D. Hillemann, P. Mobius, J. Reetz, A Lahiri, A. Lewin, S. Rusch-Gerdes, and E. Richter
  (See online at https://doi.org/10.1016/j.ijmm.2014.06.001)
• "Grsf1-Induced Translation of the SNARE Protein Usel Is Required for Expansion of the Erythroid Compartment." PLoS One 9, no. 9 (2014): e104631
  Nieradka, A., C. Ufer, K. Thiadens, G. Grech, R. Horos, M. van Coevorden-Hameete, E. van den Akker, S. Sofi, H. Kuhn, and M. von Lindem
  (See online at https://doi.org/10.1371/journal.pone.0104631)
• "Identification and Comparative Analysis of a Genomic Island in Mycobacterium avium subsp. hominissuis.” FEBS Letters 588, no. 21 (2014): 3906-11
  Lahiri, A., A. Sanchini, T. Semmler, H. Schäfer, and A. Lewin
  (See online at https://doi.org/10.1016/j.febslet.2014.08.037)
• "No Association of the p53 Codon 72 Polymorphism with Malaria in Ghanaian Primiparae and Rwandan Children." The American Journal of Tropical Medicine and Hygiene 90, no. 6(2014): 1133-4
  Gai, P. P., S. Meese, G. Bedu-Addo, J. B. Gahutu, and F. P. Mockenhaupt
  (See online at https://doi.org/10.4269/ajtmh.14-0050)
• "Reduced Prevalence of Placental Malaria in Primiparae with Blood Group 0." Malaria Journal 13, no. 1 (2014): 289
  Bedu-Addo, G., P. P. Gai, S. Meese, T. A. Eggelte, K. Thangaraj, and F. P. Mockenhaupt
  (See online at https://doi.org/10.1186/1475-2875-13-289)
• "Soluble CEACAM8 Interacts with CEACAM1 Inhibiting TLR2-Triggered Immune Responses." PLoS One 9, no. 4 (2014): e94106
  Singer, B. B., L. Opp, A. Heinrich, F. Schreiber, R. Binding-Liermann, L. C. Berrocal-Almanza, K. A. Heyl, M. M. Muller, A. Weimann, J. Zweigner, and H. Slevogt
  (See online at https://doi.org/10.1371/journal.pone.0094106)
• "The Course of Gastric Cancer Following Surgery Is Associated with Genetic Variations of the Interleukin-1 Receptor Antagonist and Interleukin-1 beta." Gastric Cancer18, no. 1 (2014): 77-83
  van der Ploeg, A. H., O. Kumpf, E. Seelow, L. C. Berrocal-Almanza, P. M. Schlag, R. R. Schumann, and L. Hamann
  (See online at https://doi.org/10.1007/s10120-014-0349-z)
• (2014). Host defensin (human β-defensin 3) regulation by Helicobacter pylori. (Berlin: Humoldt Universität)
  Pang, E.
  
• (2014). The genetic diversity of Mycobacterium avium subsp. hominissuis. (Berlin: Freie Universität)
  Lahiri, A.
  
• (2014). Untersuchungen zum funktionellen Einfluss von genetischen Variationen in humanen Lipoxygenasen und anderen Genen des LOX Stoffwechsel. (Berlin: Freie Universität)
  Horn, T.
  
• ”Brugia malayi Microfilariae Induce a Regulatory Monocyte/Macrophage Phenotype That Suppresses Innate and Adaptive Immune Responses." PLoS Neglected Tropical Diseases 8, no. 10 (2014): e3206
  O'Regan, N. L., S. Steinfelder, G. Venugopal, G. B. Rao, R. Lucius, A. Srikantam, and S. Hartmann
  (See online at https://doi.org/10.1371/journal.pntd.0003206)
• "A Novel Reading Scheme for Assessing the Extent of Radiographic Abnormalities and Its Association with Disease Severity in Sputum Smear-Positive Tuberculosis: An Observational Study in Hyderabad/India." PLoS One 10. no. 9 (2015)
  Grozdanovic, Z., L. C. Berrocal-Almanza, Surabhi Goyal, A. Hussain, T. E. Klassert, D. Driesch, V. Tokaryeva, Y. Löschmann, G. Sumanlatha, N. Ahmed, V. Valluri, R. R. Schumann, B. Lala, and H. Slevogt
  (See online at https://doi.org/10.1371/journal.pone.0138070)
• "Genome-Based Comparison of c-di-GMP Signaling in Pathogenic and Commensal Escherichia coli Strains." Journal of Bacteriology 198, no. 1 (2015): 111-26
  Povolotsky, T. L., and R. Hengge
  (See online at https://doi.org/10.1128/JB.00520-15)
• "Mammalian Lipoxygenases and Their Biological Relevance." Biochimica et Biophysica Acta 1851, no. 4 (2015): 308-30
  Kühn, H., S. Banthiya, and K. van Leyen
  (See online at https://doi.org/10.1016/j.bbalip.2014.10.002)
• "Matrix Metalloproteinase-9 Polymorphism 1562 C > T (Rs3918242) Associated with Protection against Placental Malaria." American Journal of Tropical Medicine and Hygiene 93, no. 1 (2015): 186-188
  Apoorv, T. S., P. P. Babu, S. Meese, P. P. Gai, G. Bedu-Addo, and F. P. Mockenhaupt
  (See online at https://doi.org/10.4269/ajtmh.14-0816)
• "Secreted Lipoxygenase from Pseudomonas aeruginosa Exhibits Biomembrane Oxygenase Activity and Induces Hemolysis in Human Red Blood Cells." Arch Biochem Biophys 584, (2015): 116-24
  Banthiya, S., M. Pekarova, H. Kühn, and D. Heydeck
  (See online at https://doi.org/10.1016/j.abb.2015.09.003)
• "Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue." PLoS One 10, no. 8 (2015): e0137108
  Fatykhova, D., A. Rabes, C. Machnik, K. Guruprasad, F. Pache, J. Berg, M. Toennies, T. T. Bauer, P. Schneider, M. Schimek, S. Eggeling, T. J. Mitchell, A. M. Mitchell, R. Hilker, T. Hain, N. Suttorp, S. Hippenstiel, A. C. Hocke, and B. Opitz
  (See online at https://doi.org/10.1371/journal.pone.0137108)
• "The C-Type Lectin Receptor Mincle Binds to Streptococcus pneumoniae but Plays a Limited Role in the Anti-Pneumococcal Innate Immune Response." PLoS One 10, no. 2 (2015): e0117022
  Rabes, A., S. Zimmermann, K. Reppe, R. Lang, P. H. Seeberger, N. Suttorp, M. Witzenrath, B. Lepenies, and B. Opitz
  (See online at https://doi.org/10.1371/journal.pone.0117022)
• "Toll-Like Receptor 1 Variations Influence Susceptibility and Immune Response to Mycobacterium tuberculosis.” Tuberculosis 95, no. 3 (2015): 328-335
  Dittrich, N., L. C. Berrocal-Almanza, S. Thada, S. Goyal, H. Slevogt, G. Sumaniatha, A. Hussain, S. Sur, S. Burkert, D.-Y. Oh, V. Valluri, R. R. Schumann, and M. L. Conrad
  (See online at https://doi.org/10.1016/j.tube.2015.02.045)
• (2015). Genomic variability in the control of the signaling molecule cyclic-di-GMP and its role in pathogenicity and biofilm formation of commensal and pathogenic Escherichia coli. (Belin: Freie Universität)
  Povolotsky, T.L.
  
• (2015). Impact of genetic host factors on the in vitro growth of Plasmodium falciparum and the innate immune response towards infected red blood cells. (Berlin: Freie Universität)
  Meese, S.
  
• (2015). Monocytes and Macrophages as Determinants of Susceptibility to Infection in Lymphatic Filariasis. (Berlin: Freie Universität)
  O’Regan, N.L.
  
• (2015). ST2 and IL-33 differentially regulate the innate immune response to Streptococcus pneumoniae. (Berlin: Freie Universität)
  Rabes, A.
  
• (2015). The impact of the serum levels of soluble receptor for glycation end products (sRAGE) and its ligand S100A12 for the course and extent of lung involvement in smear positive pulmonary tuberculosis in a cohort study in Hyderabad/ India. (Berlin: Freie Universität)
  Berrocal-Almanza, L.C.
  
• (2015). Variationen der Toll-like Rezeptoren beeinflussen die Suszeptibilität für Tuberkulose in Hyderabad, Indien und die Immunantwort auf Mycobacterium tuberculosis. (Berlin: Freie Universität)
  Dittrich, N.
  
• "Diplomatic Assistance: Can Helminth-Modulated Macrophages Act as Treatment for Inflammatory Disease?" PloS Pathogens 12(4): e1005480
  Steinfelder, S., N. L. O'Regan, and S. Hartmann
  (See online at https://doi.org/10.1371/journal.ppat.1005480)
• "MicroRNAs Constitute a Negative Feedback Loop in Streptococcus pneumoniae Induced Macrophage Activation." Journal of Infectious Diseases, 2016 Jul 15;214(2):288-99
  Griss, K., W. Bertrams, A. Sittka-Stark, K. Seidel, C. Stielow, S. Hippenstiel, N. Suttorp, M. Eberhardt, J. Wilhelm, J. Vera, and B. Schmeck
  (See online at https://doi.org/10.1093/infdis/jiw109)
• (2016). hBD-2 and hBD-3 are induced in S. pneumoniae infected human macrophages via distinct signaling pathways but exhibit similar immune modulatory functions. (Berlin: Freie Universität)
  Wittig, M.
  
• Peripheral blood mononuclear cell microRNA expression in severe lung infections. (Berlin: Freie Universität) 2016
  Griß, K.