Project management: Prof. Dr. Marcus Fulde

Research focus of the "Veterinary Infection Biology" working group

Research into the mechanisms of host-pathogen interactions is the focus of the "Veterinary Infection Biology" working group. We are particularly interested in diseases and pathogens that affect neonates, as neonates still represent a risk group with extremely high morbidity and mortality and very little is known about the pathophysiology of the neonatal host compared to the adult. Our aim is to look at the infection from both sides, i.e. from the bacterium as well as from the host. Therefore, our interests include research into the mechanisms of bacterial virulence factors as well as the influence of the innate immune system on an infection. In order to meet this requirement, we use a very broad spectrum of methods that make use of a wide range of techniques from various scientific disciplines, such as protein biochemistry, microbiology, molecular biology and (infection) immunology. The reservoir of pathogens that we deal with in our studies has a similarly broad spectrum. These include gram-positive agents such as streptococci and listeria, which cause serious systemic diseases (septicemia and/or meningitis) in neonates (both in humans and animals). On the other hand, we deal with representatives of gram-negative Enterobacteriaceae, such as Salmonella Typhimurium. S. Typhimurium is a typical zoonotic pathogen and is one of the most important pathogens causing (self-limiting) gastrointestinal infections worldwide. In the neonatal host, however, S . Typhimurium has a tendency to spread systemically, which can lead to life-threatening septicemia and meningitis, especially in third world countries with low hygiene standards. Another focus of our working group is the phenomenon of bacterial persistence. This is a phenomenon that allows a subpopulation of bacteria to survive treatment with bactericidal antibiotics even without genetically determined resistance mechanisms, thus enabling re-infections. The underlying mechanisms are multifaceted and have been little researched to date. We are trying to make a contribution to this topic.

 

Selected publications:

• Nerlich A, Lapschies AM, Kohler TP, Cornax I, Eichhorn I, Goldmann O, Krienke P, Bergmann S, Nizet V, Hammerschmidt S, Rohde M, Fulde M. Homophilic protein interactions facilitate bacterial aggregation and IgG-dependent complex formation by the Streptococcus canis M protein SCM. Virulence. 2019 Dec;10(1):194-206. doi: 10.1080/21505594.2019.1589362
• Linzner N, Loi VV, Fritsch VN, Tung QN, Stenzel S, Wirtz M, Hell R, Hamilton CJ, Tedin K, Fulde M, Antelmann H. Staphylococcus aureus Uses the Bacilliredoxin (BrxAB)/Bacillithiol Disulfide Reductase (YpdA) Redox Pathway to Defend Against Oxidative Stress Under Infections. Front. Microbiol. 10:1355. doi: 10.3389/fmicb.2019.01355.
• Jagau H, Behrens IK, Lahme K, Lorz G, Köster RW, Schneppenheim R, Obser T, Brehm MA, König G, Kohler TP, Rohde M, Frank R, Tegge W, Fulde M, Hammerschmidt S, Steinert M, Bergmann S. Von Willebrand Factor Mediates Pneumococcal Aggregation and Adhesion in Blood Flow. Front Microbiol. 2019 Mar 26;10:511. doi: 10.3389/fmicb.2019.00511.
• Pägelow D, Chhatbar C, Beineke A, Liu X, Nerlich A, van Vorst K, Rohde M, Kalinke U, Förster R, Halle S, Valentin-Weigand P, Hornef MW, Fulde M. The olfactory epithelium as a port of entry in neonatal neurolisteriosis. Nat Commun. 2018 Oct 15;9(1):4269. doi: 10.1038/s41467-018-06668-2.
• Loi VV, Busche T, Tedin K, Bernhardt J, Wollenhaupt J, Huyen NTT, Weise C, Kalinowski J, Wahl MC, Fulde M, Antelmann H. Redox-Sensing Under Hypochlorite Stress and Infection Conditions by the Rrf2-Family Repressor HypR in Staphylococcus aureus. Antioxid Redox Signal. 2018 Sep 1;29(7):615-636. doi: 10.1089/ars.2017.7354.
• Fulde M, Sommer F, Chassaing B, van Vorst K, Dupont A, Hensel M, Basic M, Klopfleisch R, Rosenstiel P, Bleich A, Bäckhed F, Gewirtz AT, Hornef MW. Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition. Nature. 2018 Aug;560(7719):489-493. doi: 10.1038/s41586-018-0395-5.
• Thompson A, Fulde M, Tedin K. The metabolic pathways utilized by Salmonella Typhimurium during infection of host cells. Environ Microbiol Rep. 2018 Apr;10(2):140-154. doi: 10.1111/1758-2229.12628.
• Zhang K, Riba A, Nietschke M, Torow N, Repnik U, Pütz A, Fulde M, Dupont A, Hensel M, Hornef M. Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo. PLoS Pathog. 2018 Mar 9;14(3):e1006925. doi: 10.1371/journal.ppat.1006925.
• Eichhorn I, Tedin K, Fulde M*. Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhimurium Q1. Genome Announc. 2017 Oct 19;5(42). pii: e01151-17. doi: 10.1128/genomeA.01151-17.
• Braetz S, Schwerk P, Thompson A, Tedin K, Fulde M. The role of ATP pools in persister cell formation in (fluoro)quinolone-susceptible and -resistant strains of Salmonella enterica ser. Typhimurium. Vet Microbiol. 2017 Oct;210:116-123. doi: 10.1016/j.vetmic.2017.09.007.
• Eichhorn I, Jarek M, van der Linden M, Fulde M*. Draft Genome Sequence of the zoonotic Streptococcus canis isolate G361. Genome Announc. 2017 Sep 21;5(38). pii: e00967-17. doi: 10.1128/genomeA.00967-17.
• Bergmann S, Eichhorn I, Kohler TP, Hammerschmidt S, Goldmann O, Rohde M, Fulde M*. SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G. Front Cell Infect Microbiol. 2017 Mar 28;7:80. doi: 10.3389/fcimb.2017.00080.
• Verkühlen GJ, Pägelow D, Valentin-Weigand P, Fulde M*. SCM-positive Streptococcus canis are predominant among pet-associated group G streptococci. Berl Munch Tierarztl Wochenschr. 2016 May-Jun;129(5-6):247-50.
• Zhang K, Dupont A, Torow N, Gohde F, Leschner S, Lienenklaus S, Weiss S, Brinkmann MM, Kühnel M, Hensel M, Fulde M², Hornef MW². Age-dependent enterocyte invasion and microcolony formation by salmonella. PLoS Pathog. 2014 Sep 11;10(9):e1004385. doi: 10.1371/journal.ppat.1004385.
• Fulde M¹, Bernardo-García N¹, Rohde M, Nachtigall N, Frank R, Preissner KT, Klett J, Morreale A, Chhatwal GS, Hermoso JA, Bergmann S. Pneumococcal phosphoglycerate kinase interacts with plasminogen and its tissue activator. Thrombosis and haemostasis. 2014;111(3):401-16. Epub 2013/11/08. doi: 10.1160/th13-05-0421. 
• Fulde M*, Rohde M, Polok A, Preissner KT, Chhatwal GS, Bergmann S. Cooperative plasminogen recruitment to the surface of Streptococcus canis via M protein and enolase enhances bacterial survival. MBio. 2013 Mar 12;4(2):e00629-12.
• Hitzmann A, Bergmann S, Rohde M, Chhatwal GS, Fulde M*. Identification and characterization of the arginine deiminase system of Streptococcus canis. Vet Microbiol. 2013 Feb 22;162(1):270-7
• Fulde M*, Rohde M, Hitzmann A, Preissner KT, Nitsche-Schmitz DP, Nerlich A, Chhatwal GS, Bergmann S. SCM, a novel M-like protein from Streptococcus canis, binds (mini)-plasminogen with high affinity and facilitates bacterial transmigration. Biochem J. 2011 Mar 15;434(3):523-35.

 

Overview articles:

• Doran KS¹, Fulde M¹, Gratz N¹, Kim BJ¹, Nau R¹, Prasadarao N¹, Schubert-Unkmeir A¹, Tuomanen EI¹, Valentin-Weigand P. Host-pathogen interactions in bacterial meningitis. Acta Neuropathol. 2016 Feb;131(2):185-209. doi: 10.1007/s00401-015-1531-z.
• Hornef MW*, Fulde M*. Ontogeny of mucosal immune responses. Frontiers in Immunology, October 2014, doi: 10.3389/fimmu.2014.00474
• Fulde M, Hornef M. Maturation of the enteric mucosal innate immune system during the postnatal period. Immunol Rev. 2014 Jul;260(1):21-34. doi: 10.1111/imr.12190.
• Fulde M, Steinert M, Bergmann S. Interaction of streptococcal plasminogen binding proteins with the host fibrinolytic system. Front Cell Infect Microbiol. 2013 Nov 22;3:85.
• Fulde M*, Valentin-Weigand P*. Epidemiology and pathogenicity of zoonotic streptococci. Curr Top Microbiol Immunol. 2013;368:49-81.

 

Book chapters:

• Fulde M*, Bergmann S* (2017). Impact of Streptococcal Enolase in Virulence, in: Moonlighting proteins – novel virulence factors in bacterial infections. Ed. Brian Henderson; Wiley Blackwell, pp. 245-259