Institut für Medizinische Mikrobiologie und Krankenhaushygiene

Forschung

Forschungsgruppen

Pathogenicity of multidrug-resistant Gram-negative bacteria (Göttig)

Göttig Lab

Our research focuses on antibiotic resistance mechanisms and virulence factors of clinically relevant Gram-negative bacteria. Resistance to antibiotics has dramatically increased in recent years, especially among Gram-negative bacteria such as Klebsiella pneumonia, Escherichia coli or Acinetobacter baumannii. Multidrug resistance is often caused by acquisition of bacterial enzymes which are encoded on mobile genetic elements (e.g., plasmid-encoded carbapenemase genes). Highly pathogenic bacteria that are non-susceptible to last-line antibiotics like carbapenems or polymyxins pose a major threat to public health. These bacteria cause severe nosocomial infections like sepsis or pneumonia and can be transmitted from patient to patient. 

Therefore, we are interested in characterizing 

  • molecular mechanisms by which Gram-negative bacteria become resistant to carbapenems, hydroxyquinolines and colistin
  • the molecular evolution of carbapenemases like the New Delhi metallo-beta-lactamase (NDM)
  • how antibiotic resistance genes can be transmitted by horizontal gene transfer in vitro and in vivo
  • the impact of antimicrobial resistance on fitness and virulence of Gram-negative bacteria
  • the pathogenicity factor Acinetobacter trimeric autotransporter adhesin of A. baumannii

Group Leader 


Prof. Dr. med. Dr. rer. physiol. Stephan Göttig
stephan.goettig@unimedizin-ffm.de

Lab members


Dr. Tobias Appel
Zara Dogan
Monika Doll
Anna-Lena Hesse
Lena Ilievski
Luisa Langhoff
Malin Lauer
Amanda Muscheler
Bettina Stietz
Sara Garcia Torres

Funding

Selected Publications

Cacace E, Tietgen M, Steinhauer M, Mateus A, Schultze TG, Eckermann M, Galardini M, Varik V, Koumoutsi A, Parzeller JJ, Corona F, Orakov A, Knopp M, Brauer-Nikonow A, Bork P, Romao CV, Zimmermann M, Cloetens P, Savitski MM, Typas A, Göttig S. 
Uncovering nitroxoline activity spectrum, mode of action and resistance across Gram-negative bacteria. 
Nat Commun. 2025 Apr 22;16(1):3783. doi.org/10.1038/s41467-025-58730-5

Vaidya S, Saha D, Rode DKH, Torrens G, Hansen MF, Singh PK, Jelli E, Nosho K, Jeckel H, Göttig S, Cava F, Drescher K. 
Bacteria use exogenous peptidoglycan as a danger signal to trigger biofilm formation. 
Nat Microbiol. 2025 Jan;10(1):144-157. doi.org/10.1038/s41564-024-01886-5

Sommer J, Reiter H, Sattler J, Cacace E, Eisfeld J, Gatermann S, Hamprecht A, Göttig S. 
Emergence of OXA-48-like producing Citrobacter species, Germany, 2011 to 2022. 
Euro Surveill. 2024 Apr;29(15):2300528. doi.org/10.2807/1560-7917.ES.2024.29.15.2300528

Cacace E, Kim V, Varik V, Knopp M, Tietgen M, Brauer-Nikonow A, Inecik K, Mateus A, Milanese A, Mårli MT, Mitosch K, Selkrig J, Brochado AR, Kuipers OP, Kjos M, Zeller G, Savitski MM, Göttig S, Huber W, Typas A. 
Systematic analysis of drug combinations against Gram-positive bacteria. 
Nat Microbiol. 2023 Nov;8(11):2196-2212. doi.org/10.1038/s41564-023-01486-9

Hamprecht A, Sattler J, Noster J, Stelzer Y, Fuchs F, Dorth V, Gatermann SG, Göttig S. 
Proteus mirabilis - analysis of a concealed source of carbapenemases and development of a diagnostic algorithm for detection. 
Clin Microbiol Infect. 2023 Sep;29(9):1198.e1-1198.e6. doi.org/10.1016/j.cmi.2023.05.032

Leukert L, Tietgen M, Krause FF, Schultze TG, Fuhrmann DC, Debruyne C, Salcedo SP, Visekruna A, Wittig L, Göttig S. 
Infection of Endothelial Cells with Acinetobacter baumannii Reveals Remodelling of Mitochondrial Protein Complexes.
Microbiol Spectr. 2023 Jun 15;11(3):e0517422. doi.org/10.1128/spectrum.05174-22

Sommer J, Gerbracht KM, Krause FF, Wild F, Tietgen M, Riedel-Christ S, Sattler J, Hamprecht A, Kempf VAJ, Göttig S. 
OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamase From Escherichia coli. 
Front Microbiol. 2021 May 12;12:660094. doi.org/10.3389/fmicb.2021.660094

Tietgen M, Leukert L, Sommer J, Kramer JS, Brunst S, Wittig I, Proschak E, Göttig S. 
Characterization of the novel OXA-213-like β-lactamase OXA-822 from Acinetobacter calcoaceticus. 
J Antimicrob Chemother. 2021 Feb 11;76(3):626-634. doi.org/10.1093/jac/dkaa488

Pseudomonas / Cystic Fibrosis (Hogardt)

A selection of our research results can be found here: PUBMED

If you are interested in bacteria, mutants, protocols, or related materials, please submit a formal request via email. We welcome collaboration opportunities.

Epidemiology, antibiotic resistance and laboratory diagnostics of cystic fibrosis (CF) related pathogens

1. Pseudomonas aeruginosa

P. aeruginosa is the major pathogen in chronic CF lung infection. Our research focuses on the epidemiology of multi-resistant P. aeruginosa in CF, with a particular emphasis on the population structure, the occurrence and distribution of resistance markers and the activity of new antibiotics (e.g. cefiderocol) that may combat drug-resistant P. aeruginosa variants. We are also in particular interested in the metabolic adaptation of P. aeruginosa to the CF lung and the contribution of isocitrate dehydrogenase. One current project addresses the anti-pseudomonal activity of high-level concentrations as reached by inhalative administration (e.g. of tobramycin, levofloxacin, colistin and aztreonam). Another ongoing project focuses on the (early/sensitive) detection of P. aeruginosa directly from respiratory secretions of people with CF by molecular methods such as PCR in order to improve the (routine) laboratory diagnostics in CF as the sensitivity of the current gold standard (culture) has limitations. 

2. Burkholderia cepacia complex

Burkholderia cepacia complex (BCC) is one of the most feared pathogens among pwCF, due to its great clinical impact. Similarly to P. aeruginosa, we work on the epidemiology of BCC in CF, with a particular emphasis on the population structure (species distribution, core genome multi locus sequence typing, risk of in-hospital transmission) and the activity of newly available antibiotics (e.g. ceftazidime/avibactam, cefiderocol) and the occurrence of resistance markers. In BCC, antimicrobial therapy is most notably challenging, as no standard regime exists. In this context, we work on the synergy of antibiotic combinations and the detection of resistance mechanisms against new antibiotics. 

Regarding CF microbiology our research interest is closely related to the tasks of the German consiliary laboratory on CF Bacteriology.

3. Clinical Microbiology and other CF pathogens

In addition, our clinical research group continuously works on different aspects of clinical microbiology regarding mainly the epidemiology, clinical relevance of different microbial (cystic fibrosis) pathogens (e.g. mycobacteria, Achromobacter spp.), antibiotic resistances and laboratory diagnostic methods in cooperation with clinical colleagues, microbiologists and reference laboratories (see publication track in PUBMED).

Selected Publications

CF Microbiology:

  1. Kenna D and Hogardt M. Chapter 12: Detection Methods – Bacteria. ECFS book: Inflammation and Infection. Editor: Schwarz C. 2023 European Cystic Fibrosis Society. ISBN: 978-87-975344-0-3. Link: www.ecfs.eu/sites/default/files/publications-free-access-articles/240430_ECFS_book-SAVE.pdf.
  2. Schwarz C, Bend J, Hebestreit H, Hogardt M, Hügel C, Illing JS, Mainz JG, Rietschel E, Schmidt S, Schulte-Hubbert B, Sitter H, Wielpütz J, Hammermann J. S3-Leitlinie „Lungenerkrankung bei Mukoviszidose“ Pseudomonas aeruginosa. 2023, AWMF-Register Nr. 026/022 Link: register.awmf.org/de/leitlinien/detail/026-022.
  3. Hogardt M and Besier S. Microbiology, cross-infection and hygiene in Cystic Fibrosis. European Respiratory Society (ERS) Handbook of Paediatric Respiratory Medicine. Edited by Ernst Eber and Fabio Midulla. Book | 2021 ISBN (electronic): 978-1-84984-131-3. DOI: 10.1183/9781849841313.eph01.
  4. Wetzstein N, Diricks M, Kohl TA, Wichelhaus TA, Andres S, Paulowski L, Schwarz C, Lewin A, Kehrmann J, Kahl BC, Dichtl K, Hügel C, Eickmeier O, Smaczny C, Schmidt A, Zimmermann S, Nährlich L, Hafkemeyer S, Niemann S, Maurer FP, Hogardt M. Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients. Microbiol Spectr. 2022 Aug 31;10(4):e0171422. DOI: 10.1128/spectrum.01714-22.
     

Clinical Microbiology:

  1. Kessel J, Bug G, Steffen B, Brunnberg U, Vehreschild MJGT, Weber S, Scheich S, Lang F, Serve H, Herrmann E, Hogardt M. Risk factors and outcome of Pseudomonas aeruginosa bloodstream infections (PABSI) in hematological patients: a single center retrospective cohort study. Infection. 2025 Aug:53(4):1383-1392. DOI: 10.1007/s15010-024-02453-0.
  2. Spiehl D, Schwall G, Post F, Weber C, Dörsam E, Blaeser A, Kempf VAJ, Hogardt M. Printed dry and ready-to-use in vitro diagnostic culture media devices for differentiation and antimicrobial susceptibility testing of bacteria, Biosensors and Bioelectronics: X, Volume 21, 2024,100557. DOI: 10.1016/j.biosx.2024.100557.
  3. Weber C, Schultze T, Göttig S, Kessel J, Schröder A, Tietgen M, Besier S, Burbach T, Häussler S, Wichelhaus TA, Hack D, Kempf VAJ, Hogardt M. Antimicrobial activity of Ceftolozane-Tazobactam, Ceftazidime-Avibactam and Cefiderocol against multidrug-resistant P. aeruginosa recovered at a German university hospital. Microbiol Spectr. 2022 Oct 26;10(5):e0169722. DOI: 10.1128/spectrum.01697-22.
  4. Kessel J, Bender J, Werner G, Griskaitis M, Herrmann E, Lehn A, Serve H, Zacharowski K, Zeuzem S, Vehreschild MJGT, Wichelhaus TA, Kempf VAJ, Hogardt M. Risk factors and outcomes associated with the carriage of tigecycline- and vancomycin-resistant Enterococcus faecium. J Infect. 2021; 82(2):227-234. DOI: 10.1016/j.jinf.2020.12.003.


Members of the group (2026):

Prof. Dr. med. Michael HogardtMichael.Hogardt@unimedizin-ffm.de
Dr. med. Tobias BurbachTobias.Burbach@unimedizin-ffm.de
Dr. hum. biol. Maria WilleMaria.Wille@unimedizin-ffm.de
Annette SchröderAnnette.Schröder@unimedizin-ffm.de
Abenayaa Vijashankar 

Medical doctoral students:

cand. med. Tabea Schnurbusch 
cand. med. Laura Barz 
cand. med. Klara Brößner 
cand. med. Jannes Hulsman 

Konsiliarlabor Mukoviszidose-Bakteriologie:

E-Mail: NKL-MukoviszidoseBak@unimedizin-ffm.de 

Homepage: Konsiliarlabor Mukoviszidose-Bakteriologie

Bartonella (Kempf)

Our latest research results can be found here: PUBMED

If you are interested in bacteria, mutants, cells, antibodies, monoclonal antibodies, protocols, or related materials, please submit a formal request via email. We welcome collaboration opportunities.

1. Pathogenicity of Bartonella henselae : Bacterial adhesion and angiogenic reprogramming

Our research focuses on the interaction between Bartonella henselae and endothelial cells, as well as components of the extracellular matrix, with particular emphasis on the bacterium’s ability to trigger angiogenic processes. A key part of our work is the structural and functional characterization of Bartonella adhesin A (BadA), which serves as the prototype for a relatively new class of bacterial adhesins known as “trimeric autotransporter adhesins” (TAAs). These adhesins act as major virulence factors in many Gram-negative bacteria. Current studies aim to analyze the relationship between specific domains of BadA and their functions in mediating adhesion to matrix proteins and host cells, as well as in inducing angiogenic gene expression programs, including HIF-1 and VEGF.

Selected publications:

  1. Thibau, A., Vaca, D. J., Bagowski, M., Hipp, K., Bender, D., Ballhorn, W., Linke, D., Kempf, V.A.J. Adhesion of Bartonella henselae to fibronectin is mediated via repetitive motifs present in the stalk of Bartonella adhesin A. Microbiol Spectr. 2022:e0211722. DOI: 10.1128/spectrum.02117-22.
  2. Vaca, D.J., Thibau, A., Leisegang, M., Malmström, J., Linke, D., Eble, J.A., Ballhorn, W., Schaller, M., Happonen, L., Kempf, V.A.J. Interaction with fibronectin represents the molecular basis for Bartonella henselae host cell adhesion. Microbiology Spectrum Journal, 2022: 0(5):e0211722. DOI: 10.1128/spectrum.02117-22.
  3. Linke, D., Riess, T., Autenrieth, I.B., Lupas, A., Kempf, V.A.J.; Trimeric autotransporter adhesins: Variable structure, common function. Trends in Microbiology 2006, 14(6):264-70. DOI: 10.1016/j.tim.2006.04.005.
  4. Riess, T., Andersson, S.G.E., Lupas, A., Schaller, M., Schäfer, A., Kyme, P., Martin, J., Wälzlein, J.-H., Ehehalt, U., Lindroos, H., Schirle, M., Nordheim, A, Autenrieth, I. B., Kempf, V.A.J.; Bartonella adhesin A mediates a proangiogenic host cell response. The Journal of Experimental Medicine 2004, 200(10): 1267-1278. DOI: 10.1084/jem.20040500.
     
Bartonella henselae expressing the long Bartonella adhesin (BadA).
Endothelial cells (red) infected with B. henselae (blue).

2. Pathogenicity of Bartonella bacilliformis

Since 2018, we have been investigating the pathogenicity of Bartonella bacilliformis, the causative agent of hemolytic Oroya fever—a neglected tropical disease with a lethality rate of up to 90% if left untreated. Our research is conducted in close collaboration with our Peruvian partners at the Universidad Nacional Mayor de San Marcos and the Universidad Peruana Cayetano Heredia, both based in Lima. The projects aim to elucidate the mechanisms of hemolysis and to characterize adhesin-mediated erythrocyte binding. To this end, we have developed markerless gene deletion techniques, cloning strategies, and several infection models including erythrocytes, endothelial cells, and Galleria mellonella.

Selected publications:

  1. Dichter, A.A., Winklmeier, F., Munteh, D., Ballhorn, W., Becker, S.A., Averhoff, B., Bonig, H., Goldman, A., García-Quintanilla, M., Solis, L., Tsukayama, P., Kempf, V.A.J. Porin A and α/β-hydrolase are necessary and sufficient for hemolysis induced by Bartonella bacilliformis. Nature Communications 2025 (in press).
  2. Dichter, A., Schultze, T.G., Becker, S.A., Tsukayama, P., Kempf, V.A.J. Complete genome sequence of Bartonella bacilliformis strain KC584 (ATCC® 35686™). Microbiology Resource Announcements, 2019, 2;9(1). pii: e01377-19. DOI: 10.1128/MRA.01377-19.
  3. Garcia-Quintanilla, M., Dichter, A., Guerra H., Kempf, V.A.J.Carrion´s disease: more than a neglected disease. Parasites & Vectors, 2019, 26;12(1):141. DOI: 10.1186/s13071-019-3390-2.
     
Bartonella bacilliformis expressing long flagella.
Human erythrocyte infected with B. bacilliformis.

3. Epidemiology of Bartonella spp.

The epidemiology of Bartonella spp. infections is studied through environmental investigations using advanced next-generation sequencing (NGS)-based DNA detection and microbiome analysis. In addition, seroepidemiological studies are performed, with a special focus on Bartonella schoenbuchensis, the causative agent of deer ked dermatitis.

Selected publications:

  1. Buntrock, K.N., Ballhorn, W., Podlich, H., Malmström, H., Happonen, L., Chowdhury, S., Hipp, K., Schaller, M., Jurke, A., Kempf, V.A.J. Immunofluorescence analysis reveals no increased seroprevalence of anti-Bartonella schoenbuchensis-IgG antibodies in German forest workers. Parasites & Vectors, 2025 18(1):332. DOI: 10.1186/s13071-025-06856-2.
  2. Regier, Y., Komma, K., Weigel, M., Pulliainen A.T., Göttig, S., Hain, T., Kempf, V.A.J. Microbiome analysis reveals the presence of Bartonella spp. and Acinetobacter spp. in deer keds (Lipoptena cervi). Frontiers in Microbiology. 2018, 20;9:3100. DOI: 10.3389/fmicb.2018.03100
     
Vero cells infected with Bartonella schoenbuchensis.
Microbiome analysis of deer keds detecting B. schoenbuchensis.

4. Development of laboratory diagnostic tools 

We are committed to translating our findings from basic research into applied science through collaborations with industrial partners. Several serological assays have been developed to date, and molecular diagnostic tools are continuously being refined.

Selected publications:

  1. Dichter, A.A., Schultze, T.G., Wenigmann, A., Ballhorn, W., Latz, A., Ventosilla Lopez, P., Guerra Allison, H., Ugarte, C.A., Tsukayama, P., Kempf, V.A.J. Identification of immunodominant Bartonella bacilliformis proteins: a combined in silico and serology approach. Lancet Microbe 2021 Dec;2(12):e685-e694. DOI: 10.1016/S2666-5247(21)00184-1.
  2. Jost, M., Latz, A., Ballhorn, W., Kempf, V.A.J. Development of a specific and sensitive ELISA as an in-vitro diagnostic tool for the detection of Bartonella henselae antibodies in human serum. J Clin Microbiol 2018 27;56(12). DOI: 10.1128/JCM.01329-18.
     
Example of an ELISA-based diagnostic tool for the detection of anti-B. bacilliformis-antibodies.

Monoklonale Antikörper / Monoclonal antibodies

Wir können murine monoklonale Antikörper gegen Bartonella henselae, Stamm Marseille (hergestellt im Jahr 2000), bereitstellen. Alle Klone wurden im Jahr 2026 erneut getestet und ihre Reaktivität mittels Immunfluoreszenz und Western Blot bestätigt (pdf). Wenn Sie an diesen Hybridomen (basierend auf AGS-8-Zellen) interessiert sind, stellen wir diese Ihrem Labor gerne zur Verfügung. Der Transport muss organisiert werden. Die Zusammenarbeit mit Industriepartnern erfolgt auf Grundlage eines zu definierenden Vertragsrahmens, für akademische Einrichtungen können Kooperationsvereinbarungen geschlossen werden. 

We will distribute murine monoclonal antibodies against Bartonella henselae, strain Marseille (generated in the year 2000). All clones have freshly been re-tested in 2026 for reactivity in immunofluorescence and western blotting (pdf). If you are interested in these hybridomas (based on AGS-8 cells), we will be happy to give these to your laboratory. The transport has to be organized. Collaboration with industry partners will be based on a contractual framework to be defined, whereas cooperation agreements may be established with academic institutions.

 

  Members of the group (2026):

Univ.-Prof. Dr. med. Volkhard KempfVolkhard.Kempf@unimedizin-ffm.de
Dr. Susanne GottfriedSusanne.Gottfried@unimedizin-ffm.de
Wibke Ballhornballhorn@med.uni-frankfurt.de
Dr. Diana Vacavacallerena@med.uni-frankfurt.de
Camilla CadoliCamilla.Cadoli@unimedizin-ffm.de

  Medical doctoral students (2026):

cand. med. Maximilian Schultheis    schultheis.maximilian@t-online.de
cand. med. Felix Burckhardtfelixmichael.burckhardt@gmail.com
cand. med. Akin Cebiakin.cebi@stud.uni-frankfurt.de
cand. med. Aristotelis Routsiaristotelis.routsi@stud.uni-frankfurt.de

 

Borrelia (Kraiczy)

Our latest publications can be found here: PUBMED

Important review articles are: 

Adamu, A., Reyer, F., Lawal, N., Hassan, A. J., Imam, M. U., Bello, M. B., and P. Kraiczy. Aetiologies of bacterial tick-borne febrile illnesses in humans in Africa: Diagnostic limitations and the need for improvement. Front. Med. 2024, 11:1419575. doi: 10.3389/fmed.2024.1419575.

Lin, Y.P., Diuk-Wasser, M., Stevenson, B., and P. Kraiczy. Complement evasion contributes to Lyme borreliae host association. Trends Parasitol. 2020, 16:634-645. doi: 10.1016/j.pt.2020.04.011.

Röttgerding, F., and P. Kraiczy. Immune evasion strategies of relapsing fever spirochetes. Front. Immunol. 2020, 11:1560. doi: 10.3389/fimmu.2020.01560.

1. Immune escape strategies of Borrelia : Interaction with the human complement system

Our research focuses on immune evasion and pathogenesis of Borrelia species, the etiologic agents of Lyme borreliosis and relapsing fever. A central part of this project deals with the phenotypic characterisation of newly discovered Borrelia species towards their natural resistance to human serum. Our investigations also include the identification and functional characterisation of complement-interacting proteins allowing Borrelia to inhibit complement-mediated bacteriolysis.

Selected publications:

  1. Brangulis, K., Sürth, V., Marcinkiewicz, A. L.; Akopjana, I., Kazaks, A., Bogan, J., Huber, A., Lin, Y.-L., and P. Kraiczy. CspZ variant-specific interaction with Factor H incorporates a metal site to support Lyme borreliae complement evasion. J. Biol. Chem. 2025, 1:108083, doi: 10.1016/j.jbc.2024.108083.
  2. Walter, L., Sürth V., Röttgerding F., Zipfel, P.F., Fritz-Wolf, K., and P. Kraiczy. Elucidating the immune evasion mechanisms of Borrelia mayonii, the causative agent of Lyme disease. Front Immunol. 2019, 10:2722, doi: 10.3389/fimmu.2019.02722.
  3. Röttgerding F., Wagemakers, A., Koetsveld, J., Fingerle, V., Kirschfink, M., Hovius, J.W.R., Zipfel, P.F., Wallich, R., and P. Kraiczy. Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties. Sci. Rep. 2017, 7:303. doi: 10.1038/s41598-017-00412-4.

 

Left: Borrelia cells covered with activated complement components.
Right: Structure of a complement-inhibitory protein of Borrelia recurrentis.

2. Interaction of relapsing fever Borrelia species with host-derived proteins

Additional projects aim to elucidate the molecular interactions between relapsing fever Borrelia species and key host-derived proteins implicated in fibrinolysis and bacterial adhesion. These studies comprise in depth biochemical analyses of the interaction between relapsing fever borrelial proteins with human plasminogen and fibronectin. From these studies, we expect important contributions towards our understanding of the pathogenesis of relapsing fever Borrelia in the human host.

Selected publications:

  1. Damm, A.-S., Reyer, F., Langhoff, L., Lin, Y.-P., Falcone, F.H. and P. Kraiczy. Multifunctional interaction of CihC/FbpC orthologs of relapsing fever spirochetes with host-derived proteins involved in adhesion, fibrinolysis, and complement evasion. Front. Immunol. 2024, 15:1390468, doi: 10.3389/fimmu.2024.1390468.
  2. Schmidt, F.L., Sürth, V., Berg, T.K., Lin, Y.-P., Hovius, J.W., and P. Kraiczy. Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 of with plasminogen and complement. Sci. Rep. 2021, 11:4964. doi: 10.1038/s41598-021-84533-x.
  3. Nguyen, N.T.T., Röttgerding F., Devraj, G., Lin, Y.-P., Koenigs, A., and P. Kraiczy. The complement binding and inhibitory protein CbiA of Borrelia miyamotoi degrades extracellular matrix components by interacting with plasmin(ogen). Front. Cell Infect Microbiol. 2018, 8:23. doi: 10.3389/fcimb.2018.00023.

 

Left: Binding of fibronectin to borrelial proteins. Middle: Binding of plasminogen to borrelial proteins. Right: Conversion of protein-bound plasminogen to proteolytically active plasmin.

3. Borrelia interactions with the blood–brain barrier (Diana Vaca)

Lyme disease and relapsing fever are vector-transmitted bacterial infections with strictly vector-associated geographic distributions. Under certain conditions, both infections can disseminate to the central nervous system, resulting in meningitis, encephalopathy and long-term cognitive dysfunction. This project aims to examine the mechanisms that enable neuroinvasive Borrelia to cross the blood-brain barrier (BBB), and the specific bacterial and host factors involved in this process. We employ in vitro models that mimic structural and functional features of the human BBB to investigate at a mechanistic level Borrelia adhesion and disruption of the BBB. 

Selected publications:

  1. Vaca, D. J., Frenzel, F., Torres, S., Leisegang, M. S., Günther, S., Bender, D., Kraiczy, P., Göttig, S., and V. A. J. Kempf. Adhesion of human pathogenic bacteria to endothelial cells is mediated by fibronectin. Microb. Infect. 2023, 25:105172, doi: 10.1016/j.micinf.2023.105172.
  2. Vaca, D.J., Thibau, A., Schütz, M., Kraiczy, P., Happonen, L., Malmström, J., and V.A.J. Kempf. Interaction with the host: the role of fibronectin and extracellular matrix proteins in the adhesion of Gram-negative bacteria. Med. Microbiol. Immunol., 2020, 209:277-299, doi: 10.1007/s00430-019-00644-3.
Left: Human brain microvascular endothelial cell model depicting the tight junction-associated protein ZO-1 (Zonula Occludens-1).
Right: Borrelia adhesion to brain microvascular endothelial cells.

4. Development of immunoassays for the diagnosis of louse-borne relapsing fever 

Louse-borne relapsing fever is an epidemic vector-borne disease associated with high mortality, yet reliable in vitro diagnostic tools remain currently unavailable. This project focuses on the development and optimisation of immunoassays exhibiting high specificity and sensitivity. These studies are conducted in close collaboration with African partners from Kenya (Dr. John Nijeru, Kenya Medical Research Institute (KEMRI), Nairobi) and from Nigeria (Prof. Mustapha Imam, Federal University Teaching Hospital, Lafia). 

Selected publications:

  1. Reyer, F., Olesiuk, O., Röttgerding, F., Fingerle, V., Adamu, A., Waithiru, D., Njeru, J., and P. Kraiczy. Serological evidence of louse-borne relapsing fever in northern Kenya. Travel Med. Infect. Dis. 2024, 59:102714, doi: 10.1016/j.tmaid.2024.102714.
  2. Röttgerding, F., Njeru, J., Schlüfter, E., Latz, A., Mahdavi, R., Steinhoff, U., Cutler, S., Besier, S., Kempf, V.A.J., Fingerle, V., and P. Kraiczy. Novel approaches for the serodiagnosis of louse-borne relapsing fever. Front. Cell. Infect. Microbiol. 2022, 12:983770, 
    doi: 10.3389/fcimb.2022.983770.
Prototype of a line blot immunoassay for the detection of anti-Borrelia recurrentis-antibodies.


Members of the group (2025):

Prof. Dr. phil. nat. Peter KraiczyKraiczy@em.uni-frankfurt.de
Dr. rer. nat. Diana Vacavacallerena@med.uni-frankfurt.de
Nadine Duschek 
Flavia Reyer 

 
Medical doctoral student:

Daniela Fricker 

 

Epidemiologie und Prävention nosokomialer Infektionen (Reinheimer)

Das Ziel der Arbeitsgruppe ist es, durch die Analyse der Epidemiologie nosokomialer Infektionen gezielte infektionspräventive Maßnahmen zu entwickeln und diese zu evaluieren. Dazu gehört beispielsweise die Analyse von Infektionshäufungen und der nachfolgend eingeleiteten Maßnahmen. Weitere Untersuchungen betreffen die Analyse von Risikofaktoren  für die Übertragung nosokomialer Infektionserreger, speziell multiresistenter Erreger.

Arbeitsgruppenleiterin:

Prof. Dr. med. Claudia Reinheimer
claudia.reinheimer(at)unimedizin-ffm.de

Spread of Multidrug-Resistant Bacteria: Molecular Mechanisms and Targeted Interventions (Sommer)

Infections caused by antibiotic-resistant bacteria are a major threat to patients and cause millions of deaths worldwide each year. The spread of antibiotic resistant bacteria is directly linked to the exchange of antibiotic resistance genes between different bacterial species. Our group seeks to understand the mechanisms of antibiotic resistance gene spread in order to develop new strategies to limit the impact of antibiotic resistant bacteria on global health.

We are particularly interested in:

  • Epidemiology of carbapenem-resistant Gram-negative bacteria
  • Molecular mechanisms that promote the exchange of antibiotic resistance genes between different bacterial species and in complex bacterial communities.
  • Dissemination of antibiotic resistance genes in human microbiomes and interactions between microbiome diversity and the spread of resistance genes
  • Culture-based microbiology methods, e.g. antibiotic susceptibility testing, growth kinetics and fitness assays
  • in vitro and in vivo models of infection
  • Next-generation sequencing, including Oxford Nanopore and Illumina sequencing technologies and bespoke bioinformatics for whole genome and metagenome sequencing approaches and specialised sequencing data analysis.

Methods and technologies we use in our research:

  • Culture-based microbiology methods, e.g. antibiotic susceptibility testing, growth kinetics and fitness assays
  • in vitro and in vivo models of infection
  • Next-generation sequencing, including Oxford Nanopore and Illumina sequencing technologies and bespoke bioinformatics for whole genome and metagenome sequencing approaches and specialised sequencing data analysis.

Group leader:

Dr. med Julian Sommer
Julian.Sommer@med.uni-frankfurt.de
https://orcid.org/0009-0006-3654-2006

Members:

Catharina Joly
Mara Herterich
Marie Welter

Publications:

Sommer J, Reiter H, Sattler J, Cacace E, Eisfeld J, Gatermann S, et al. Emergence of OXA-48-like producing Citrobacter species, Germany, 2011 to 2022. Eurosurveillance. 2024 Apr 11;29(15):2300528.

Sattler J, Noster J, Stelzer Y, Spille M, Schäfer S, Xanthopoulou K, et al. OXA-48-like carbapenemases in Proteus mirabilis - novel genetic environments and a challenge for detection. Emerg Microbes Infect. 2024 Dec;13(1):2353310.

Sattler J, Tsvetkov T, Stelzer Y, Schäfer S, Sommer J, Noster J, et al. Emergence of Tn 1999.7, a New Transposon in blaOXA-48 -Harboring Plasmids Associated with Increased Plasmid Stability. Antimicrob Agents Chemother. 2022 Nov 15;66(11):e00787-22.

Sommer J, Gerbracht KM, Krause FF, Wild F, Tietgen M, Riedel-Christ S, et al. OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamase From Escherichia coli. Frontiers in Microbiology. 2021 May 12;12(May):1–9.

Göttig S, Walker SV, Saleh A, Koroska F, Sommer J, Stelzer Y, et al. Comparison of nine different selective agars for the detection of carbapenemase-producing Enterobacterales (CPE). European Journal of Clinical Microbiology and Infectious Diseases. 2020 May 1;39(5):923–7.

Hamprecht A, Sommer J, Willmann M, Brender C, Stelzer Y, Krause FF, et al. Pathogenicity of Clinical OXA-48 Isolates and Impact of the OXA-48 IncL Plasmid on Virulence and Bacterial Fitness. Frontiers in Microbiology. 2019 Nov 1;10:2509.

Koroska F, Göttig S, Kaase M, Steinmann J, Gatermann S, Sommer J, et al. Comparison of phenotypic tests and an immunochromatographic assay and development of a new algorithm for detection of OXA-48-like carbapenemases. Journal of Clinical Microbiology. 2017;55(3):877–83.

Funding

Antimicrobial Resistance & Microbial Pathogenicity (Wichelhaus)

Infectious diseases are of central medical importance despite promising innovations in the field of diagnostics and therapy. The COVID-19 pandemic has demonstrated that infectious agents can pose a substantial threat not only to health, but also to social cohesion, the economy and freedom. Infectious agents also know how to successfully evade antiinfectives by establishing resistance mechanisms. Antibiotics are among the most important medical achievements and are indispensable in modern medicine. They are used to treat bacterial infections in human and veterinary medicine. However, more and more pathogens are becoming resistant to the active substances.

Learn more about the causes and relevance of antibiotic resistance and strategies to counteract the development of resistance.

Antibiotics - the sword in the fight against infectious agents is becoming blunt. (Lecture at the Health Forum of the University Hospital Frankfurt)

 1. Multidrug-resistant bacteria: Epidemiology and molecular mechanisms of antibiotic resistance

Colonisation/infection with multidrug-resistant bacteria (MDRB) such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), cefixime- and azithromycin-resistant Neisseria gonorrhoeae, extended-spectrum beta-lactamase (ESBL)- producing Enterobacterales, carbapenemase-producing Gram-negative pathogens and, last but not least, multidrug-resistant mycobacteria is a growing problem worldwide. Our research focuses on molecular mechanisms of resistance and epidemiology of MDRB.

2. Evaluation and development of new antimicrobials

The alarming increase of antibiotic-resistant bacterial pathogens points to the need for new antiinfective therapies. Consequently, antibiotic resistance has been called one of the world’s most pressing public health problems. A worrisome trend is the spread of carbapenemases (e.g. metallo-β-lactamases) among Gram-negative pathogens that can confer resistance to almost all β-lactams including carbapenems and consequently present a major challenge for treatment of individual patients.

Our research focuses on the development and evaluation of new antimicrobials active against MDRB.

In particular, our research aims at developing a new anti-infective agent by identifying metallo-β-lactamase inhibitors which will restore the bactericidal activity of common β-lactam antibiotics against multidrug-resistant Gram-negative pathogens.

Furthermore, our aim is to develop a much-needed new strategy for the treatment of MDRBs. To this end, we have designed a ‘nitroxoline shuttle’. Nitroxoline is an antibiotic drug that effectively kills a broad variety of bacteria; however, its use is limited to bladder infections due to its inability of reaching other parts of the human body. The ‘shuttle’ is a chemical substance that, when linked to nitroxoline, will allow to safely transport this powerful antibiotic to bacteria in various parts of the human body. In the project, we will manufacture the ‘nitroxoline shuttle’ and carry out tests to characterise its ability to kill bacteria in a targeted manner. This project “Targeted Nitroxoline Delivery for Treatment of Multidrug-resistant Pathogens” (TANDEM) is supported by BMBF under the framework of the JPIAMR – Joint Programming Initiative on Antimicrobial Resistance.

 

Targeted Nitroxoline Delivery for Treatment of Multidrug-resistant Pathogens.

 3. Pathogenicity of multidrug-resistant bacteria

We observed that hematopoietic stem cell transplantation (HSCT) patients colonized by multidrug-resistant bacteria (MDRB) had a higher death rate due to infections in the immediate posttransplant period compared to non-colonized patients.

Our research therefore focuses on the interplay between the immune system and the microbiome. This will allow us to understand if changes in the microbiome are associated with alterations in the cellular immune system. Metabolomic studies will enable us to find potential biomarkers that correlate with a poor microbiome and an altered cellular immune recovery. The obtained data of the microbiome, lymphocyte subpopulations and metabolomics will finally be crossed with clinical data, the colonization status with multidrug-resistant bacteria and outcome data to contribute to the elucidation of higher death rates observed in MDRB-colonized patients with predictive biomarkers.

Publications: Pubmed

 

Funding:

Prof. Dr. Dr. Thomas A. Wichelhaus