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1. Non-cross-reactive epitopes dominate the humoral immune response to COVID-19 vaccination – kinetics of plasma antibodies, plasmablasts and memory B cells

Author

Wietschel, Kilian A., primary, Fechtner, Kevin, additional, Antileo, Elmer, additional, Abdurrahman, Goran, additional, Drechsler, Chiara A., additional, Makuvise, Michelle Kudzayi, additional, Rose, Ruben, additional, Voß, Mathias, additional, Krumbholz, Andi, additional, Michalik, Stephan, additional, Weiss, Stefan, additional, Ulm, Lena, additional, Franikowski, Philipp, additional, Fickenscher, Helmut, additional, Bröker, Barbara M., additional, Raafat, Dina, additional, and Holtfreter, Silva, additional

Published
2024
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3. Bacteriophage-driven emergence and expansion of Staphylococcus aureus in rodent populations.

Author

Yebra, Gonzalo, Mrochen, Daniel, Fischer, Stefan, Pfaff, Florian, Ulrich, Rainer G., Pritchett-Corning, Kathleen, Holtfreter, Silva, and Fitzgerald, J. Ross

Subjects
RODENT populations, BACTERIOPHAGES, MOBILE genetic elements, STAPHYLOCOCCUS aureus, LABORATORY mice, LABORATORY rodents
Abstract

Human activities such as agriculturalization and domestication have led to the emergence of many new pathogens via host-switching events between humans, domesticated and wild animals. Staphylococcus aureus is a multi-host opportunistic pathogen with a global healthcare and economic burden. Recently, it was discovered that laboratory and wild rodents can be colonised and infected with S. aureus, but the origins and zoonotic potential of rodent S. aureus is unknown. In order to trace their evolutionary history, we employed a dataset of 1249 S. aureus genome sequences including 393 of isolates from rodents and other small mammals (including newly determined sequences for 305 isolates from 7 countries). Among laboratory mouse populations, we identified multiple widespread rodent-specific S. aureus clones that likely originated in humans. Phylogeographic analysis of the most common murine lineage CC88 suggests that it emerged in the 1980s in laboratory mouse facilities most likely in North America, from where it spread to institutions around the world, via the distribution of mice for research. In contrast, wild rodents (mice, voles, squirrels) were colonized with a unique complement of S. aureus lineages that are widely disseminated across Europe. In order to investigate the molecular basis for S. aureus adaptation to rodent hosts, genome-wide association analysis was carried out revealing a unique complement of bacteriophages associated with a rodent host ecology. Of note, we identified novel prophages and pathogenicity islands in rodent-derived S. aureus that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes promoting survival in new host-species. Author summary: New pathogens typically emerge after host-switching events, threatening public health and food security. Here we used an evolutionary genomic approach to reveal the origins of Staphylococcus aureus in laboratory and wild rodent populations. S. aureus in laboratory rodents appears to have originated in humans and following host jump events has spread around the world via the distribution of mice for research purposes. Distinct clones of S. aureus widely distributed around Europe are associated with wild rodent populations. We found unique types of prophages in rodent S. aureus that have played a central role in their emergence and expansion including some with genes encoding putative virulence factors. In particular, we identified novel prophages and pathogenicity islands that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Taken together, our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes acquired via mobile genetic elements. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Ectopic Expression of C-Type Lectin Mincle Renders Mice Susceptible to Staphylococcal Pneumonia.

Author

Hollwedel, Femke D, Maus, Regina, Stolper, Jennifer, Iwai, Satoru, Kasai, Hayato, Holtfreter, Silva, Pich, Andreas, Neubert, Lavinia, Welte, Tobias, Yamasaki, Sho, and Maus, Ulrich A

Subjects
STAPHYLOCOCCUS aureus, GLYCOLIPIDS, LUNGS, PROTEOMICS, PHAGOCYTES, LECTINS
Abstract

Staphylococcus aureus is a prevalent pathogen in pneumonia and harbors glycolipids, which may serve as molecular patterns in Mincle (macrophage-inducible C-type lectin)–dependent pathogen recognition. We examined the role of Mincle in lung defense against S aureus in wild-type (WT), Mincle knockout (KO), and Mincle transgenic (tg) mice. Two glycolipids, glucosyl-diacylglycerol (Glc-DAG) and diglucosyl-diacylglycerol (Glc2-DAG), were purified, of which only Glc-DAG triggered Mincle reporter cell activation and professional phagocyte responses. Proteomic profiling revealed that Glc2-DAG blocked Glc-DAG–induced cytokine responses, thereby acting as inhibitor of Glc-DAG/Mincle signaling. WT mice responded to S aureus with a similar lung pathology as Mincle KO mice, most likely due to Glc2-DAG–dependent inhibition of Glc-DAG/Mincle signaling. In contrast, ectopic Mincle expression caused severe lung pathology in S aureus –infected mice, characterized by bacterial outgrowth and fatal pneumonia. Collectively, Glc2-DAG inhibits Glc-DAG/Mincle–dependent responses in WT mice, whereas sustained Mincle expression overrides Glc2-DAG–mediated inhibitory effects, conferring increased host susceptibility to S aureus. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Toxin exposure and HLA alleles determine serum antibody binding to toxic shock syndrome toxin 1 (TSST-1) of Staphylococcus aureus

Author

Weiss, Stefan, primary, Holtfreter, Silva, additional, Meyer, Tanja C., additional, Schmiedeke, Frieder, additional, Cammann, Clemens, additional, Dörr, Marcus, additional, Felix, Stephan B., additional, Grabe, Hans J., additional, Homuth, Georg, additional, Kohler, Christian, additional, Mahncke, Cedric, additional, Michalik, Stephan, additional, Nauck, Matthias, additional, Friedrich, Nele, additional, Samietz, Stefanie, additional, Völzke, Henry, additional, Völker, Uwe, additional, and Bröker, Barbara M., additional

Published
2023
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9. Wild rodents and shrews are natural hosts of Staphylococcus aureus

Author

Mrochen, Daniel M., Schulz, Daniel, Fischer, Stefan, Jeske, Kathrin, El Gohary, Heba, Reil, Daniela, Imholt, Christian, Trübe, Patricia, Suchomel, Josef, Tricaud, Emilie, Jacob, Jens, Heroldová, Marta, Bröker, Barbara M., Strommenger, Birgit, Walther, Birgit, Ulrich, Rainer G., and Holtfreter, Silva

Published
2018
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12. Correction to: Susceptibility of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) to chlorhexidine digluconate, octenidine dihydrochloride, polyhexanide, PVP-iodine and triclosan in comparison to hospital-acquired MRSA (HA-MRSA) and community-aquired MRSA (CA-MRSA): a standardized comparison

Author

Dittmann, Kathleen, Schmidt, Thomas, Müller, Gerald, Cuny, Christiane, Holtfreter, Silva, Troitzsch, Daniel, Pfaff, Peter, and Hübner, Nils-Olaf

Published
2019
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13. The Greifswald Post COVID Rehabilitation Study and Research (PoCoRe)–Study Design, Characteristics and Evaluation Tools

Author

Steinmetz, Anke, primary, Bahlmann, Susanne, additional, Bergelt, Corinna, additional, Bröker, Barbara M., additional, Ewert, Ralf, additional, Felix, Stephan B., additional, Flöel, Agnes, additional, Fleischmann, Robert, additional, Hoffmann, Wolfgang, additional, Holtfreter, Silva, additional, Nauck, Matthias, additional, Riemann, Katja, additional, Scheer, Christian, additional, Stahl, Dana, additional, Vogelgesang, Antje, additional, Völker, Uwe, additional, Wiesmann, Ulrich, additional, Klinger-König, Johanna, additional, Walk, René, additional, Grabe, Hans J., additional, Gross, Stefan, additional, Lehnert, Kristin, additional, Fielitz, Jens, additional, and Dörr, Marcus, additional

Published
2023
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14. Susceptibility of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) to chlorhexidine digluconate, octenidine dihydrochloride, polyhexanide, PVP-iodine and triclosan in comparison to hospital-acquired MRSA (HA-MRSA) and community-aquired MRSA (CA-MRSA): a standardized comparison

Author

Dittmann, Kathleen, Schmidt, Thomas, Müller, Gerald, Cuny, Christiane, Holtfreter, Silva, Troitzsch, Daniel, Pfaff, Peter, and Hübner, Nils-Olaf

Published
2019
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16. Cohort Profile Update: The Study of Health in Pomerania (SHIP)

Author

Völzke, Henry, primary, Schössow, Janka, additional, Schmidt, Carsten Oliver, additional, Jürgens, Clemens, additional, Richter, Adrian, additional, Werner, André, additional, Werner, Nicole, additional, Radke, Dörte, additional, Teumer, Alexander, additional, Ittermann, Till, additional, Schauer, Birgit, additional, Henck, Vivien, additional, Friedrich, Nele, additional, Hannemann, Anke, additional, Winter, Theresa, additional, Nauck, Matthias, additional, Dörr, Marcus, additional, Bahls, Martin, additional, Felix, Stephan B, additional, Stubbe, Beate, additional, Ewert, Ralf, additional, Frost, Fabian, additional, Lerch, Markus M, additional, Grabe, Hans J, additional, Bülow, Robin, additional, Otto, Markus, additional, Hosten, Norbert, additional, Rathmann, Wolfgang, additional, Schminke, Ulf, additional, Großjohann, Rico, additional, Tost, Frank, additional, Homuth, Georg, additional, Völker, Uwe, additional, Weiss, Stefan, additional, Holtfreter, Silva, additional, Bröker, Barbara M, additional, Zimmermann, Kathrin, additional, Kaderali, Lars, additional, Winnefeld, Marc, additional, Kristof, Boris, additional, Berger, Klaus, additional, Samietz, Stefanie, additional, Schwahn, Christian, additional, Holtfreter, Birte, additional, Biffar, Reiner, additional, Kindler, Stefan, additional, Wittfeld, Katharina, additional, Hoffmann, Wolfgang, additional, and Kocher, Thomas, additional

Published
2022
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21. Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2

Author

Thiele, Thomas, primary, Ulm, Lena, additional, Holtfreter, Silva, additional, Schönborn, Linda, additional, Kuhn, Sven Olaf, additional, Scheer, Christian, additional, Warkentin, Theodore E., additional, Bröker, Barbara M., additional, Becker, Karsten, additional, Aurich, Konstanze, additional, Selleng, Kathleen, additional, Hübner, Nils-Olaf, additional, and Greinacher, Andreas, additional

Published
2021
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22. Diversity of prophages in dominant Staphylococcus aureus clonal lineages

Author

Goerke, Christiane, Pantucek, Roman, Holtfreter, Silva, Schulte, Berit, Zink, Manuel, Grumann, Dorothee, Broker, Barbara M., Doskar, Jiri, and Wolz, Christiane

Subjects
Staphylococcus aureus -- Physiological aspects, Bacteriophages -- Genetic aspects, Bacteria, Pathogenic -- Physiological aspects, Biological diversity -- Evaluation, Biological sciences
Abstract

Temperate bacteriophages play an important role in the pathogenicity of Staphylococcus aureus, for instance, by mediating the horizontal gene transfer of virulence factors. Here we established a classification scheme for staphylococcal prophages of the major Siphoviridae family based on integrase gene polymorphism. Seventy-one published genome sequences of staphylococcal phages were clustered into distinct integrase groups which were related to the chromosomal integration site and to the encoded virulence gene content. Analysis of three marker modules (lysogeny, tail, and lysis) for phage functional units revealed that these phages exhibit different degrees of genome mosaicism. The prevalence of prophages in a representative S. aureus strain collection consisting of 386 isolates of diverse origin was determined. By linking the phage content to dominant S. aureus clonal complexes we could show that the distribution of bacteriophages varied remarkably between lineages, indicating restriction-based barriers. A comparison of colonizing and invasive S. aureus strain populations revealed that hlb-converting phages were significantly more frequent in colonizing strains.

Published
2009

23. Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization

Author

Fernandes de Oliveira, Liliane Maria, primary, Steindorff, Marina, additional, Darisipudi, Murthy N., additional, Mrochen, Daniel M., additional, Trübe, Patricia, additional, Bröker, Barbara M., additional, Brönstrup, Mark, additional, Tegge, Werner, additional, and Holtfreter, Silva, additional

Published
2021
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25. Staphylococcus aureus Interferes with Streptococci Spatial Distribution and with Protein Expression of Species within a Polymicrobial Oral Biofilm

Author

Schnurr, Etyene, primary, Paqué, Pune N., additional, Attin, Thomas, additional, Nanni, Paolo, additional, Grossmann, Jonas, additional, Holtfreter, Silva, additional, Bröker, Barbara M., additional, Kohler, Christian, additional, Diep, Binh An, additional, Ribeiro, Apoena de Aguiar, additional, and Thurnheer, Thomas, additional

Published
2021
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26. Allergy : a new role for T cell superantigens of Staphylococcus aureus?

Author

Abdurrahman, Goran, Schmiedeke, Frieder, Bachert, Claus, Broeker, Barbara M., and Holtfreter, Silva

Subjects
MICROBIAL SUPERANTIGENS, Staphylococcus aureus, superantigens, T cell superallergen, SHOCK-SYNDROME TOXIN-1, MONOCLONAL-ANTIBODY, T cells, CLASS-II MOLECULES, IGE SENSITIZATION, chemical and pharmacologic phenomena, CHRONIC RHINOSINUSITIS, PERIPHERAL-BLOOD, allergy, sensitization, body regions, NONTOXIC MUTANT, ENTEROTOXIN-B, parasitic diseases, Medicine and Health Sciences, CRYSTAL-STRUCTURE, IgE
Abstract

Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive cytokine release. To date, 26 different SAgs have been described in the species S. aureus; they comprise the toxic shock syndrome toxin (TSST-1), as well as 25 staphylococcal enterotoxins (SEs) or enterotoxin-like proteins (SEls). SAgs can cause staphylococcal food poisoning and toxic shock syndrome and contribute to the clinical symptoms of staphylococcal infection. In addition, there is growing evidence that SAgs are involved in allergic diseases. This review provides an overview on recent epidemiological data on the involvement of S. aureus SAgs and anti-SAg-IgE in allergy, demonstrating that being sensitized to SEs-in contrast to inhalant allergens-is associated with a severe disease course in patients with chronic airway inflammation. The mechanisms by which SAgs trigger or amplify allergic immune responses, however, are not yet fully understood. Here, we discuss known and hypothetical pathways by which SAgs can drive an atopic disease.

Published
2020

28. Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses

Author

Bonifacius, Agnes, primary, Goldmann, Oliver, additional, Floess, Stefan, additional, Holtfreter, Silva, additional, Robert, Philippe A., additional, Nordengrün, Maria, additional, Kruse, Friederike, additional, Lochner, Matthias, additional, Falk, Christine S., additional, Schmitz, Ingo, additional, Bröker, Barbara M., additional, Medina, Eva, additional, and Huehn, Jochen, additional

Published
2020
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29. Molecular Epidemiology of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Wild, Captive and Laboratory Rats: Effect of Habitat on the Nasal S. aureus Population

Author

Raafat, Dina, primary, Mrochen, Daniel M., additional, Al’Sholui, Fawaz, additional, Heuser, Elisa, additional, Ryll, René, additional, Pritchett-Corning, Kathleen R., additional, Jacob, Jens, additional, Walther, Bernd, additional, Matuschka, Franz-Rainer, additional, Richter, Dania, additional, Westerhüs, Uta, additional, Pikula, Jiri, additional, van den Brandt, Jens, additional, Nicklas, Werner, additional, Monecke, Stefan, additional, Strommenger, Birgit, additional, van Alen, Sarah, additional, Becker, Karsten, additional, Ulrich, Rainer G., additional, and Holtfreter, Silva, additional

Published
2020
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33. Lack of P-glycoprotein Results in Impairment of Removal of Beta-Amyloid and Increased Intraparenchymal Cerebral Amyloid Angiopathy after Active Immunization in a Transgenic Mouse Model of Alzheimer's Disease

Author

Bruckmann, Sascha, primary, Brenn, Anja, additional, Grube, Markus, additional, Niedrig, Katharina, additional, Holtfreter, Silva, additional, von Bohlen und Halbach, Oliver, additional, Groschup, Martin, additional, Keller, Markus, additional, and Vogelgesang, Silke, additional

Published
2017
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34. Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a Systemic Immune Response—Note of Caution for In vivo Infection Experiments

Author

Schulz, Daniel, primary, Grumann, Dorothee, additional, Trübe, Patricia, additional, Pritchett-Corning, Kathleen, additional, Johnson, Sarah, additional, Reppschläger, Kevin, additional, Gumz, Janine, additional, Sundaramoorthy, Nandakumar, additional, Michalik, Stephan, additional, Berg, Sabine, additional, van den Brandt, Jens, additional, Fister, Richard, additional, Monecke, Stefan, additional, Uy, Benedict, additional, Schmidt, Frank, additional, Bröker, Barbara M., additional, Wiles, Siouxsie, additional, and Holtfreter, Silva, additional

Published
2017
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35. Natural Colonization of Laboratory Mice withStaphylococcus aureusPrimes a Systemic Immune Response

Author

Schulz, Daniel, primary, Grumann, Dorothee, additional, Trübe, Patricia, additional, Pritchett-Corning, Kathleen, additional, Johnson, Sarah, additional, Reppschläger, Kevin, additional, Gumz, Janine, additional, Sundaramoorthy, Nandakumar, additional, Michalik, Stephan, additional, Berg, Sabine, additional, van den Brandt, Jens, additional, Fister, Richard, additional, Monecke, Stefan, additional, Uy, Benedict, additional, Schmidt, Frank, additional, Bröker, Barbara M., additional, Wiles, Siouxsie, additional, and Holtfreter, Silva, additional

Published
2017
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37. Molecular Epidemiology of Staphylococcus aureus in the General Population in Northeast Germany: Results of the Study of Health in Pomerania (SHIP-TREND-0)

Author

Holtfreter, Silva, primary, Grumann, Dorothee, additional, Balau, Veronika, additional, Barwich, Annette, additional, Kolata, Julia, additional, Goehler, André, additional, Weiss, Stefan, additional, Holtfreter, Birte, additional, Bauerfeind, Stephanie S., additional, Döring, Paula, additional, Friebe, Erika, additional, Haasler, Nicole, additional, Henselin, Kristin, additional, Kühn, Katrin, additional, Nowotny, Sophie, additional, Radke, Dörte, additional, Schulz, Katrin, additional, Schulz, Sebastian R., additional, Trübe, Patricia, additional, Vu, Chi Hai, additional, Walther, Birgit, additional, Westphal, Susanne, additional, Cuny, Christiane, additional, Witte, Wolfgang, additional, Völzke, Henry, additional, Grabe, Hans Jörgen, additional, Kocher, Thomas, additional, Steinmetz, Ivo, additional, and Bröker, Barbara M., additional

Published
2016
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40. Intrazellulär persistierende Stapylococcus aureus Stämme als vorherrschendes Pathogen bei chronisch rezidivierender nicht abszedierender Tonsillitis

Author

Krause, Merit, Zautner, Andreas, Holtfreter, Silva, and Pau, Hans Wilhelm

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

In dieser prospektiven Studie wurde das Erregerspektrum bei chron. rez. Tonsillitis und ihre Lokalisation im Gewebe im Hinblick auf das Versagen der medikamentösen Therapie untersucht. ES wurde Tonsillengewebe von 130 Patienten mit chron. rez. Tonsillitis und von 124 Patienten mit PTA auf intra-[for full text, please go to the a.m. URL], 80. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie

Published
2009

41. Characterization of a Mouse-Adapted Staphylococcus aureus Strain

Author

Holtfreter, Silva, primary, Radcliff, Fiona J., additional, Grumann, Dorothee, additional, Read, Hannah, additional, Johnson, Sarah, additional, Monecke, Stefan, additional, Ritchie, Stephen, additional, Clow, Fiona, additional, Goerke, Christiane, additional, Bröker, Barbara M., additional, Fraser, John D., additional, and Wiles, Siouxsie, additional

Published
2013
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42. Subpopulations of Staphylococcus aureus Clonal Complex 121 Are Associated with Distinct Clinical Entities

Author

Kurt, Kevin, primary, Rasigade, Jean-Philippe, additional, Laurent, Frederic, additional, Goering, Richard V., additional, Žemličková, Helena, additional, Machova, Ivana, additional, Struelens, Marc J., additional, Zautner, Andreas E., additional, Holtfreter, Silva, additional, Bröker, Barbara, additional, Ritchie, Stephen, additional, Reaksmey, Sin, additional, Limmathurotsakul, Direk, additional, Peacock, Sharon J., additional, Cuny, Christiane, additional, Layer, Franziska, additional, Witte, Wolfgang, additional, and Nübel, Ulrich, additional

Published
2013
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43. Distinctive patterns in the human antibody response to Staphylococcus aureus bacteremia in carriers and non‐carriers

Author

Kolata, Julia, primary, Bode, Lonneke G. M., additional, Holtfreter, Silva, additional, Steil, Leif, additional, Kusch, Harald, additional, Holtfreter, Birte, additional, Albrecht, Dirk, additional, Hecker, Michael, additional, Engelmann, Susanne, additional, van Belkum, Alex, additional, Völker, Uwe, additional, and Bröker, Barbara M., additional

Published
2011
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