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3. Implementation of a Clostridioides difficile sentinel surveillance system in Germany: First insights for 2019–2021

Author

Haase, Gerhard, Häfner, Helga, Hoffmann, Reinhard, Simon, Valeska, Stappmanns, Hannes, Hischebeth, Gunnar T.R., Büchler, Christian, Rößler, Susann, Hochauf-Stange, Kristina, Pfeffer, Klaus, MacKenzie, Colin, Kunz, Caroline, Alsalameh, Rayya, Dziobaka, Jan, le Chapot, Valérie Saout, Sanabria, Erwin, Hogardt, Michael, Komp, Johanna, Imirzalioglu, Can, Schmiedel, Judith, Pararas, Michael, Sommer, Frank, Groß, Uwe, Bohne, Wolfgang, Kekulé, Alexander S., Dagwadordsch, Urantschimeg, Löffler, Bettina, Rödel, Jürgen, Walker, Sarah Victoria, Tobys, David, Weikert-Asbeck, Simone, Hauswaldt, Susanne, Kaasch, Achim J., Zautner, Andreas E., Joß, Nadja, Siegel, Ekkehard, Kehr, Katharina, Schaumburg, Frieder, Schoeler, Sarah, Hamprecht, Axel, Hellkamp, Josef, Hagemann, Jürgen Benjamin, Kubis, Jan, Hering, Silvio, Warnke, Philipp, Abdrabou, Ahmed Mohamed Mostafa, Bischoff, Markus, Mellmann, Alexander, von Müller, Lutz, Margardt, Lena, Gärtner, Barbara C., and Berger, Fabian K.

Published
2022
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9. Quality assurance for genotyping and resistance testing of Clostridium (Clostridioides) difficile isolates - Experiences from the first inter-laboratory ring trial in four German speaking countries

Author

Schneeberg, Alexander, Egli, Adrian, Maurischat, Sven, Jazmati, Nathalie, Malecki, Monika, Nübel, Ulrich, Junker, Vera, Bettge-Weller, Gudrun, Pranada, Felix, Pranada, Arthur, Perrin, Monique, Kolbe-Busch, Susanne, MacKenzie, Colin, Groß, Uwe, Färber, Jacqueline, Gawlik, Darius, Monecke, Stefan, Seyboldt, Christian, Berger, Anja, Tuschak, Christian, Lâm, Thien-Tri, Hiergeist, Andreas, Reischl, Udo, Adam, Maja, Baumgartner, Stefanie, Mantlik, Katrin, Berger, Fabian K., Mellmann, Alexander, von Müller, Lutz, Bischoff, Markus, and Gärtner, Barbara C.

Published
2020
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14. Occurrence, resistance patterns, and management of carbapenemase-producing bacteria in war-wounded refugees from Ukraine

Author

Berger, Fabian K., primary, Schmartz, Georges P., additional, Fritz, Tobias, additional, Veith, Nils, additional, Alhussein, Farah, additional, Roth, Sophie, additional, Schneitler, Sophie, additional, Gilcher, Thomas, additional, Gärtner, Barbara C., additional, Pirpilashvili, Vakhtang, additional, Pohlemann, Tim, additional, Keller, Andreas, additional, Rehner, Jacqueline, additional, and Becker, Sören L., additional

Published
2023
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15. Aktuelle molekulare Epidemiologie und Antibiotikaresistenzen von Clostridioides difficile in Deutschland im Jahr 2022

Author

Berger, Fabian K., Mellmann, Alexander, von Müller, Lutz, and Gärtner, Barbara

Subjects
Sequenzierung, Ribotyp, ddc:610, Clostridium difficile, Antibiotic Stewardship, Ausbruch, 610 Medizin und Gesundheit
Abstract

Clostridioides (C.) difficile ist der bedeutendste bakte¬rielle Erreger infektiöser nosokomialer Diarrhöen. Wichtigster Risikofaktor für eine Erkrankung ist die Gabe von Antibiotika, die die Darmflora schädigen – insbesondere die „4C“-Antibiotika Clindamycin, Fluorchinolone, Cephalosporine und Aminopenicilline mit Betalaktamase-Inhibitoren. Das Epidemiologische Bulletin 15/2023 gibt einen Überblick über die aktuellen Entwicklungen der C. difficile-Epidemiologie und Resistenzentwicklung in Deutschland. Veränderungen der Erregerepidemiologie und das Erkennen von neuen Erreger- und Resistenzvarianten erfordern eine kontinuierliche Surveillance, die seit 2019 standardisiert in Deutschland am Nationalen Referenzzentrum für C. difficile durchgeführt wird.

Published
2023

16. Clostridioides difficile from Fecally Contaminated Environmental Sources: Resistance and Genetic Relatedness from a Molecular Epidemiological Perspective.

Author

Blau, Khald, Berger, Fabian K., Mellmann, Alexander, and Gallert, Claudia

Subjects
CLOSTRIDIOIDES difficile, CLARITHROMYCIN, WHOLE genome sequencing, LACTAMS, MICROBIAL sensitivity tests, DRUG resistance in microorganisms, MOXIFLOXACIN
Abstract

Clostridioides difficile is the most important pathogen causing antimicrobial-associated diarrhea and has recently been recognized as a cause of community-associated C. difficile infection (CA-CDI). This study aimed to characterize virulence factors, antimicrobial resistance (AMR), ribotype (RT) distribution and genetic relationship of C. difficile isolates from diverse fecally contaminated environmental sources. C. difficile isolates were recovered from different environmental samples in Northern Germany. Antimicrobial susceptibility testing was determined by E-test or disk diffusion method. Toxin genes (tcdA and tcdB), genes coding for binary toxins (cdtAB) and ribotyping were determined by PCR. Furthermore, 166 isolates were subjected to whole genome sequencing (WGS) for core genome multi-locus sequence typing (cgMLST) and extraction of AMR and virulence-encoding genes. Eighty-nine percent (148/166) of isolates were toxigenic, and 51% (76/148) were positive for cdtAB. Eighteen isolates (11%) were non-toxigenic. Thirty distinct RTs were identified. The most common RTs were RT127, RT126, RT001, RT078, and RT014. MLST identified 32 different sequence types (ST). The dominant STs were ST11, followed by ST2, ST3, and ST109. All isolates were susceptible to vancomycin and metronidazole and displayed a variable rate of resistance to moxifloxacin (14%), clarithromycin (26%) and rifampicin (2%). AMR genes, such as gyrA/B, blaCDD-1/2, aph(3′)-llla-sat-4-ant(6)-la cassette, ermB, tet(M), tet(40), and tetA/B(P), conferring resistance toward fluoroquinolone, beta-lactam, aminoglycoside, macrolide and tetracycline antimicrobials, were found in 166, 137, 29, 32, 21, 72, 17, and 9 isolates, respectively. Eleven "hypervirulent" RT078 strains were detected, and several isolates belonged to RTs (i.e., RT127, RT126, RT023, RT017, RT001, RT014, RT020, and RT106) associated with CA-CDI, indicating possible transmission between humans and environmental sources pointing out to a zoonotic potential. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Implementation of a Clostridioides difficile sentinel surveillance system in Germany: First insights for 2019–2021

Author

Abdrabou, Ahmed Mohamed Mostafa, primary, Bischoff, Markus, additional, Mellmann, Alexander, additional, von Müller, Lutz, additional, Margardt, Lena, additional, Gärtner, Barbara C., additional, Berger, Fabian K., additional, Haase, Gerhard, additional, Häfner, Helga, additional, Hoffmann, Reinhard, additional, Simon, Valeska, additional, Stappmanns, Hannes, additional, Hischebeth, Gunnar T.R., additional, Büchler, Christian, additional, Rößler, Susann, additional, Hochauf-Stange, Kristina, additional, Pfeffer, Klaus, additional, MacKenzie, Colin, additional, Kunz, Caroline, additional, Alsalameh, Rayya, additional, Dziobaka, Jan, additional, le Chapot, Valérie Saout, additional, Sanabria, Erwin, additional, Hogardt, Michael, additional, Komp, Johanna, additional, Imirzalioglu, Can, additional, Schmiedel, Judith, additional, Pararas, Michael, additional, Sommer, Frank, additional, Groß, Uwe, additional, Bohne, Wolfgang, additional, Kekulé, Alexander S., additional, Dagwadordsch, Urantschimeg, additional, Löffler, Bettina, additional, Rödel, Jürgen, additional, Walker, Sarah Victoria, additional, Tobys, David, additional, Weikert-Asbeck, Simone, additional, Hauswaldt, Susanne, additional, Kaasch, Achim J., additional, Zautner, Andreas E., additional, Joß, Nadja, additional, Siegel, Ekkehard, additional, Kehr, Katharina, additional, Schaumburg, Frieder, additional, Schoeler, Sarah, additional, Hamprecht, Axel, additional, Hellkamp, Josef, additional, Hagemann, Jürgen Benjamin, additional, Kubis, Jan, additional, Hering, Silvio, additional, and Warnke, Philipp, additional

Published
2022
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18. Molecular characterization, toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon

Author

Berger, Fabian K., Rasheed, Sari S., Araj, George F., Mahfouz, Rami, Rimmani, Hussein H., Karaoui, Walid R., Sharara, Ala I., Dbaibo, Ghassan, Becker, Sören L., Von Müller, Lutz, Bischoff, Markus, Matar, Ghassan M., and Gärtner, Barbara

Subjects
Middle East, BI/NAP1/027, Epidemiology, Prevalence, Distribution, MLST
Published
2022
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21. Epidemiology of Clostridioides difficileInfections in Germany, 2010–2019: A Review from Four Public Databases

Author

Brestrich, Gordon, Angulo, Frederick J., Berger, Fabian K., Brösamle, Christian, Hagel, Stefan, Leischker, Andreas, Lübbert, Christoph, Maechler, Friederike, Merbecks, Sophie-Susann, Minarovic, Nadia, Moïsi, Jennifer C., von Müller, Lutz, Reuken, Phillip A., Weinke, Thomas, Yu, Holly, and Mellmann, Alexander

Abstract

Introduction: Clostridioides difficileinfection (CDI) is a recognized global threat especially for vulnerable populations. It is of particular concern to healthcare providers as it is found in both hospital and community settings, with severe courses, frequent recurrence, high mortality and substantial financial impact on the healthcare system. The CDI burden in Germany has been described and compared by analysing data from four different public databases. Methods: Data on hospital burden of CDI have been extracted, compared, and discussed from four public databases for the years 2010–2019. Hospital days due to CDI were compared to established vaccine preventable diseases, such as influenza and herpes zoster, and also to CDI hospitalisations in the United States (US). Results: All four databases reported comparable incidences and trends. Beginning in 2010, population-based hospitalised CDI incidence increased to a peak of > 137/100,000 in 2013. Then, incidence declined to 81/100,000 in 2019. Hospitalised patients with CDI were predominantly > 50 years of age. The population-based incidence of severe CDI was between 1.4 and 8.4/100,000 per year. Recurrence rates were between 5.9 to 6.5%. More than 1,000 CDI deaths occurred each year, with a peak of 2,666 deaths in 2015. Cumulative CDI patient days (PD) were between 204,596 and 355,466 each year, which exceeded cumulated PD for influenza and herpes zoster in most years, though year-to-year differences were observed. Finally, hospitalized CDI incidence was higher in Germany than in the US, where the disease is well recognized as a public health threat. Conclusions: All four public sources documented a decline in CDI cases since 2013, but the disease burden remains substantial and warrants continued attention as a severe public health challenge.

Published
2023
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22. Additional file 1 of Combined antibiotic stewardship and infection control measures to contain the spread of linezolid-resistant Staphylococcus epidermidis in an intensive care unit

Author

Papan, Cihan, Schröder, Matthias, Hoffmann, Mathias, Knoll, Heike, Last, Katharina, Albrecht, Frederic, Geisel, Jürgen, Fink, Tobias, Gärtner, Barbara C., Mellmann, Alexander, Volk, Thomas, Berger, Fabian K., and Becker, Sören L.

Abstract

Additional file 1: Figure S1. Pocket card on the use of antibiotics with Gram-positive coverage, provided during the antimicrobial stewardship intervention on an intensive care unit in southwest Germany, 2018–2020.

Published
2021
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23. Additional file 3 of Combined antibiotic stewardship and infection control measures to contain the spread of linezolid-resistant Staphylococcus epidermidis in an intensive care unit

Author

Papan, Cihan, Schröder, Matthias, Hoffmann, Mathias, Knoll, Heike, Last, Katharina, Albrecht, Frederic, Geisel, Jürgen, Fink, Tobias, Gärtner, Barbara C., Mellmann, Alexander, Volk, Thomas, Berger, Fabian K., and Becker, Sören L.

Abstract

Additional file 3: Table S2. Expenses for the three antibiotics studied during the investigation of an outbreak by linezolid-resistant Staphylococcus epidermidis on an intensive care unit in Germany, for 2018 and 2019 each, and the calculated differences.

Published
2021
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27. Risk Factors for Primary Clostridium difficile Infection; Results From the Observational Study of Risk Factors for Clostridium difficile Infection in Hospitalized Patients With Infective Diarrhea (ORCHID)

Author

Davies, Kerrie, primary, Lawrence, Jody, additional, Berry, Claire, additional, Davis, Georgina, additional, Yu, Holly, additional, Cai, Bing, additional, Gonzalez, Elisa, additional, Prantner, Ida, additional, Kurcz, Andrea, additional, Macovei, Ioana, additional, Pituch, Hanna, additional, Nováková, Elena, additional, Nyč, Otakar, additional, Gärtner, Barbara, additional, Berger, Fabian K., additional, Oleastro, Monica, additional, Cornely, Oliver A., additional, Vehreschild, Maria J. G. T., additional, Pedneault, Louise, additional, and Wilcox, Mark, additional

Published
2020
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28. N-Aryl-3-mercaptosuccinimides as Antivirulence Agents Targeting Pseudomonas aeruginosa Elastase and Clostridium Collagenases

Author

Konstantinović, Jelena, primary, Yahiaoui, Samir, additional, Alhayek, Alaa, additional, Haupenthal, Jörg, additional, Schönauer, Esther, additional, Andreas, Anastasia, additional, Kany, Andreas M., additional, Müller, Rolf, additional, Koehnke, Jesko, additional, Berger, Fabian K., additional, Bischoff, Markus, additional, Hartmann, Rolf W., additional, Brandstetter, Hans, additional, and Hirsch, Anna K. H., additional

Published
2020
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29. Journal of Medicinal Chemistry / N-Aryl-3-mercaptosuccinimides as Antivirulence Agents Targeting Pseudomonas aeruginosa Elastase and Clostridium Collagenases

Author

Konstantinović, Jelena, Yahiaoui, Samir, Alhayek, Alaa, Haupenthal, Jörg, Schönauer, Esther, Andreas, Anastasia, Kany, Andreas M., Müller, Rolf, Koehnke, Jesko, Berger, Fabian K., Bischoff, Markus, Hartmann, Rolf W., Brandstetter, Hans, and Hirsch, Anna K.H.

Abstract

In light of the global antimicrobial-resistance crisis, there is an urgent need for novel bacterial targets and antibiotics with novel modes of action. It has been shown that Pseudomonas aeruginosa elastase (LasB) and Clostridium histolyticum (Hathewaya histolytica) collagenase (ColH) play a significant role in the infection process and thereby represent promising antivirulence targets. Here, we report novel N-aryl-3-mercaptosuccinimide inhibitors that target both LasB and ColH, displaying potent activities in vitro and high selectivity for the bacterial over human metalloproteases. Additionally, the inhibitors demonstrate no signs of cytotoxicity against selected human cell lines and in a zebrafish embryo toxicity model. Furthermore, the most active ColH inhibitor shows a significant reduction of collagen degradation in an ex vivo pig-skin model. (VLID)5394757

Published
2020
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30. Simple Questionnaires to Improve Pooling Strategies for SARS-CoV-2 Laboratory Testing

Author

Schneitler, Sophie, Jung, Philipp, Bub, Florian, Alhussein, Farah, Benthien, Sophia, Berger, Fabian K., Berko-Gottel, Barbara, Eisenbeis, Janina, Hahn, Daphne, Halfmann, Alexander, Last, Katharina, Linxweiler, Maximilian, Lohse, Stefan, Papan, Cihan, Pfuhl, Thorsten, Rissland, Jurgen, Roth, Sophie, Schlotthauer, Uwe, Utzinger, Jurg, Smola, Sigrun, Gartner, Barbara C., Becker, Soren L., Schneitler, Sophie, Jung, Philipp, Bub, Florian, Alhussein, Farah, Benthien, Sophia, Berger, Fabian K., Berko-Gottel, Barbara, Eisenbeis, Janina, Hahn, Daphne, Halfmann, Alexander, Last, Katharina, Linxweiler, Maximilian, Lohse, Stefan, Papan, Cihan, Pfuhl, Thorsten, Rissland, Jurgen, Roth, Sophie, Schlotthauer, Uwe, Utzinger, Jurg, Smola, Sigrun, Gartner, Barbara C., and Becker, Soren L.

Abstract

Background: Liberal PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to contain the coronavirus disease 2019 (COVID-19) pandemic. Combined multi-sample testing in pools instead of single tests might enhance laboratory capacity and reduce costs, especially in low- and middle-income countries. Objective: The purpose of our study was to assess the value of a simple questionnaire to guide and further improve pooling strategies for SARS-CoV-2 laboratory testing. Methods: Pharyngeal swabs for SARS-CoV-2 testing were obtained from healthcare and police staff, hospital inpatients, and nursing home residents in the southwestern part of Germany. We designed a simple questionnaire, which included questions pertaining to a suggestive clinical symptomatology, recent travel history, and contact with confirmed cases to stratify an individual's pre-test probability of having contracted COVID-19. The questionnaire was adapted repeatedly in face of the unfolding pandemic in response to the evolving epidemiology and observed clinical symptomatology. Based on the response patterns, samples were either tested individually or in multi-sample pools. We compared the pool positivity rate and the number of total PCR tests required to obtain individual results between this questionnaire-based pooling strategy and randomly assembled pools. Findings: Between March 11 and July 5, 2020, we processed 25,978 samples using random pooling (n = 6,012; 23.1%) or questionnaire-based pooling (n = 19,966; 76.9%). The overall prevalence of SARSCoV-2 was 0.9% (n = 238). Pool positivity (14.6% vs. 1.2%) and individual SARS-CoV-2 prevalence (3.4% vs. 0.1%) were higher in the random pooling group than in the questionnaire group. The average number of PCR tests needed to obtain the individual result for one participant was 0.27 tests in the random pooling group, as compared to 0.09 in the questionnaire-based pooling group, leading to a laboratory capacity increase of 73% and 9

Published
2020

31. Risk Factors for PrimaryClostridium difficileInfection; Results From the Observational Study of Risk Factors forClostridium difficileInfection in Hospitalized Patients With Infective Diarrhea (ORCHID)

Author

Davies, Kerrie, Lawrence, Jody, Berry, Claire, Davis, Georgina, Yu, Holly, Cai, Bing, Gonzalez, Elisa, Prantner, Ida, Kurcz, Andrea, Macovei, Ioana, Pituch, Hanna, Novakova, Elena, Nyc, Otakar, Gaertner, Barbara, Berger, Fabian K., Oleastro, Monica, Cornely, Oliver A., Vehreschild, Maria J. G. T., Pedneault, Louise, Wilcox, Mark, Davies, Kerrie, Lawrence, Jody, Berry, Claire, Davis, Georgina, Yu, Holly, Cai, Bing, Gonzalez, Elisa, Prantner, Ida, Kurcz, Andrea, Macovei, Ioana, Pituch, Hanna, Novakova, Elena, Nyc, Otakar, Gaertner, Barbara, Berger, Fabian K., Oleastro, Monica, Cornely, Oliver A., Vehreschild, Maria J. G. T., Pedneault, Louise, and Wilcox, Mark

Abstract

Background:There are inconsistent data on the risk factors forClostridium difficileinfection (CDI) in the literature. Aims:To use twoC. difficileinfection (CDI) case-control study groups to compare risk factors in hospitalized patients with diarrhea across different countries. Methods:A multi-center group of CDI cases/controls were identified by standardized testing from seven countries from the prior EUropean, multi-center, prospective bi-annual point prevalence study ofCLostridium difficileInfection in hospitalized patients with Diarrhea (EUCLID). A second group of CDI cases/controls was identified from a single center in Germany [parallel study site (PSS)]. Data were extracted from the medical notes to assess CDI risk factors. Univariate analyses and multivariate logistic regression models were used to identify and compare risk factors between the two groups. Results:There were 253 and 158 cases and 921 and 584 controls in the PSS and EUCLID groups, respectively. Significant variables from univariate analyses in both groups were age >= 65, number of antibiotics (OR 1.2 for each additional antibiotic) and prior hospital admission (allp< 0.001). Congestive heart failure, diabetes, admission from assisted living or Emergency Department, proton pump inhibitors, and chronic renal disease were significant in PSS (allp< 0.05) but not EUCLID. Dementia and admitted with other bacterial diseases were significant in EUCLID (p< 0.05) but not PSS. Following multivariate analyses, age >= 65, number of antibiotics and prior hospital admission were consistently identified as CDI risk factors in each individual group and combined datasets. Conclusion:Our results show that the same CDI risk factors were identified across datasets. These were age >= 65 years, antibiotic use and prior hospital admission. Importantly, the odds of developing CDI increases with each extra antibiotic prescribed.

Published
2020

32. Proteotyping of Clostridioides difficile as Alternate Typing Method to Ribotyping Is Able to Distinguish the Ribotypes RT027 and RT176 From Other Ribotypes

Author

Emele, Matthias F., Joppe, Felix M., Riedel, Thomas, Overmann, Jörg, Rupnik, Maja, Cooper, Paul, Kusumawati, R. Lia, Berger, Fabian K., Laukien, Friederike, Zimmermann, Ortrud, Bohne, Wolfgang, Groß, Uwe, Bader, Oliver, and Zautner, Andreas E.

Subjects
MALDI-TOF MS, Clostridioides difficile, Clostridium difficile, below species differentiation, proteotyping
Abstract

Clostridioides difficile, a Gram-positive spore-forming bacterium, is the leading cause of nosocomial diarrhea worldwide and therefore a substantial burden to the healthcare system. During the past decade, hypervirulent PCR-ribotypes (RT) e.g., RT027 or RT176 emerged rapidly all over the world, associated with both, increased severity and mortality rates. It is thus of great importance to identify epidemic strains such as RT027 and RT176 as fast as possible. While commonly used diagnostic methods, e.g., multilocus sequence typing (MLST) or PCR-ribotyping, are time-consuming, proteotyping offers a fast, inexpensive, and reliable alternative solution. In this study, we established a MALDI-TOF-based typing scheme for C. difficile. A total of 109 ribotyped strains representative for five MLST clades were analyzed by MALDI-TOF. MLST, based on whole genome sequences, and PCR-ribotyping were used as reference methods. Isoforms of MS-detectable biomarkers, typically ribosomal proteins, were related with the deduced amino acid sequences and added to the C. difficile proteotyping scheme. In total, we were able to associate nine biomarkers with their encoding genes and include them in our proteotyping scheme. The discriminatory capacity of the C. difficile proteotyping scheme was mainly based on isoforms of L28-M (2 main isoforms), L35-M (4 main isoforms), and S20-M (2 main isoforms) giving rise to at least 16 proteotyping-derived types. In our test population, five of these 16 proteotyping-derived types were detected. These five proteotyping-derived types did not correspond exactly to the included five MLST-based C. difficile clades, nevertheless the subtyping depth of both methods was equivalent. Most importantly, proteotyping-derived clade B contained only isolates of the hypervirulent RT027 and RT176. Proteotyping is a stable and easy-to-perform intraspecies typing method and a promising alternative to currently used molecular techniques. It is possible to distinguish the group of RT027 and RT176 isolates from non-RT027/non-RT176 isolates using proteotyping, providing a valuable diagnostic tool. Open-Access-Publikationsfonds 2019 peerReviewed

Published
2019

33. Quality assurance for genotyping and resistance testing of Clostridium (Clostridioides) difficile isolates - Experiences from the first inter-laboratory ring trial in four German speaking countries

Author

Berger, Fabian K., primary, Mellmann, Alexander, additional, von Müller, Lutz, additional, Bischoff, Markus, additional, Gärtner, Barbara C., additional, Schneeberg, Alexander, additional, Egli, Adrian, additional, Maurischat, Sven, additional, Jazmati, Nathalie, additional, Malecki, Monika, additional, Nübel, Ulrich, additional, Junker, Vera, additional, Bettge-Weller, Gudrun, additional, Pranada, Felix, additional, Pranada, Arthur, additional, Perrin, Monique, additional, Kolbe-Busch, Susanne, additional, MacKenzie, Colin, additional, Groß, Uwe, additional, Färber, Jacqueline, additional, Gawlik, Darius, additional, Monecke, Stefan, additional, Seyboldt, Christian, additional, Berger, Anja, additional, Tuschak, Christian, additional, Lâm, Thien-Tri, additional, Hiergeist, Andreas, additional, Reischl, Udo, additional, Adam, Maja, additional, Baumgartner, Stefanie, additional, and Mantlik, Katrin, additional

Published
2020
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34. Simple Questionnaires to Improve Pooling Strategies for SARS-CoV-2 Laboratory Testing

Author

Schneitler, Sophie, primary, Jung, Philipp, additional, Bub, Florian, additional, Alhussein, Farah, additional, Benthien, Sophia, additional, Berger, Fabian K., additional, Berkó-Göttel, Barbara, additional, Eisenbeis, Janina, additional, Hahn, Daphne, additional, Halfmann, Alexander, additional, Last, Katharina, additional, Linxweiler, Maximilian, additional, Lohse, Stefan, additional, Papan, Cihan, additional, Pfuhl, Thorsten, additional, Rissland, Jürgen, additional, Roth, Sophie, additional, Schlotthauer, Uwe, additional, Utzinger, Jürg, additional, Smola, Sigrun, additional, Gärtner, Barbara C., additional, and Becker, Sören L., additional

Published
2020
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36. Proteotyping of Clostridioides difficile as Alternate Typing Method to Ribotyping Is Able to Distinguish the Ribotypes RT027 and RT176 From Other Ribotypes

Author

Emele, Matthias F., primary, Joppe, Felix M., additional, Riedel, Thomas, additional, Overmann, Jörg, additional, Rupnik, Maja, additional, Cooper, Paul, additional, Kusumawati, R. Lia, additional, Berger, Fabian K., additional, Laukien, Friederike, additional, Zimmermann, Ortrud, additional, Bohne, Wolfgang, additional, Groß, Uwe, additional, Bader, Oliver, additional, and Zautner, Andreas E., additional

Published
2019
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39. N-Aryl-3-mercaptosuccinimides as Antivirulence Agents Targeting Pseudomonas aeruginosaElastase and ClostridiumCollagenases

Author

Konstantinović, Jelena, Yahiaoui, Samir, Alhayek, Alaa, Haupenthal, Jörg, Schönauer, Esther, Andreas, Anastasia, Kany, Andreas M., Müller, Rolf, Koehnke, Jesko, Berger, Fabian K., Bischoff, Markus, Hartmann, Rolf W., Brandstetter, Hans, and Hirsch, Anna K. H.

Abstract

In light of the global antimicrobial-resistance crisis, there is an urgent need for novel bacterial targets and antibiotics with novel modes of action. It has been shown that Pseudomonas aeruginosaelastase (LasB) and Clostridium histolyticum(Hathewaya histolytica) collagenase (ColH) play a significant role in the infection process and thereby represent promising antivirulence targets. Here, we report novel N-aryl-3-mercaptosuccinimide inhibitors that target both LasB and ColH, displaying potent activities in vitroand high selectivity for the bacterial over human metalloproteases. Additionally, the inhibitors demonstrate no signs of cytotoxicity against selected human cell lines and in a zebrafish embryo toxicity model. Furthermore, the most active ColH inhibitor shows a significant reduction of collagen degradation in an ex vivopig-skin model.

Published
2020
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