Sabine Gröbner's research while affiliated with University of Tuebingen and other places
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Publications (23)
Migration of dendritic cells (DCs) plays an important role in T-cell-mediated adaptive immune responses. Lipopolysaccharide (LPS) sensed by Toll-like receptor 4 (TLR4) serves as a signal for DC migration. We analyzed LPS-induced DC volume changes preceding the directed movement towards chemoattractants. Treatment with LPS resulted in rapid, prolong...
We report the emergence of a multidrug-resistant Haemophilus influenzae strain in a patient with common variable immunodeficiency suffering from recurrent bronchopneumonia caused by H. influenzae. After the patient had received several antibiotic therapies, a strain was isolated showing resistance to ampicillin, ampicillin/sulbactam, cefazolin, cef...
Extended-spectrum β-lactamase (ESBL)-producing organisms are spreading worldwide in hospital and community settings.
A total of 328 unduplicated ESBL-producing Enterobacteriaceae isolated in 2008 and 2009 at the University Hospital of Tübingen were analysed retrospectively.
Escherichia coli (n = 253) and Klebsiella spp. (n = 46) were the most frequ...
While flagella-independent motility has long been described in representatives of the genus Acinetobacter, the mechanism of motility remains ambiguous. Acinetobacter baumannii, a nosocomial pathogen appearing increasingly multidrug-resistant, may profit from motility during infection or while persisting in the hospital environment. However, data on...
Small-colony variants (SCVs) of bacteria are slow-growing subpopulations which can cause latent or recurrent infections due to better intracellular survival compared to their wild-type counterparts. Atypical colony morphology and altered biochemical profile may lead to failure in identification of SCV strains. We here report for the first time the...
The prevalence of infections with enterococci is increasing worldwide. However, little is known about the mechanisms which enable these opportunistic pathogens to cause infections of their host. Here we demonstrate that Enterococcus faecium in the presence of lysozyme induces necrosis in human and mouse cells after 4 h indicated by disrupted cellul...
Enterococci are commensal organisms in the alimentary tract. However, they can cause a variety of life-threatening infections, especially in nosocomial settings. We hypothesized that induction of cell death might enable these facultative pathogenic bacteria to evade the innate immune response and to cause infections of their host. We demonstrate th...
The spread of Gram-negative bacteria with plasmid-borne extended-spectrum beta-lactamases (ESBLs) has become a worldwide problem. This study analysed a total of 366 ESBL-producing Enterobacteriaceae strains isolated from non-selected patient specimens at the university hospital of Tübingen in the period January 2003 to December 2007. Although the o...
To improve the clinical outcome of Staphylococcus aureus septicemia, the early selection of appropriate antibiotic treatment is crucial. Molecular diagnostics represents an attractive
approach for the rapid identification of S. aureus and the determination of its methicillin (meticillin) resistance. In direct comparison to other molecular assays (s...
Ein 64-jähriger bisher gesunder Patient erkrankt im Januar 2001 an einer starken Erkältung. Trotz der Erkältung geht er in
der Folgezeit seiner schweren körperlichen Arbeit weiterhin nach. In den folgenden Monaten hat er aber mehrere Rezidive zunehmenden
Schweregrades. Schließlich muss er im Juli deswegen sogar seinen Baubetrieb aufgeben. Die progr...
Yersinia enterocolitica (Ye) disrupts the ability of dendritic cells (DC) to prime CD4+ T cells suggesting that Ye may subvert uptake and/or processing of soluble antigens (Ag). To investigate this Ye-infected DC were loaded with fluorescently labelled ovalbumins as markers for Ag uptake and processing, and analysed by flow cytometry, fluorometry a...
Yersinia outer protein P (YopP) induces cell death in macrophages and dendritic cells (DC). In DC this YopP-dependent cell death coincides with the inhibition of nuclear factor-kappa B (NF-kappaB) activation. However, as shown by measurement of propidium iodide uptake via disrupted cellular membranes, the preincubation of DC with several NF-kappaB...
Ralstonia mannitolilytica is a non-fermentative, gram-negative bacterium isolated infrequently from clinical samples. However, within a period of 11 weeks five inpatients of the tertiary care hospital of the University of Tübingen developed clinical signs of infection and R. mannitolilytica was cultivated from blood samples of all patients suggesti...
Yersinia outer protein P (YopP) is injected by Y. enterocolitica into host cells thereby inducing apoptotic and necrosis-like cell death in dendritic cells (DC). Here we show the pathways involved in DC death caused by the catalytic activity of YopP. Infection with Yersinia
enterocolitica, translocating catalytically active YopP into DC, triggered...
For the rapid detection of methicillin-resistant staphylococci directly from blood cultures containing gram-positive cocci in clusters, we implemented a real-time (LightCycler) polymerase chain reaction (PCR) specific for the Staphylococcus aureus nuc gene encoding nuclease and the mecA gene encoding methicillin resistance. For the 475 positive blo...
Through Yersinia outer proteins (Yops) Yersinia disrupt the actin cytoskeleton of epithelial cells and macrophages, and this leads to a decreased capability of these cells to internalize bacteria. We examined the effects of different Yops of Y. enterocolitica serotype O8 on the cytoskeleton and phagocytic capacity of murine dendritic cells (DCs). D...
This report describes the isolation of Aeromonas veronii biovar sobria as the causative enteropathogen of diarrhoea in an oncological patient after failure of detection of other infectious agents. The case points out the severe and long course of the infection, the diagnostic dilemma, and the prompt recovery after antibiotic treatment.
In an initial period (≤4 h) Toll-like receptor 4 (TLR4) signaling is required for Yersinia enterocolitica YopP-induced dendritic cell (DC) death. Later (>4 h), DC die independent of TLR4 signaling. In TLR4-deficient DC caspase
8 cleavage is delayed, indicating that TLR4 signaling accelerates caspase 8 activation, leading to DC death.
Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica that is injected into the cytosol of host cells where it targets MAP kinase kinases (MKKs) and inhibitor of kappaB kinase (IKK)-beta resulting in inhibition of cytokine production as well as induction of apoptosis in murine macrophages and dendritic cells (DC). Here we...
Yersinia enterocolitica evades innate immunity by expression of a variety of pathogenicity factors. Therefore, adaptive immunity including CD4+ T cells plays an important role in defense against Y. enterocolitica. We investigated whether Y. enterocolitica might target dendritic cells (DC) involved in adaptive T-cell responses. For this purpose, mur...
Outbreaks of Acinetobacter baumannii demonstrating multiple antibiotic resistance, including meropenem resistance, have been described as severe therapeutic problems. Here we describe a monoclonal outbreak of infection and colonization with multidrug-resistant A. baumannii over a two-month period. Resistance to meropenem was mediated by expression...
Citations
... This resistance is not fully understood, but thought to be partially due to hyper-mucoviscosity as a result of increased polysaccharides expressed on the Klebsiella surface and secreted into the extracellular environment [87,88]. However, in immunocompetent patients, the presence of LPS and interaction between LPS and TLR-4 signals initiates dendritic cell migration and ultimately T cell activation after antigen presentation [89]. ...
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... Accordingly, ampicillin-resistant H. influenzae was added to the WHO priority pathogen list for research and development of new and effective antibiotics in 2017 (WHO, 2017). The situation is further complicated by the dissemination of multidrug-resistant (MDR) H. influenzae with acquired resistance to the most suitable non-beta-lactam agents such as trimethoprim-sulfamethoxazole, tetracyclines, quinolones, chloramphenicol, and/or macrolides (Pfeifer et al., 2013;Kuo et al., 2014;Skaare et al., 2014;Seyama et al., 2017;Hegstad et al., 2020). ...
... The prevalence rose from 0.3% in 1996 to 6.6% in 2006 and 7.4% in 2007 (Lehner et al., 2009). In Southwestern Germany, the rate increased from 2.1% in 2008 to 2.4% in 2009 (Wienke et al., 2012). Between 2008 and 2012, ARS reported a rise in resistance of ESBL KP in outpatients from 2.7% in 2008 to 6.6% in 2012 . ...
... Surface-associated motility is a kind of movement that is appendage-independent and is unique to certain A. baumannii clinical isolates (Corral et al. 2020). This type of motility corresponds to the formation of the outer membrane, lipooligosaccharide, 1,3-diaminopropane (1,3-DAP), metabolism-related proteins, and proteins from at least five of the six recognized superfamilies of efflux pumps (Blaschke et al. 2021;McQueary et al. 2012;Pérez-Varela et al. 2019;Skiebe et al. 2012). Even though A. baumannii produces a number of different virulence factors, the motility-associated proteins that have already been discussed are also responsible for the virulence function. ...
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... Furthermore, co-treatment of cells with the caspase inhibitor Z-VAD-FMK did not improve the NF-κB activation levels (supplementary Figure S2C), indicating that the E. faecium SF68 lysates were not involved in activation of apoptosis, as previously reported for other E. faecium and E. faecalis isolates. [31][32][33][34] Finally, it has previously been reported that E. faecium and Streptococcus spp. isolates produce cytotoxic levels of hydrogen peroxide leading to an oxidative stressassociated death of host cells. ...
... A paper written in Japanese showed, for thymidinedependent SCVs, that both the direct transfer-formic acid MS sample preparation method, as well as the ethanol-formic acid method, yielded equivalent results [52]. Some case reports about non-staphylococcal SCVs also indicate the suitability of the MALDI-TOF MS approach [53,54]. ...
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... Furthermore, co-treatment of cells with the caspase inhibitor Z-VAD-FMK did not improve the NF-κB activation levels (supplementary Figure S2C), indicating that the E. faecium SF68 lysates were not involved in activation of apoptosis, as previously reported for other E. faecium and E. faecalis isolates. [31][32][33][34] Finally, it has previously been reported that E. faecium and Streptococcus spp. isolates produce cytotoxic levels of hydrogen peroxide leading to an oxidative stressassociated death of host cells. ...
... Total genomic DNA for PCR and whole-genome sequencing was extracted using the PureLink™ Genomic DNA Mini Kit (Thermo Fisher Scientific, Missouri, TX, USA) following the manufacturer's instruction, except that all homogenization steps were performed by pipetting. Primer pairs from prior publications were used in a previously described multiplex PCR [30] to screen all isolates for class A, class B, and class D carbapenemases [31][32][33][34][35]. PCR conditions are detailed in Supplementary Table S5. ...
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... All of these methods offer reduced time-to-initiation of optimal therapy over traditional culture methods, which require 72 to 96 hours for species identification and antimicrobial susceptibility testing to be completed [33]. Overall, multiple reports show that this strategy of using nucleic acid amplification methods works well and provides accurate results in a timely manner [15,[34][35][36][37]. However, there are several genetic variants that have arisen among S. aureus strains that can challenge the accuracy of molecular test results. ...
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... From 2002 to 2006, the rate of isolation of A. baumannii increased in university hospitals of six German federal states (Baden-Wuerttemberg, Hesse, Lower Saxony, Saxony, Schleswig-Holstein and Thuringia) from 2.1% in 2002 to 7.9% in 2006 [46] and the proportion of MDR of A. baumannii isolates raised among inpatients [46]. XDR strains resistant to all available antibiotics except colistin have been isolated from wound, skin and respiratory tract samples in an outbreak in 2003 [14]. To overcome the resistance developed against broad-spectrum antibiotics tetracycline, tigecycline a new class of antibiotics derived from tetracycline has been implemented in 2006. ...
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