Ingo B Autenrieth

University of Tuebingen, Tübingen, Baden-Württemberg, Germany

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Publications (131)657.63 Total impact

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    ABSTRACT: The human gut forms a dynamic reservoir of antibiotic resistance genes (ARGs). Treatment with antimicrobial agents has a significant impact on the intestinal resistome, and leads to enhanced horizontal transfer and selection of resistance. We have followed the development of intestinal ARGs over a six-days course of ciprofloxacin (Cp) treatment in two healthy individuals by using sequenced-based metagenomics and different ARG quantification methods. Fixed- and random-effects models were applied to determine the change in ARG abundance per defined daily dose of Cp as an expression of the respective selection pressure. Among various shifts in the composition of the intestinal resistome we found in one individual a strong positive selection for class D beta-lactamases which were partly located on a mobile genetic element. Furthermore, a trend to a negative selection has been observed with class A beta-lactamases (-2.66 hits per million sample reads/defined daily dose; p = 0.06). By 4 weeks after the end of treatment, the composition of ARGs returned toward their initial state but to a different degree in both subjects. We present here a novel analysis algorithm for the determination of antibiotic selection pressure which can be applied in clinical settings to compare therapeutic regimes regarding their effect on the intestinal resistome. This information is of critical importance for clinicians to choose antimicrobial agents with a low selective force on their patients' intestinal ARGs, likely resulting in a diminished spread of resistance and a reduced burden of hospital-acquired infections with multidrug resistant pathogens.
    Antimicrobial Agents and Chemotherapy 09/2015; DOI:10.1128/AAC.01504-15 · 4.48 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2015; 41(08). DOI:10.1055/s-0035-1555245 · 1.05 Impact Factor
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    ABSTRACT: Dendritic cells (DCs) are professional antigen-presenting cells playing a crucial role in the initiation of T-cell responses to combat infection. However, systemic bacterial infection with various pathogens leads to DC-depletion in humans and mice. The mechanisms of pathogen-induced DC-depletion remain poorly understood. Previously, we showed that mice infected with Yersinia enterocolitica (Ye) had impaired de novo DC-development, one reason for DC-depletion. Here, we extend these studies to gain insight into the molecular mechanisms of DC-depletion and the impact of different bacteria on DC-development. We show that the number of BM hematopoietic progenitors committed to the DC lineage is reduced following systemic infection with different Gram-positive and Gram-negative bacteria. This is associated with a TLR4- and IFN-γ-signaling dependent increase of committed monocyte progenitors in the BM and mature monocytes in the spleen upon Ye-infection. Adoptive transfer experiments revealed that infection-induced monopoiesis occurs at the expense of DC-development. Our data provide evidence for a general response of hematopoietic progenitors upon systemic bacterial infections to enhance monocyte production, thereby increasing the availability of innate immune cells for pathogen control, whereas impaired DC-development leads to DC-depletion, possibly driving transient immunosuppression in bacterial sepsis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 07/2015; DOI:10.1002/eji.201545530 · 4.03 Impact Factor
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    ABSTRACT: Diagnosis of Pneumocystis jirovecii pneumonia (PjP) is challenging. Therefore highly-sensitive and time-efficient new diagnostic tools are needed for early antibiotic treatment start and optimized patient outcome. We evaluated a prototype of a new molecular diagnostic tool using PCR/microarray hybridization for P. jirovecii detection in respiratory samples of hospitalized patients suffering from pneumonia. Prototype results were first compared to established routine PCR results and were set in the context of patients' immune status and clinical presentation in an overall assessment (true positive, false negative or false positive). In our study population, P. jirovecii was assayed with both detection methods in eleven patients out of 739 evaluable study patients; of these, six cases were detected only with the prototype system, two cases only with site-established PCR and three cases with both methods. From these eleven positive cases, we found that six prototype positive cases were true false positives, three prototype positive cases were confirmed as true positives and two prototype negative cases were true false negatives. Overall prevalence for P. jirovecii was low in this study population. Although more positive cases were found using the prototype system, these cases seemed not to be of any clinical significance which might have led to an antibiotic overtreatment of patients under real conditions. However, the correct detection of three positive cases within a few hours might render the prototype a valuable diagnostic tool in the future.
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    ABSTRACT: The current paradigm suggests that Yersinia entercolitica (Ye) adheres to host cells via the outer membrane proteins YadA or invasin (Inv) to facilitate injection of Yops by the type III secretion system; in this process Inv binds directly to β1 integrins of host cells while YadA may bind indirectly via extracellular matrix proteins to β1 integrins. Here we challenged this paradigm and investigated the requirements for Yop injection. We demonstrate that Inv-, but not YadA-mediated adhesion depends on β1 integrin binding and activation, and that tight adhesion is a prerequisite for Yop injection. By means of novel transgenic cell lines, shRNA approaches and RGD peptides we found that YadA, in contrast to Inv, may use a broad host cell receptor repertoire for host cell adhesion. In the absence of β1 integrins, YadA mediates Yop injection by interaction with αV integrins in cooperation with yet unknown cofactors expressed by epithelial cells, but not fibroblasts. Electron microscopic and flow chamber studies revealed that a defined intimate contact area between Ye and host cells resulting in adhesion forces resisting shear stress is required for Yop injection. Thus, the indirect binding of YadA to a broad ECM binding host cell receptor repertoire of different cell types makes YadA a versatile tool to ensure Yop injection. In conclusion, given the differential expression of the outer membrane proteins Inv and YadA in the course of Ye infection and differential expression of integrins by various host cell populations, the data demonstrate that Ye is flexibly armed to accomplish Yop injection in different host cell types, a central event in its immune evasion strategy. This article is protected by copyright. All rights reserved.
    Cellular Microbiology 02/2015; 17(8). DOI:10.1111/cmi.12429 · 4.92 Impact Factor
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    ABSTRACT: Toll-like receptor (TLR) expression in patients with inflammatory bowel disease is increased when compared with healthy controls. However, the impact of TLR signaling during inflammatory bowel disease is not fully understood. In this study, we used a murine model of acute phase inflammation in bone marrow chimeric mice to investigate in which cell type TLR2/4 signal induction is important in preventing intestinal inflammation and how intestinal dendritic cells are influenced. Mice were either fed with wild-type bacteria, able to initiate the TLR2/4 signaling cascade, or with mutant strains with impaired signal induction capacity. The induction of the TLR2/4 signal cascade in epithelial cells resulted in inflammation in bone marrow chimeric mice, whereas induction in hematopoietic cells had an opposed function. Furthermore, feeding of wild-type bacteria prevented disease; however, differing signal induction of bacteria had no effect on lamina propria dendritic cell activation. In contrast, functional TLR2/4 signals resulted in increased frequencies of CD103-expressing lamina propria and mesenteric lymph node dendritic cells, which were able to ameliorate disease. The TLR-mediated amelioration of disease, the increase in CD103-expressing cells, and the beneficial function of TLR signal induction in hematopoietic cells indicate that the increased expression of TLRs in patients with inflammatory bowel disease might result in counterregulation of the host and serve in preventing disease.
    Inflammatory Bowel Diseases 02/2015; 21(3). DOI:10.1097/MIB.0000000000000292 · 4.46 Impact Factor
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    ABSTRACT: Here we report on a long-term outbreak from 2009 to 2012 with an XDR Pseudomonas aeruginosa on two wards at a university hospital in southern Germany. Whole-genome sequencing was performed on the outbreak isolates and a core genome was constructed for molecular epidemiological analysis. We applied a time-place-sequence algorithm to improve estimation of transmission probabilities. By using conventional infection control methods we identified 49 P. aeruginosa strains, including eight environmental isolates that belonged to ST308 (by MLST) and carried the metallo-β-lactamase IMP-8. Phylogenetic analysis on the basis of a non-recombinant core genome that contained 22 outbreak-specific SNPs revealed a pattern of four dominant clades with a strong phylogeographic structure and allowed us to determine the potential temporal origin of the outbreak to July 2008, 1 year before the index case was diagnosed. Superspreaders at the root of clades exhibited a high number of probable and predicted transmissions, indicating their exceptional position in the outbreak. Our results suggest that the initial expansion of dominant sublineages was driven by a few superspreaders, while environmental contamination seemed to sustain the outbreak for a long period despite regular environmental control measures. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail:
    Journal of Antimicrobial Chemotherapy 01/2015; 70(5). DOI:10.1093/jac/dku546 · 5.31 Impact Factor
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    ABSTRACT: Background This study aimed to investigate risk factors for colonisation with extensively drug-resistant P. aeruginosa (XDR-PA) in immunocompromised patients and to build a clinical risk score (CRS) based on these results.Methods We conducted a matched case¿control study with 31 cases and 93 controls (1:3). Cases were colonised with XDR-PA during hospitalisation. Independent risk factors were determined using a three step conditional logistic regression procedure. A CRS was built with respect to the corresponding risk fraction of each risk factor, and its discriminatory power was estimated by receiver operating characteristic (ROC) analysis.ResultsThe presence of a central venous catheter (OR 7.41, P¿=¿0.0008), the presence of a urinary catheter (OR 21.04, P¿<¿0.0001), CRP¿>¿10 mg/dl (OR 7.36, P¿=¿0.0015), and ciprofloxacin administration (OR 5.53, P¿=¿0.025) were independent risk factors. The CRS exhibited a high discriminatory power, defining a high risk population with an approximately fourteen times greater risk for XDR-PA colonisation.Conclusions Unnecessary use of antibiotics, particularly ciprofloxacin should be avoided, and a high standard of infection control measures must be achieved when using medical devices. A CRS can be used for adaptation of the active screening culture policy to the local setting.
    BMC Infectious Diseases 12/2014; 14(1):650. DOI:10.1186/s12879-014-0650-9 · 2.61 Impact Factor
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    ABSTRACT: Autotransporter proteins comprise a large family of virulence factors which consist of a β-barrel translocation unit and an extracellular effector or passenger domain. The β-barrel anchors the protein to the outer membrane of Gram-negative bacteria and facilitates the transport of the passenger domain onto the cell surface. By inserting an epitope tag into the N-terminus of the passenger domain of the inverse autotransporter Intimin, we generated a mutant defective in autotransport. Using this stalled mutant we could show that (I) at the timepoint of stalling the β-barrel appears folded, (II) the stalled autotransporter is associated with BamA and SurA, (III) the stalled Intimin is decorated with large amounts of SurA, (IV) the stalled autotransporter is not degraded by periplasmic proteases, and that (V) inverse autotransporter passenger domains are translocated by a hairpin mechanism. Our results suggest a function for the BAM complex not only in insertion and folding of the β-barrel but also for passenger translocation. Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 12/2014; 290(3). DOI:10.1074/jbc.M114.604769 · 4.57 Impact Factor
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    ABSTRACT: Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods – particularly in patients with prior antibiotic treatment – and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time. Trial Registration Deutsches Register Klinischer Studien (DRKS) DRKS00005684
    PLoS ONE 11/2014; 9(11):e110566. DOI:10.1371/journal.pone.0110566 · 3.23 Impact Factor
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    ABSTRACT: Intimin and Invasin are prototypical inverse (Type Ve) autotransporters and important virulence factors of enteropathogenic Escherichia coli and Yersinia spp., respectively. In addition to a C-terminal extracellular domain and a β-barrel transmembrane domain, both proteins also contain a short N-terminal periplasmic domain that, in Intimin, includes a lysin motif (LysM), which is thought to mediate binding to peptidoglycan. We show that the periplasmic domain of Intimin does bind to peptidoglycan both in vitro and in vivo, but only under acidic conditions. We were able to determine a dissociation constant of 0.8 μM for this interaction, whereas the Invasin periplasmic domain, which lacks a LysM, bound only weakly in vitro and failed to bind peptidoglycan in vivo. We present the solution structure of the Intimin LysM, which has an additional α-helix conserved within inverse autotransporter LysMs but lacking in others. In contrast to previous reports, we demonstrate that the periplasmic domain of Intimin mediates dimerisation. We further show that dimerisation and peptidoglycan binding are general features of LysM-containing inverse autotransporters. Peptidoglycan binding by the periplasmic domain in the infection process may aid in resisting mechanical and chemical stress during transit through the gastrointestinal tract.
    Molecular Microbiology 10/2014; 95(1). DOI:10.1111/mmi.12840 · 4.42 Impact Factor
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    ABSTRACT: Yersinia adhesin A (YadA) belongs to a class of bacterial adhesins that form trimeric structures. Their mature form contains a passenger domain and a C-terminal β-domain that anchors the protein in the outer membrane (OM). Little is known about how precursors of such proteins cross the periplasm and assemble into the OM. In the present study we took advantage of the evolutionary conservation in the biogenesis of β-barrel proteins between bacteria and mitochondria. We previously observed that upon expression in yeast cells, bacterial β-barrel proteins including the transmembrane domain of YadA assemble into the mitochondrial OM. In the current study we found that when expressed in yeast cells both the monomeric and trimeric forms of full-length YadA were detected in mitochondria but only the trimeric species was fully integrated into the OM. The oligomeric form was exposed on the surface of the organelle in its native conformation and maintained its capacity to adhere to host cells. The co-expression of YadA with a mitochondria-targeted form of the bacterial periplasmic chaperone Skp, but not with SurA or SecB, resulted in enhanced levels of both forms of YadA. Taken together, these results indicate that the proper assembly of trimeric autotransporter can occur also in a system lacking the lipoproteins of the BAM machinery and is specifically enhanced by the chaperone Skp.
    Journal of Biological Chemistry 09/2014; 289(43). DOI:10.1074/jbc.M114.565655 · 4.57 Impact Factor
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    ABSTRACT: Mutations in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) play an important role in the pathogenesis of Crohn's disease. NOD2 is an intracellular pattern recognition receptor (PRR) that senses bacterial peptidoglycan (PGN) structures, e.g., muramyl dipeptide (MDP). Here we focused on the effect of more-cross-linked, polymeric PGN fragments (PGNpol) in the activation of the innate immune system. In this study, the effect of combined NOD2 and Toll-like receptor 2 (TLR2) stimulation was examined compared to single stimulation of the NOD2 receptor alone. PGNpol species derived from a lipoprotein-containing Staphylococcus aureus strain (SA113) and a lipoprotein-deficient strain (SA113 Δlgt) were isolated. While PGNpol constitutes a combined NOD2 and TLR2 ligand, lipoprotein-deficient PGNpolΔlgt leads to activation of the immune system only via the NOD2 receptor. Murine bone marrow-derived dendritic cells (BMDCs), J774 cells, and Mono Mac 6 (MM6) cells were stimulated with these ligands. Cytokines (interleukin-6 [IL-6], IL-12p40, and tumor necrosis factor alpha [TNF-α]) as well as DC activation and maturation parameters were measured. Stimulation with PGNpolΔlgt did not lead to enhanced cytokine secretion or DC activation and maturation. However, stimulation with PGNpol led to strong cytokine secretion and subsequent DC maturation. These results were confirmed in MM6 and J774 cells. We showed that the NOD2-mediated activation of DCs with PGNpol was dependent on TLR2 costimulation. Therefore, signaling via both receptors leads to a more potent activation of the immune system than that with stimulation via each receptor alone.
    Infection and immunity 08/2014; 82(11):4681-4688. DOI:10.1128/IAI.02043-14 · 3.73 Impact Factor
  • Evelina Tacconelli · Andreas Peschel · Ingo B Autenrieth
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    ABSTRACT: Translation research strategy in infectious diseases, combining the results from basic research with patient-orientated research, aims to bridge the gap between laboratory findings and clinical infectious disease practice to improve disease management. In an era of increasing antimicrobial resistance, there are four main areas of clinical and scientific uncertainty that need to be urgently addressed by translational research: (i) early diagnosis of antibiotic-resistant infections and the appropriateness of empirical antibiotic therapy; (ii) the identification of reservoirs of antibiotic-resistant pathogens; (iii) the development of new antibiotics with lower propensities to evoke resistance; and (iv) the development of new non-antibiotic drugs to be used in the prevention of the spread of resistant bacterial strains. Strict European collaboration among major stakeholders is therefore essential. Appropriate educational tools to train a new generation of scientists with regard to a multifaceted approach to antimicrobial resistance research should be developed. Key areas include the support and implementation of European networks focused on translational research and related education activities, making potential therapeutics more attractive to investors and helping academic investigators to determine whether new molecules can be developed with clinical applicability.
    Journal of Antimicrobial Chemotherapy 07/2014; 69(11). DOI:10.1093/jac/dku244 · 5.31 Impact Factor
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    ABSTRACT: Author Summary About 20% of the human population is colonized by Staphylococcus aureus . The reservoir of S. aureus is mainly the human nose. Usually, colonization does not lead to infection and is therefore without symptoms. However, when hospitalized patients exhibit a suppressed immune system, they are at risk of getting infected by their own nasal S. aureus strain. Therefore, it is important to understand the events and mechanisms underlying colonization. Until now S. aureus nasal colonization is only partially understood. One bacterial key factor is a sugar polymer of S. aureus , termed cell wall teichoic acid (WTA), which is involved in S. aureus adhesion to cellular surfaces in the inner part of the nasal cavity. We show here that a receptor-protein, which is expressed on such cells, binds WTA and is thereby involved in adhesion of S. aureus to nasal cells. This
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    ABSTRACT: Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.
    PLoS Pathogens 05/2014; 10(5):e1004089. DOI:10.1371/journal.ppat.1004089 · 7.56 Impact Factor
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    ABSTRACT: The incidence of tuberculosis (TB) and especially multidrug-resistant TB (MDR) continues to increase alarmingly worldwide, and reliable and fast diagnosis of MDR is essential for the adequate treatment of patients. In contrast to the standard culture methods, nucleid acid amplification tests (NAATs) provide information about presence of Mycobacterium tuberculosis complex (MTBC) DNA and a potential resistance pattern within hours. We analyzed specimens of 110 patients from Nigeria comparing culture-based drug susceptibility testing (DST) to NAAT assays detecting isoniazid (INH), rifampicin (RMP) (GenoType MTBDRplus), and ethambutol (EMB) (GenoType MTBDRsl) resistance. Compared to DST, the GenoType MTBDRplus and MTBDRsl showed a specificity of 100% (86.3-100) and a sensitivity of 86% (42.1-99.6%) for detection of INH and a specificity of 100% (86.3-100) and a sensitivity of 83% (35.9-99.6%) for detection of RMP, and a sensitivity 100% (47.8-100%) for EMB resistance. However, in two strains, the NAAT assays provided false susceptible results as the mutations causing resistance were in genomic regions not covered by the probes of the GenoType MTBDRplus assay. We show that, in combination to DST, application of the GenoType MTBDRplus and GenoType MTBDRsl assays might be a useful additional tool to allow a rapid and safe diagnosis of MDR and extensively drug-resistant (XDR) MTBC.
    European Journal of Microbiology and Immunology 12/2013; 3(4):252-257. DOI:10.1556/EuJMI.3.2013.4.3
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    ABSTRACT: The intestinal microbiota is an important determinant of the mucosal response. In patients with inflammatory bowel diseases (IBD), the mucosal immune system has inappropriate interactions with the intestinal microbiota. We investigated how the composition of the intestinal microbiota affects its endotoxicity and development of colitis in mice. Germ-free C57BL/6J-Rag(1tm1Mom) (Rag1-/-) mice were colonized with 2 different types of complex intestinal microbiota. Colitis was induced in Rag1-/- mice by transfer of CD4(+)CD62L(+) T cells from C57BL/6J mice. Colonic tissues were collected and used for histologic analysis and cell isolation. Activation of lamina propria dendritic cells and T cells was analyzed by flow cytometry. Following transfer of CD4(+)CD62L(+) T cells, mice with intestinal Endo(lo) microbiota (a low proportion of Enterobacteriaceae, high proportion of Bacteroidetes, and low endotoxicity) maintained mucosal immune homoeostasis, whereas mice with highly endotoxic, Endo(hi) microbiota (a high proportion of Enterobacteriaceae and low proportion of Bacteroidetes) developed colitis. To determine whether the effects of Endo(hi) microbiota were related to the higher endotoxic activity of lipopolysaccharide (LPS), we compared LPS from Enterobacteriaceae with that of Bacteroidetes. Administration of Escherichia coli JM83 (wild-type LPS) to the mice exacerbated colitis, whereas E coli JM83+htrBPG (mutated LPS, with lower endotoxicity, similar to that of Bacteroidetes) prevented development of colitis following transfer of the T cells to mice. The endotoxicity of LPS produced by the intestinal microbiota is a determinant of whether mice develop colitis following transfer of CD4(+)CD62L(+) T cells. This finding might aid the design of novel biologics or probiotics to treat IBD.
    Gastroenterology 11/2013; 146(3). DOI:10.1053/j.gastro.2013.11.033 · 16.72 Impact Factor
  • Sabine Gröbner · Robert Lukowski · Ingo B Autenrieth · Peter Ruth
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    ABSTRACT: 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, prolonged cell swelling in wild-type (WT), but not in TLR4(-/-) bone marrow-derived (BM) DCs indicating that TLR4 signaling is essential for LPS-induced swelling. As a consequence, LPS-treatment enhanced the migratory activity along a chemokine (CCL21)-gradient in WT, but not in TLR4-deficient BMDCs suggesting that the LPS/TLR4-induced swelling response facilitates DC migration. Moreover, the role of calcium-activated potassium channels (KCa 3.1) as putative regulators of immune cell volume regulation and migration was analyzed in LPS-challenged BMDCs. We found that the LPS-induced swelling of KCa 3.1-deficient DCs was impaired when compared to WT DCs. Accordingly, the LPS-induced increase in [Ca(2+) ]i detected in WT DCs was reduced in KCa 3.1-deficient DCs. Finally, directed migration of LPS-challenged KCa 3.1-deficient DCs was low compared to WT DCs indicating that activation of KCa 3.1 is involved in LPS-induced DC migration. These findings suggest that both TLR4 and KCa 3.1 contribute to the migration of LPS-activated DCs as an important feature of the adaptive immune response.
    Microbiology and Immunology 11/2013; 58(1). DOI:10.1111/1348-0421.12116 · 1.24 Impact Factor
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    ABSTRACT: Blood stream infections (BSI) with Pseudomonas aeruginosa lead to poor clinical outcomes. The worldwide emergence and spread of metallo-beta-lactamase (MBL) producing, often multidrug-resistant organisms may further aggravate this problem. Our study aimed to investigate the effect of MBL-producing P. aeruginosa (MBL-PA) and various other resistance phenotypes on clinical outcomes. A retrospective cohort study was conducted in three German hospitals. Medical files from 2006 until 2012 were studied, and a number of 113 patients with P. aeruginosa BSI were included. The presence of VIM, IMP and NDM genes was detected using molecular techniques. Genetic relatedness was assessed through multilocus sequence typing (MLST). The effect of resistance patterns or MBL production on clinical outcomes was investigated by using multivariate Cox regression models. In-hospital mortality was significantly higher in patients with MBL-PA and multidrug-resistant P. aeruginosa. However, neither BSI with MBL-PA nor BSI with various resistance phenotypes of P. aeruginosa were independently associated with mortality or length of hospital stay. In multivariate models, the SAPS II score (HR 1.046), appropriate definitive treatment (HR range 0.25-0.26), and cardiovascular disease (HR range 0.44-0.46) were independent predictors of mortality. Concomitant infections were associated with an excess length of stay (HR < 1). Medication with appropriate antimicrobial agents at any time during the course of infection remains the key for improving clinical outcomes in patients with P. aeruginosa BSI and should be combined with a strict implementation of routine infection control measures.
    BMC Infectious Diseases 11/2013; 13(1):515. DOI:10.1186/1471-2334-13-515 · 2.61 Impact Factor

Publication Stats

4k Citations
657.63 Total Impact Points


  • 2000–2015
    • University of Tuebingen
      • • Institute of Medical Microbiology and Hygiene
      • • Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT)
      Tübingen, Baden-Württemberg, Germany
  • 2013–2014
    • Deutsches Zentrum für Infektionsforschung DZIF
      Brunswyck, Lower Saxony, Germany
  • 2003–2014
    • Universitätsklinikum Tübingen
      • Institute of Medical Microbiology and Hygiene
      Tübingen, Baden-Württemberg, Germany
  • 2012
    • Friedrich-Schiller-University Jena
      • Faculty of Biology and Pharmacy
      Jena, Thuringia, Germany
  • 2011
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1993–2010
    • University of Wuerzburg
      • • Institute for Molecular Infection Biology
      • • Institute for Hygiene and Microbiology
      Würzburg, Bavaria, Germany
  • 2008
    • Max Planck Institute for Developmental Biology
      • Department of Protein Evolution
      Tübingen, Baden-Württemberg, Germany
  • 2006
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1998–2001
    • Ludwig-Maximilian-University of Munich
      • Max-von-Pettenkofer Institute for Hygiene and Medical Microbiology
      München, Bavaria, Germany
  • 1999–2000
    • Max von Pettenkofer-Institut
      München, Bavaria, Germany