@article{AmpattuHagmannLiangetal.2017,
  author    = {Ampattu, Biju Joseph and Hagmann, Laura and Liang, Chunguang and Dittrich, Marcus and Schl{\"u}ter, Andreas and Blom, Jochen and Krol, Elizaveta and Goesmann, Alexander and Becker, Anke and Dandekar, Thomas and M{\"u}ller, Tobias and Schoen, Christoph},
  title     = {Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence},
  series = {BMC Genomics},
  volume    = {18},
  journal   = {BMC Genomics},
  number    = {282},
  doi       = {10.1186/s12864-017-3616-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157534},
  year      = {2017},
  abstract  = {Background: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results: Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions: Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis.},
  language  = {en}
}
@article{MoremiMshanaKamugishaetal.2012,
  author    = {Moremi, Nyambura and Mshana, Stephen E. and Kamugisha, Erasmus and Kataraihya, Johannes B. and Tappe, Dennis and Vogel, Ulrich and Lyamuya, Eligius F. and Claus, Heike},
  title     = {Predominance of methicillin resistant Staphylococcus aureus-ST88 and new ST1797 causing wound infection and abscesses},
  series = {Journal of Infection in Developing Countries},
  volume    = {6},
  journal   = {Journal of Infection in Developing Countries},
  number    = {8},
  doi       = {10.3855/jidc.2093},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134746},
  pages     = {620-625},
  year      = {2012},
  abstract  = {Introduction: Although there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. Methodology: In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15\%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. Results: Despite considerable genetic diversity, the spa types t690 (29.1\%) and t7231 (41.6\%), as well as the sequence types (ST) 88 (54.2\%) and 1797 (29.1\%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8\%, 62.5\%, 41.6\%, 45.8\% and 50\% of the strains, respectively. Conclusion: We present the first thorough typing of MRSA at a Tanzanian hospital. Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures.},
  language  = {en}
}
@article{KoziolJareroOlsonetal.2016,
  author    = {Koziol, Uriel and Jarero, Francesca and Olson, Peter D. and Brehm, Klaus},
  title     = {Comparative analysis of Wnt expression identifies a highly conserved developmental transition in flatworms},
  series = {BMC Biology},
  volume    = {14},
  journal   = {BMC Biology},
  number    = {10},
  doi       = {10.1186/s12915-016-0233-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146566},
  year      = {2016},
  abstract  = {Background Early developmental patterns of flatworms are extremely diverse and difficult to compare between distant groups. In parasitic flatworms, such as tapeworms, this is confounded by highly derived life cycles involving indirect development, and even the true orientation of the tapeworm antero-posterior (AP) axis has been a matter of controversy. In planarians, and metazoans generally, the AP axis is specified by the canonical Wnt pathway, and we hypothesized that it could also underpin axial formation during larval metamorphosis in tapeworms. Results By comparative gene expression analysis of Wnt components and conserved AP markers in the tapeworms Echinococcus multilocularis and Hymenolepis microstoma, we found remarkable similarities between the early stages of larval metamorphosis in tapeworms and late embryonic and adult development in planarians. We demonstrate posterior expression of specific Wnt factors during larval metamorphosis and show that scolex formation is preceded by localized expression of Wnt inhibitors. In the highly derived larval form of E. multilocularis, which proliferates asexually within the mammalian host, we found ubiquitous expression of posterior Wnt factors combined with localized expression of Wnt inhibitors that correlates with the asexual budding of scoleces. As in planarians, muscle cells are shown to be a source of secreted Wnt ligands, providing an explanation for the retention of a muscle layer in the immotile E. multilocularis larva. Conclusions The strong conservation of gene expression between larval metamorphosis in tapeworms and late embryonic development in planarians suggests, for the first time, a homologous developmental period across this diverse phylum. We postulate these to represent the phylotypic stages of these flatworm groups. Our results support the classical notion that the scolex is the true anterior end of tapeworms. Furthermore, the up-regulation of Wnt inhibitors during the specification of multiple anterior poles suggests a mechanism for the unique asexual reproduction of E. multilocularis larvae.},
  language  = {en}
}
@phdthesis{HagmanngebKischkies2016,
  author    = {Hagmann [geb. Kischkies], Laura Violetta},
  title     = {Stringent response regulation and its impact on ex vivo survival in the commensal pathogen \(Neisseria\) \(meningitidis\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144352},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Neisseria meningitidis is a commensal bacterium which sometimes causes serious disease in humans. Recent studies in numerous human pathogenic bacteria have shown that the stringent response contributes to bacterial virulence. Therefore, this study analyzed the regulation of the stringent response in meningococci and in particular of RelA as well as its contribution to ex vivo fitness in a strain- and condition- dependent manner by using the carriage strain α522 and the hyperinvasive strain MC58 in different in vitro and ex vivo conditions. Growth experiments revealed that both wild-type strains were almost indistinguishable in their ex vivo phenotypes. However, quantitative real time PCR (qRT-PCR) found differences in the gene expression of relA between both strains. Furthermore, in contrast to the MC58 RelA mutant strain α522 deficient in RelA was unable to survive in human whole blood, although both strains showed the same ex vivo phenotypes in saliva and cerebrospinal fluid. Moreover, strain α522 was depended on a short non-coding AT-rich repeat element (ATRrelA) in the promoter region of relA to survive in human blood. Furthermore, cell culture experiments with human epithelial cells revealed that in both strains the deletion of relA resulted in a significantly decreased invasion rate while not significantly affecting adhesion. In order to better understand the conditional lethality of the relA deletion, computational and experimental analyses were carried out to unravel differences in amino acid biosynthetic pathways between both strains. Whereas strain MC58 is able to synthesize all 20 amino acids, strain α522 has an auxotrophy for cysteine and glutamine. In addition, the in vitro growth experiments found that RelA is required for growth in the absence of external amino acids in both strains. Furthermore, the mutant strain MC58 harboring an ATRrelA in its relA promoter region showed improved growth in minimal medium supplemented with L-cysteine and/or L-glutamine compared to the wild-type strain. Contrary, in strain α522 no differences between the wild-type and the ATRrelA deletion mutant were observed. Together this indicates that ATRrelA interferes with the complex regulatory interplay between the stringent response pathway and L-cysteine as well as L-glutamine metabolism. It further suggests that meningococcal virulence is linked to relA in a strain- and condition- depended manner. In conclusion, this work highlighted the role of the stringent response and of non-coding regulatory elements for bacterial virulence and indicates that virulence might be related to the way how meningococci accomplish growth within the host environments.},
  subject      = {Neisseria meningitidis},
  language  = {en}
}
@article{SchwerkPapandreouSchuhmannetal.2012,
  author    = {Schwerk, Christian and Papandreou, Thalia and Schuhmann, Daniel and Nickol, Laura and Borkowski, Julia and Steinmann, Ulrike and Quednau, Natascha and Stump, Carolin and Weiss, Christel and Berger, J{\"u}rgen and Wolburg, Hartwig and Claus, Heike and Vogel, Ulrich and Ishikawa, Hiroshi and Tenenbaum, Tobias and Schroten, Horst},
  title     = {Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {1},
  doi       = {10.1371/journal.pone.0030069},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131459},
  pages     = {e30069},
  year      = {2012},
  abstract  = {Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.},
  language  = {en}
}
@phdthesis{Herz2015,
  author    = {Herz, Michaela},
  title     = {Molecular characterization of the serotonin and cAMP-signalling pathways in Echinococcus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139249},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {Alveolar and cystic echinococcosis, caused by Echinococcus multilocularis and Echinococcus granulosus respectively, are severe zoonotic diseases with limited treatment options. The sole curative treatment is the surgical removal of the complete parasite material. Due to late diagnosis, chemotherapeutic treatment often is the only treatment option. Treatment is based on benzimidazoles, which merely act parasitostatic and often display strong side effects. Therefore, new therapeutic drugs are urgently needed. Evolutionarily conserved signalling pathways are known to be involved in hostparasite cross-communication, parasite development and survival. Moreover, they represent potential targets for chemotherapeutic drugs. In this context the roles of the serotonin- and cAMP-signalling pathways in Echinococcus were studied. Genes encoding serotonin receptors, a serotonin transporter and enzymes involved in serotonin biosynthesis could be identified in the E. multilocularis and E. granulosus genomes indicating that these parasites are capable of synthesizing and perceiving serotonin signals. Also the influence of exogenous serotonin on parasite development was studied. Serotonin significantly increased metacestode vesicle formation from primary cells and re-differentiation of protoscoleces. Inhibition of serotonin transport with citalopram significantly reduced metacestode vesicle formation from primary cells and caused death of protoscoleces and metacestodes. Furthermore, it could be shown that serotonin increased phosphorylation of protein kinase A substrates. Taken together, these results show that serotonin and serotonin transport are essential for Echinococcus development and survival. Consequently, components of the serotonin pathway represent potential drug targets. In this work the cAMP-signalling pathway was researched with focus on G-protein coupled receptors and adenylate cyclases. 76 G-protein coupled receptors, including members of all major families were identified in the E. multilocularis genome. Four genes homologous to adenylate cyclase IX were identified in the E. multilocularis genome and three in the E. granulosus genome. While glucagon caused no significant effects, the adenylate cyclase activator forskolin and the adenylate cyclase inhibitor 2', 5' didesoxyadenosine influenced metacestode vesicle formation from primary cells, re-differentiation of protoscoleces and survival of metacestodes. It was further shown that forskolin increases phosphorylation of protein kinase A substrates, indicating that forskolin activates the cAMP-pathway also in cestodes. These results indicate that the cAMP signalling pathway plays an important role in Echinococcus development and survival. To complement this work, the influence of different media and additives on E. granulosus protoscoleces was investigated. Anaerobic conditions and the presence of FBS prolonged protoscolex survival while different media influenced protoscolex activation and development. Taken together, this work provided important insights into developmental processes in Echinococcus and potential drug targets for echinococcosis chemotherapy.},
  subject      = {Serotonin},
  language  = {en}
}
@article{NonoPletinckxLutzetal.2012,
  author    = {Nono, Justin Komguep and Pletinckx, Katrien and Lutz, Manfred B. and Brehm, Klaus},
  title     = {Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {6},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {2},
  doi       = {10.1371/journal.pntd.0001516},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134280},
  pages     = {e1516},
  year      = {2012},
  abstract  = {Background: Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC) are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E. multilocularis, by excretory/secretory (E/S)-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. Methodology/Principal Findings: We established cultivation systems for exposing DC to live material from early (oncosphere), chronic (metacestode) and late (protoscolex) infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naive T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. Conclusions: This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The induction of CD4+CD25+Foxp3+ T cells through metacestode E/S-products suggests that these cells fulfill an important role for parasite persistence during chronic echinococcosis.},
  language  = {en}
}
@article{BijuSchwarzLinkeetal.2011,
  author    = {Biju, Joseph and Schwarz, Roland and Linke, Burkhard and Blom, Jochen and Becker, Anke and Claus, Heike and Goesmann, Alexander and Frosch, Matthias and M{\"u}ller, Tobias and Vogel, Ulrich and Schoen, Christoph},
  title     = {Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome},
  series = {PLoS One},
  volume    = {6},
  journal   = {PLoS One},
  number    = {4},
  doi       = {10.1371/journal.pone.0018441},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137960},
  pages     = {e18441},
  year      = {2011},
  abstract  = {Background Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. Principal Findings We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40\% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. Conclusions Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.},
  language  = {en}
}
@article{MaidenFrosch2012,
  author    = {Maiden, Martin C. J. and Frosch, Matthias},
  title     = {Can we, should we, eradicate the meningococcus?},
  series = {Vaccine},
  volume    = {30},
  journal   = {Vaccine},
  number    = {Suppl. 2},
  doi       = {10.1016/j.vaccine.2011.12.068},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125646},
  pages     = {B52-B56},
  year      = {2012},
  abstract  = {The eradication of infectious agents is an attractive means of disease control that, to date, has been achieved for only one human pathogen, the smallpox virus. The introduction of vaccines against Neisseria meningitidis into immunisation schedules, and particularly the conjugate polysaccharide vaccines which can interrupt transmission, raises the question of whether disease caused by this obligate human bacterium can be controlled, eliminated, or even eradicated. The limited number of meningococcal serogroups, lack of an animal reservoir, and importance of meningococcal disease are considerations in favour of eradication; however, the commensal nature of most infections, the high diversity of meningococcal populations, and the lack of comprehensive vaccines are all factors that suggest that this is not feasible. Indeed, any such attempt might be harmful by perturbing the human microbiome and its interaction with the immune system. On balance, the control and possible elimination of disease caused by particular disease-associated meningococcal genotypes is a more achievable and worthwhile goal.},
  language  = {en}
}
@article{FraunholzBernhardtSchuldesetal.2013,
  author    = {Fraunholz, Martin and Bernhardt, J{\"o}rg and Schuldes, J{\"o}rg and Daniel, Rolf and Hecker, Michael and Sinh, Bhanu},
  title     = {Complete Genome Sequence of Staphylococcus aureus 6850, a Highly Cytotoxic and Clinically Virulent Methicillin-Sensitive Strain with Distant Relatedness to Prototype Strains},
  series = {Genome Announcements},
  volume    = {1},
  journal   = {Genome Announcements},
  number    = {5},
  doi       = {10.1128/genomeA.00775-13},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129294},
  pages     = {e00775-13},
  year      = {2013},
  abstract  = {Staphylococcus aureus is a frequent human commensal bacterium and pathogen. Here we report the complete genome sequence of strain 6850 (spa type t185; sequence type 50 [ST50]), a highly cytotoxic and clinically virulent methicillin-sensitive strain from a patient with complicated S. aureus bacteremia associated with osteomyelitis and septic arthritis.},
  language  = {en}
}
@article{MarcusVogelSchubertetal.2013,
  author    = {Marcus, U. and Vogel, U. and Schubert, A. and Claus, H. and Baetzing-Feigenbaum, J. and Hellenbrand, W. and Wichmann, O.},
  title     = {A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013},
  series = {Eurosurveillance},
  volume    = {18},
  journal   = {Eurosurveillance},
  number    = {28},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131711},
  pages     = {6-8},
  year      = {2013},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{HarrisonClausJiangetal.2013,
  author    = {Harrison, Odile B. and Claus, Heike and Jiang, Ying and Bennett, Julia S. and Bratcher, Holly B. and Jolley, Keith A. and Corton, Craig and Care, Rory and Poolman, Jan T. and Zollinger, Wendell D. and Frasch, Carl E. and Stephens, David S. and Feavers, Ian and Frosch, Matthias and Parkhill, Julian and Vogel, Ulrich and Quail, Michael A. and Bentley, Stephen D. and Maiden, Martin C. J.},
  title     = {Description and Nomenclature of Neisseria meningitidis Capsule Locus},
  series = {Emerging Infectious Diseases},
  volume    = {19},
  journal   = {Emerging Infectious Diseases},
  number    = {4},
  doi       = {10.3201/eid1904.111799},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131703},
  pages     = {566-573},
  year      = {2013},
  abstract  = {Pathogenic Neisseria meningitidis isolates contain a polysaccharide capsule that is the main virulence determinant for this bacterium. Thirteen capsular polysaccharides have been described, and nuclear magnetic resonance spectroscopy has enabled determination of the structure of capsular polysaccharides responsible for serogroup specificity. Molecular mechanisms involved in N. meningitidis capsule biosynthesis have also been identified, and genes involved in this process and in cell surface translocation are clustered at a single chromosomal locus termed cps. The use of multiple names for some of the genes involved in capsule synthesis, combined with the need for rapid diagnosis of serogroups commonly associated with invasive meningococcal disease, prompted a requirement for a consistent approach to the nomenclature of capsule genes. In this report, a comprehensive description of all N. meningitidis serogroups is provided, along with a proposed nomenclature, which was presented at the 2012 XVIIIth International Pathogenic Neisseria Conference.},
  language  = {en}
}
@article{AtanasovBenkertThelenetal.2013,
  author    = {Atanasov, Georgi and Benkert, Christoph and Thelen, Armin and Tappe, Dennis and Frosch, Matthias and Teichmann, Dieter and Barth, Thomas F. E. and Wittekind, Christian and Schubert, Stefan and Jonas, Sven},
  title     = {Alveolar echinococcosis-spreading disease challenging clinicians: A case report and literature review},
  series = {World Journal of Gastroenterology},
  volume    = {19},
  journal   = {World Journal of Gastroenterology},
  number    = {26},
  doi       = {10.3748/wjg.v19.i26.4257},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131525},
  pages     = {4257-4261},
  year      = {2013},
  abstract  = {Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging.},
  language  = {en}
}
@article{TappeHaeuplerSchaeferetal.2013,
  author    = {Tappe, Dennis and Haeupler, Alexandra and Sch{\"a}fer, Hansj{\"o}rg and Racz, Paul and Cramer, Jakob P. and Poppert, Sven},
  title     = {Armillifer armillatus Pentastomiasis in African Immigrant, Germany},
  series = {Emerging Infectious Diseases},
  volume    = {19},
  journal   = {Emerging Infectious Diseases},
  number    = {3},
  doi       = {10.3201/eid1903.121508},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129054},
  pages     = {507-508},
  year      = {2013},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{GeyerChalmersMacKintoshetal.2013,
  author    = {Geyer, Kathrin K. and Chalmers, Iain W. and MacKintosh, Neil and Hirst, Julie E. and Geoghegan, Rory and Badets, Mathieu and Brophy, Peter M. and Brehm, Klaus and Hoffmann, Karl F.},
  title     = {Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes},
  series = {BMC Genomics},
  volume    = {14},
  journal   = {BMC Genomics},
  number    = {462},
  issn      = {1471-2164},
  doi       = {10.1186/1471-2164-14-462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121892},
  year      = {2013},
  abstract  = {Background: The phylum Platyhelminthes (flatworms) contains an important group of bilaterian organisms responsible for many debilitating and chronic infectious diseases of human and animal populations inhabiting the planet today. In addition to their biomedical and veterinary relevance, some platyhelminths are also frequently used models for understanding tissue regeneration and stem cell biology. Therefore, the molecular (genetic and epigenetic) characteristics that underlie trophic specialism, pathogenicity or developmental maturation are likely to be pivotal in our continued studies of this important metazoan group. Indeed, in contrast to earlier studies that failed to detect evidence of cytosine or adenine methylation in parasitic flatworm taxa, our laboratory has recently defined a critical role for cytosine methylation in Schistosoma mansoni oviposition, egg maturation and ovarian development. Thus, in order to identify whether this epigenetic modification features in other platyhelminth species or is a novelty of S. mansoni, we conducted a study simultaneously surveying for DNA methylation machinery components and DNA methylation marks throughout the phylum using both parasitic and non-parasitic representatives. Results: Firstly, using both S. mansoni DNA methyltransferase 2 (SmDNMT2) and methyl-CpG binding domain protein (SmMBD) as query sequences, we illustrate that essential DNA methylation machinery components are well conserved throughout the phylum. Secondly, using both molecular (methylation specific amplification polymorphism, MSAP) and immunological (enzyme-linked immunoabsorbent assay, ELISA) methodologies, we demonstrate that representative species (Echinococcus multilocularis, Protopolystoma xenopodis, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica and Polycelis nigra) within all four platyhelminth classes (Cestoda, Monogenea, Trematoda and 'Turbellaria') contain methylated cytosines within their genome compartments. Conclusions: Collectively, these findings provide the first direct evidence for a functionally conserved and enzymatically active DNA methylation system throughout the Platyhelminthes. Defining how this epigenetic feature shapes phenotypic diversity and development within the phylum represents an exciting new area of metazoan biology.},
  language  = {en}
}
@article{LichteneggerBinaRoieretal.2014,
  author    = {Lichtenegger, Sabine and Bina, Isabelle and Roier, Sandro and Bauernfeind, Stilla and Keidel, Kristina and Schild, Stefan and Anthony, Mark and Reidl, Joachim},
  title     = {Characterization of lactate utilization and its implication on the physiology of Haemophilus influenzae},
  series = {International Journal of Medical Microbiology},
  volume    = {304},
  journal   = {International Journal of Medical Microbiology},
  number    = {3-4},
  doi       = {10.1016/j.ijmm.2014.02.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121335},
  pages     = {490-8},
  year      = {2014},
  abstract  = {Haemophilus influenzae is a Gram-negative bacillus and a frequent commensal of the human nasopharynx. Earlier work demonstrated that in H. influenzae type b, l-lactate metabolism is associated with serum resistance and in vivo survival of the organism. To further gain insight into lactate utilization of the non-typeable (NTHi) isolate 2019 and laboratory prototype strain Rd KW20, deletion mutants of the l-lactate dehydrogenase (lctD) and permease (lctP) were generated and characterized. It is shown, that the apparent KM of l-lactate uptake is 20.1μM as determined for strain Rd KW20. Comparison of the COPD isolate NTHi 2019-R with the corresponding lctP knockout strain for survival in human serum revealed no lactate dependent serum resistance. In contrast, we observed a 4-fold attenuation of the mutant strain in a murine model of nasopharyngeal colonization. Characterization of lctP transcriptional control shows that the lactate utilization system in H. influenzae is not an inductor inducible system. Rather negative feedback regulation was observed in the presence of l-lactate and this is dependent on the ArcAB regulatory system. Additionally, for 2019 it was found that lactate may have signaling function leading to increased cell growth in late log phase under conditions where no l-lactate is metabolized. This effect seems to be ArcA independent and was not observed in strain Rd KW20. We conclude that l-lactate is an important carbon-source and may act as host specific signal substrate which fine tunes the globally acting ArcAB regulon and may additionally affect a yet unknown signaling system and thus may contribute to enhanced in vivo survival.},
  language  = {en}
}
@article{BrehonyTrotterRamsayetal.2014,
  author    = {Brehony, Carina and Trotter, Caronline L. and Ramsay, Mary E. and Chandra, Manosree and Jolley, Keith A. and van der Ende, Arie and Carion, Fran{\c{c}}oise and Berthelsen, Lene and Hoffmann, Steen and Harðard{\´o}ttir, Hj{\"o}rd{\´i}s and Vazques, Julio A. and Murphy, Karen and Toropainen, Maija and Cani{\c{c}}a, Manuela and Ferreira, Eugenia and Diggle, Mathew and Edwards, Giles F. and Taha, Muhamed-Kheir and Stefanelli, Paola and Kriz, Paula and Gray, Steve J. and Fox, Andrew J. and Jacobsson, Susanne and Claus, Heike and Vogel, Ulrich and Tzanakaki, Georgina and Heuberger, Sigrid and Caugant, Dominique A. and Frosch, Matthias and Maiden, Martin C. J.},
  title     = {Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development},
  series = {Clinical and Vaccine Immunology : CVI},
  volume    = {21},
  journal   = {Clinical and Vaccine Immunology : CVI},
  number    = {6},
  doi       = {10.1128/cvi.00133-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120808},
  pages     = {847-53},
  year      = {2014},
  abstract  = {New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.},
  language  = {en}
}
@article{DeogratiasMushiPaternoetal.2014,
  author    = {Deogratias, Anna-Pendo and Mushi, Martha F. and Paterno, Laurent and Tappe, Dennis and Seni, Jeremiah and Kabymera, Rogatus and Kidenya, Benson R. and Mshana, Stephen E.},
  title     = {Prevalence and determinants of Campylobacter infection among under five children with acute watery diarrhea in Mwanza, North Tanzania},
  series = {Archives of Public Health},
  volume    = {72},
  journal   = {Archives of Public Health},
  number    = {17},
  doi       = {10.1186/2049-3258-72-17},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120749},
  year      = {2014},
  abstract  = {BACKGROUND: Campylobacteriosis, a zoonotic bacterial disease observed world-wide, is becoming the most commonly recognized cause of bacterial gastroenteritis in humans. This study was done to determine the prevalence and determinants of Campylobacter infection among under-fives with acute watery diarrhea in Mwanza City, Tanzania. METHOD: This cross-sectional hospital-based study was conducted at Bugando Medical Centre (BMC) and Sekou Toure Hospital in Mwanza City. All inpatients and outpatients under-fives who met the inclusion criteria from October 2012 to April 2013 were enrolled in the study. Demographic and clinical data were obtained using standardized data collection tools. Stool samples were collected for gram staining and culture for Campylobacter spp. on Preston selective agar media. In addition, blood slides for malaria and HIV tests were done to all patients. RESULTS: A total of 300 children were enrolled with a median age of 12 [interquartile range, 8-19] months. Of these, 169 (56.5\%) were from BMC and 131 (43.7\%) from Sekou-Toure hospital. One hundred and seventy (56.7\%) of the participating children were male. Of 300 under-fives with acute watery diarrhea, 29 patients (9.7\%) were found to have Campylobacter infection. A significant higher number of children with Campylobacter infection were found in Sekou Toure hospital compared to BMC [16.0\% (21/29) versus 4.7\% (8/29), p = 0.002)]. Age above 2 years was independently found to predict campylobacter infection (OR: 2.9, 95\% CI 1.1-7.7, p = 0.0037). Of 30 patients with a positive blood slide for Plasmodium falciparum, 20.0\% were also positive for Campylobacter infection (OR: 3.9, 95\% CI 1.2-10.1, p = 0.021). CONCLUSION: Campylobacter infection shows a comparatively low prevalence in under-fives with acute watery diarrhea in Mwanza city and is independently associated with positive slides for malaria and an age above 2 years. Further studies are needed to type the most prevalent Campylobacter species and to determine their antibiotic susceptibility pattern.},
  language  = {en}
}
@article{BrehmKoziol2014,
  author    = {Brehm, Klaus and Koziol, Uriel},
  title     = {On the importance of targeting parasite stem cells in anti-echinococcosis drug development},
  series = {Parasite},
  volume    = {21},
  journal   = {Parasite},
  issn      = {1252-607X},
  doi       = {10.1051/parasite/2014070},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118030},
  pages     = {72},
  year      = {2014},
  abstract  = {The life-threatening diseases alveolar and cystic echinococcoses are caused by larvae of the tapeworms Echinococcus multilocularis and E. granulosus, respectively. In both cases, intermediate hosts, such as humans, are infected by oral uptake of oncosphere larvae, followed by asexual multiplication and almost unrestricted growth of the metacestode within host organs. Besides surgery, echinococcosis treatment relies on benzimidazole-based chemotherapy, directed against parasite beta-tubulin. However, since beta-tubulins are highly similar between cestodes and humans, benzimidazoles can only be applied at parasitostatic doses and are associated with adverse side effects. Mostly aiming at identifying alternative drug targets, the nuclear genome sequences of E. multilocularis and E. granulosus have recently been characterized, revealing a large number of druggable targets that are expressed by the metacestode. Furthermore, recent cell biological investigations have demonstrated that E. multilocularis employs pluripotent stem cells, called germinative cells, which are the only parasite cells capable of proliferation and which give rise to all differentiated cells. Hence, the germinative cells are the crucial cell type mediating proliferation of E. multilocularis, and most likely also E. granulosus, within host organs and should also be responsible for parasite recurrence upon discontinuation of chemotherapy. Interestingly, recent investigations have also indicated that germinative cells might be less sensitive to chemotherapy because they express a beta-tubulin isoform with limited affinity to benzimidazoles. In this article, we briefly review the recent findings concerning Echinococcus genomics and stem cell research and propose that future research into anti-echinococcosis drugs should also focus on the parasite's stem cell population.},
  language  = {en}
}
@article{SchoenKischkiesEliasetal.2014,
  author    = {Schoen, Christoph and Kischkies, Laura and Elias, Johannes and Ampattu, Biju Joseph},
  title     = {Metabolism and virulence in Neisseria meningitidis},
  doi       = {10.3389/fcimb.2014.00114},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113118},
  year      = {2014},
  abstract  = {A longstanding question in infection biology addresses the genetic basis for invasive behavior in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.},
  language  = {en}
}