@article{FriedrichRahmannWeigeletal.2010,
  author    = {Friedrich, Torben and Rahmann, Sven and Weigel, Wilfried and Rabsch, Wolfgang and Fruth, Angelika and Ron, Eliora and Gunzer, Florian and Dandekar, Thomas and Hacker, Joerg and Mueller, Tobias and Dobrindt, Ulrich},
  title     = {High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67936},
  year      = {2010},
  abstract  = {The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. Results: We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Conclusions: Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.},
  subject      = {Mikroarray},
  language  = {en}
}
@article{BielaszewskaSchillerLammersetal.2014,
  author    = {Bielaszewska, Martina and Schiller, Roswitha and Lammers, Lydia and Bauwens, Andreas and Fruth, Angelika and Middendorf, Barbara and Schmidt, M. Alexander and Tarr, Phillip I. and Dobrindt, Ulrich and Karch, Helge and Mellmann, Alexander},
  title     = {Heteropathogenic virulence and phylogeny reveal phased pathogenic metamorphosis in Escherichia coli O2:H6},
  series = {EMBO Molecular Medicine},
  volume    = {6},
  journal   = {EMBO Molecular Medicine},
  number    = {3},
  issn      = {1757-4684},
  doi       = {10.1002/emmm.201303133},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117254},
  pages     = {347-357},
  year      = {2014},
  abstract  = {Extraintestinal pathogenic and intestinal pathogenic (diarrheagenic) Escherichia coli differ phylogenetically and by virulence profiles. Classic theory teaches simple linear descent in this species, where non-pathogens acquire virulence traits and emerge as pathogens. However, diarrheagenic Shiga toxin-producing E.coli (STEC) O2:H6 not only possess and express virulence factors associated with diarrheagenic and uropathogenic E.coli but also cause diarrhea and urinary tract infections. These organisms are phylogenetically positioned between members of an intestinal pathogenic group (STEC) and extraintestinal pathogenic E.coli. STEC O2:H6 is, therefore, a 'heteropathogen,' and the first such hybrid virulent E.coli identified. The phylogeny of these E.coli and the repertoire of virulence traits they possess compel consideration of an alternate view of pathogen emergence, whereby one pathogroup of E.coli undergoes phased metamorphosis into another. By understanding the evolutionary mechanisms of bacterial pathogens, rational strategies for counteracting their detrimental effects on humans can be developed.},
  language  = {en}
}