title: Bacteria tracking by in vivo magnetic resonance imaging.
abstract: BACKGROUND
  Different non-invasive real-time imaging techniques have been developed over the last decades to study bacterial pathogenic mechanisms in mouse models by following infections over a time course. In vivo investigations of bacterial infections previously relied mostly on bioluminescence imaging (BLI), which is able to localize metabolically active bacteria, but provides no data on the status of the involved organs in the infected host organism. In this study we established an in vivo imaging platform by magnetic resonance imaging (MRI) for tracking bacteria in mouse models of infection to study infection biology of clinically relevant bacteria.
  
  
  RESULTS
  We have developed a method to label Gram-positive and Gram-negative bacteria with iron oxide nano particles and detected and pursued these with MRI. The key step for successful labeling was to manipulate the bacterial surface charge by producing electro-competent cells enabling charge interactions between the iron particles and the cell wall. Different particle sizes and coatings were tested for their ability to attach to the cell wall and possible labeling mechanisms were elaborated by comparing Gram-positive and -negative bacterial characteristics. With 5-nm citrate-coated particles an iron load of 0.015 ± 0.002 pg Fe/bacterial cell was achieved for Staphylococcus aureus. In both a subcutaneous and a systemic infection model induced by iron-labeled S. aureus bacteria, high resolution MR images allowed for bacterial tracking and provided information on the morphology of organs and the inflammatory response.
  
  
  CONCLUSIONS
  Labeled with iron oxide particles, in vivo detection of small S. aureus colonies in infection models is feasible by MRI and provides a versatile tool to follow bacterial infections in vivo. The established cell labeling strategy can easily be transferred to other bacterial species and thus provides a conceptual advance in the field of molecular MRI.
authors.affiliation: Department of Clinical Radiology, University Hospital Münster, Münster 48149, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Hoerr
authors.forename: Lorena
authors.initials: L
authors.lastname: Tuchscherr
authors.forename: Jana
authors.initials: J
authors.lastname: Hüve
authors.forename: Nadine
authors.initials: N
authors.lastname: Nippe
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
authors.forename: Nataliya
authors.initials: N
authors.lastname: Glyvuk
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Tsytsyura
authors.forename: Michael
authors.initials: M
authors.lastname: Holtkamp
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkötter
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klingauf
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.forename: Bettina
authors.initials: B
authors.lastname: Löffler
authors.forename: Cornelius
authors.initials: C
authors.lastname: Faber
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007501:Iron / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry; D010587:Phagocytosis / Q000187:drug effects; D015203:Reproducibility of Results; D013194:Staining and Labeling; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; D007501:Iron