title: Reduction of astrogliosis by early treatment of pneumococcal meningitis measured by simultaneous imaging, in vivo, of the pathogen and host response.
abstract: We developed a method for simultaneous in vivo biophotonic monitoring of pneumococcal meningitis and the accompanying neuronal injury in live transgenic mice. Streptococcus pneumoniae engineered for bioluminescence (lux) was used for direct visualization of disease progression and antibiotic treatment in a mouse model of meningitis. The host response was monitored in transgenic mice containing an inducible firefly luciferase (luc) reporter gene under transcriptional control of the mouse glial fibrillary acidic protein (GFAP) promoter. Based on the different spectra of light emission and substrate requirements for lux and luc, we were able to separately monitor the two reporters using a highly sensitive in vivo imaging system. The level of neuronal damage and recovery following antibiotic treatment was dependent on the time of treatment. This model has potential for simultaneous multiparameter monitoring and testing of therapies that target the pathogen or host response to prevent neuronal injury and recovery.
authors.affiliation: Clorox Services Company, 7200 Johnson Dr., Pleasanton, CA 94588, USA. Jagath.Kadurugamuwa@Clorox.com
authors.forename: Jagath L
authors.initials: JL
authors.lastname: Kadurugamuwa
authors.forename: Kshitij
authors.initials: K
authors.lastname: Modi
authors.forename: Olivier
authors.initials: O
authors.lastname: Coquoz
authors.forename: Brad
authors.initials: B
authors.lastname: Rice
authors.forename: Steven
authors.initials: S
authors.lastname: Smith
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Contag
authors.forename: Tony
authors.initials: T
authors.lastname: Purchio
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D017930:Genes, Reporter; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D005911:Gliosis / Q000188:drug therapy* / Q000473:pathology; D049409:Luciferases, Firefly / Q000032:analysis* / Q000235:genetics; D049408:Luminescent Agents / Q000032:analysis*; D008163:Luminescent Measurements; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D005904:Glial Fibrillary Acidic Protein; D049408:Luminescent Agents; D049409:Luciferases, Firefly