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.

Dexamethasone Increases Hippocampal Neuronal Apoptosis in a Rabbit Model of Escherichia coli Meningitis

“…Despite rapid sterilization of the CSF, worsening of clinical symptoms after initiation of antibiotic treatment during meningitis has been frequently observed, most probably as a consequence of a burst of inflammation caused by the liberation of proinflammatory bacterial compounds (2). In accord with these clinical observations, a mouse model of pneumococcal meningitis showed an immediate massive increase of glial fibrillary acidic protein as an indicator of parenchymal glial activation after onset of bacterial killing by ceftriaxone (3). Elevated levels of inflammatory mediators such as cytokines and prostaglandins are common in the CSF of infants and children with bacterial meningitis and useful in evaluating the intensity of the inflammatory process in the CNS (4,5).…”

Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae

“…S. pneumoniae Xen10 carries a stable copy of the modified Photorhabdus luminescens lux operon at a single integration site on the bacterial chromosome (40). The virulence of S. pneumoniae Xen10 is comparable to that of the parent strain (40,41). For challenge studies, S. pneumoniae 3JYP3670, which expresses PspA of family 2, clade 4, was used (10).…”

Optical imaging of bacterial infection models

“…In another study, the lungs of a mouse were infected with bioluminescent Streptococcus pneumonia by introducing the cells through the nose into the airway (Figure 2, center) [21,22]. When these same cells are introduced via an intracranial injection, they infect the brain and spine (Figure 2, right) [23,24]. In both of these cases, antibiotic treatment mitigated light output from the invading cells.…”