HORSE SPECIES SYMPOSIUM: A novel approach to monitoring pathogen progression during uterine and placental infection in the mare using bioluminescence imaging technology and lux-modified bacteria1,2

Abstract

Uterine and placental infections are the leading cause of abortion, stillbirth, and preterm delivery in the mare. Whereas uterine and placental infections in women have been studied extensively, a comprehensive examination of the pathogenic processes leading to this unsatisfactory pregnancy outcome in the mare has yet to be completed. Most information in the literature relating to late-term pregnancy loss in mares is based on retrospective studies of clinical cases submitted for necropsy. Here we report the development and application of a novel approach, whereby transgenically modified bacteria transformed with lux genes of Xenorhabdus luminescens or Photorhabdus luminescens origin and biophotonic imaging are utilized to better understand pathogen-induced preterm birth in late-term pregnant mares. This technology uses highly sensitive bioluminescence imaging camera systems to localize and monitor pathogen progression during tissue invasion by measuring the bioluminescent signatures emitted by the lux-modified pathogens. This method has an important advantage in that it allows for the potential tracking of pathogens in vivo in real time and over time, which was hitherto impossible. Although the application of this technology in domestic animals is in its infancy, investigators were successful in identifying the fetal lungs, sinuses, nares, urinary, and gastrointestinal systems as primary tissues for pathogen invasion after experimental infection of pregnant mares with lux-modified Escherichia coli. It is important that pathogens were not detected in other vital organs, such as the liver, brain, and cardiac system. Such precision in localizing sites of pathogen invasion provides potential application for this novel approach in the development of more targeted therapeutic interventions for pathogen-related diseases in the equine and other domestic species.

Equine Placentitis in Mares Induces the Secretion of Pro-Inflammatory Cytokine eIL-1β and the Active Extracellular Matrix Metalloproteinase (MMP)-9

“…zooepidemicus, Streptococcus equisimilis , Staphylocossus spp., Corynebacterium pseudotuberculosis , and Pseudonocardia spp. ), and Gram-negative bacteria ( Escherichia coli , Pseudomonas spp., Klebsiela spp., Salmonella abortus equi, and Chlamydia ) [ 2 , 18 , 19 ], virus (gammaherpesvirus and equine herpervirus) [ 17 , 20 ], and fungus ( Aspergillus terreus ) [ 21 ]. Toll-like receptors (TLRs) in placental cells recognize the molecular pattern associated with many of these pathogenic microorganisms [ 22 ].…”

In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging

“…The in-vitro and in-vivo correlations are discussed below. To date, the relationship between detected luminescence and microbial load concentration has been used in BLI monitoring of infections caused by the Gram-negative bacteria, E. coli , 19 Citrobacter , 20 the Gram-positive bacteria Staphyloccocus aureus ( S. aureus ) (methicillin-intermediate and resistant isolates), 18 and Streptococcus pneumoniae ( S. pneumoniae ), 21 mycobacteria, 22 Candida albicans ( C. albicans ) 23,24,25,26 and even the filamentous fungi Aspergillus fumigatus ( A. fumigatus ). 27 Fig.…”

HORSE SPECIES SYMPOSIUM: Pathogenic and reproductive dysfunction in horses1

“…previously unidentified but highly contagious bacterium, Taylorella equigenitalis, a coccobacillary or bacillary gram-negative nonmotile bacterium (Platt et al, 1977;Timoney et al, 1977). Gontagious equine metritis was initially discovered in the United Kingdom and Ireland in 1977 (Powell, 1978), causing widespread panic internationally within the Thoroughbred industry due to the highly contagious nature of the disease.…”

“…These included uterine lavage 1 h before breeding, cloprostenol treatment postbreeding, cervical dilators, intrauterine chelators (i.e., Tris-EE)TA), mucolytics (i.e., dimethyl sulfoxide, kerosene, n-actyl-cysteine), corticosteroids (i.e., dexamethasone, prednisolone), and immunomodulators (i.e., cell wall extracts of Mycobacterium phlei and Propionibacterium : acnes). This presentation discussed the development and application of a novel approach, whereby transgenically modified bacteria transformed with lux genes and biophotonic imaging were utilized to better understand pathogen-induced preterm birth in lateterm pregnant mares (Ryan et al, 2011). Pathogen-induced preterm birth, with a particular emphasis on pathogen invasion during uterine infection, was the focus of a presentation given by Peter Ryan, from the Department of Pathobiology and Population Medicine at Mississippi State University (Ryan et al, 2011).…”