MycoBiomDB – Record Details (MyCo_2699)

Biomarker Record Details

Database ID: MyCo_2699
DB IDMyCo_2699
TitleNeuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure
Year2016
PMID26842664
Fungal Diseases involvedIntra-amniotic Candida albicans Fungal infection
Associated Medical ConditionChorioamnionitis
GenusCandida
Speciesalbicans
OrganismCandida albicans
Ethical StatementThe study was approved by and performed according to the guidelines of the animal ethics committee of the University of Western Australia (Perth, Australia).
Site of InfectionBrain
Opportunistic invasiveNone
Sample typeBiopsy
Sample sourceTissue Supernatant
Host GroupAnimal
Host Common nameSheep
Host Scientific nameMerino ewes
Biomarker NameCAS3
Biomarker Full NameCaspase-3
Biomarker TypeDiagnostic
BiomoleculeProtein
Geographical LocationAustralia
CohortTwenty-six date-mated Merino ewes with singleton pregnancies were randomly assigned to receive an intra-amniotic injection of saline (2 mL) as a control or C. albicans (107 colony-forming units [CFU], Western Australian clinical isolate). After 2 days, an intra-amniotic/-peritoneal injection of fluconazole (30 mg per injection, Claris Life Sciences Limited, Chacharwadi-vasana, Ahmedabad- 382 213, India) or saline (controls) was administered with delivery after 1 and 3 days. Intra-amniotic injections were performed as previously described. We did not include a 5-day C. albicans-only group since previous results with this model indicated that 5 days exposure to C. albicans alone was lethal. Given the survival of the 5-day C. albicans-/fluconazoletreated group, we have concluded that fluconazole in this model increases survival.
Cohort No.26
Age GroupNone
P Valuep<0.05
SensitivityNone
SpecificityNone
Positive Predictive ValueNone
MICNone
Fold ChangeNone
PathwayNone
Disease Introduction MechanismPreterm birth is associated with chorioamnionitis which is defined as inflammation of the fetal membranes and amniotic fluid caused by microbial invasion. The microorganisms most frequently associated with this condition include Ureaplasma species, Mycoplasma hominis, and Gardnerella vaginalis, all of which most commonly originate from the lower reproductive tract. These microorganisms and/or inflammatory mediators in the amniotic cavity can cause a fetal inflammatory response syndrome (FIRS). Chorioamnionitis and subsequent FIRS are independent risk factors for adverse outcomes, including injury of the fetal brain. Adverse neurodevelopmental outcomes result from diffuse cerebral inflammation and white matter injury, periventricular leukomalacia, and intraventricular hemorrhage. These conditions are associated with a high mortality rate, and survivors are predisposed to longterm morbidity including mental retardation, impaired learning, visual disorders, and in severe cases, cerebral palsy. The pathophysiology of chorioamnionitis can also include viral and fungal species. Candida albicans (C. albicans) is a commensal fungus of the gastro-intestinal tract which can be asymptomatic in the vaginal microbiota with increasing incidence during pregnancy. Intraamniotic C. albicans infections are associated with high mortality rates and severely impaired neurodevelopmental outcomes in which the mechanisms linking fetal exposure to neurological pathologies remain essentially unstudied. We hypothesized that antenatal exposure to C. albicans caused a neuroinflammatory response and subsequent white matter injury, which we tested by exposing fetal sheep to intra-amniotic C. albicans.
TechniqueELISA
Analysis MethodELISA Based
ELISA kitsNone
Assay DataNone
Validation Techniques usedELISA, Immunohistochemistry, Immunofluorescence
Up Regulation Down RegulationIncrease
Sequence DataNone
External LinkNone