Pathophysiology and Histopathology of Group B Streptococcal Sepsis in Macaca nemestrina Primates Induced after Intraamniotic Inoculation: Evidence for Bacterial Cellular Invasion

Abstract

Four pregnant Macaca nemestrina dams at 140-145 days of gestation received an intraamniotic inoculation of group B streptococci (GBS). All four premature infants were born by cesarean delivery, were bacteremic at birth, and showed symptoms of GBS sepsis similar to infected human infants with early-onset disease. Three infants did not receive antibiotics and died of GBS sepsis by 10 h of age despite mechanical ventilation and fluids for blood pressure support. Penicillin treatment of the fourth infant prolonged survival and decreased the requirement for supportive therapy. Quantitative cultures and histopathology were done on all four infants. Transmission electron microscopy of lung tissue demonstrated GBS within membrane-bound vacuoles of type I and II alveolar epithelium and interstitial fibroblasts. This model should be useful for studying the early steps in the pathogenesis of early-onset GBS infections. GBS may enter alveolar epithelial cells to transit this barrier and ultimately disseminate via the blood-stream.

Cellular Activation, Phagocytosis, and Bactericidal Activity Against Group B Streptococcus Involve Parallel Myeloid Differentiation Factor 88-Dependent and Independent Signaling Pathways

“…Shortly after the inoculation of bacteria into the parenchyma of the lung, GBS may achieve a density as high as 10 9 -10 11 CFU/g lung tissue, as confirmed in the primate model of neonatal GBS pneumonia (56). This enormous localized bacterial burden probably results from the relatively inefficient clearance of GBS by the incompletely developed neonatal immune system (57).…”

Endotoxin-Neutralizing Antimicrobial Proteins of the Human Placenta

“…Infection-related prematurity is most likely caused by an infection that ascends from the lower genital tract to the upper tract, with the end stage being a positive amniotic fluid culture (13,14). Fetal exposure to high concentrations of microorganisms leads to colonization of the fetus lung airways and subsequent pneumonia, sepsis, and meningitis (15,16). Even a trivial fetal infection can trigger an exaggerated inflammatory response, inducing cytokine cascades and resulting in the eventual demise of the neonate (17).…”

Molecular epidemiology and virulence characteristics of prevalent group A streptococci recovered from patients in northern India

“…The cell culture infection assay was performed using a conventional method with some modifications described elsewhere [25,27]. In brief, GAS strains (M1.27 and M49.4 strains) were grown at three different temperatures (25ºC, 30ºC, and 41°C) and two salt concentrations (0.3 and 0.6 M NaCl) to an OD 650 of 0.5 in THB.…”

“…Furthermore, we studied the virulence potential of GAS grown under different environmental conditions using prevalent GAS M types by measuring the in vitro proinflammatory immune response by host cells against selected GAS strains. Infection efficiency was checked using a conventional method [25] under different temperature and salt stress conditions. We observed environmentally regulated infectious behavior of GAS and variable proinflammatory immune responses by host cells.…”