Listeria monocytogenes Traffics from Maternal Organs to the Placenta and Back

Abstract

Infection with Listeria monocytogenes is a significant health problem during pregnancy. This study evaluates the role of trafficking between maternal organs and placenta in a pregnant guinea pig model of listeriosis. After intravenous inoculation of guinea pigs, the initial ratio of bacteria in maternal organs to placenta was 10³–10⁴:1. Rapid increase of bacteria in the placenta changed the ratio to 1:1 after 24 h. Utilizing two wild-type strains, differentially marked by their susceptibility to erythromycin, we found that only a single bacterium was necessary to cause placental infection, and that L. monocytogenes trafficked from maternal organs to the placenta in small numbers. Surprisingly, bacteria trafficked in large numbers from the placenta to maternal organs. Bacterial growth, clearance, and transport between organs were simulated with a mathematical model showing that the rate of bacterial clearance relative to the rate of bacterial replication in the placenta was sufficient to explain the difference in the course of listeriosis in pregnant versus nonpregnant animals. These results provide the basis for a new model where the placenta is relatively protected from infection. Once colonized, the placenta becomes a nidus of infection resulting in massive reseeding of maternal organs, where L. monocytogenes cannot be cleared until trafficking is interrupted by expulsion of the infected placental tissues. Listeria monocytogenes is a bacterial pathogen that can cause invasive disease in predisposed individuals, including pregnant women and immunocompromised individuals. During pregnancy, listeriosis leads to spontaneous abortion, preterm labor, or neonatal disease. Tropism of L. monocytogenes to the placenta and maternal immunosuppression, have been hypothesized to be the cause of the susceptibility to listeriosis during pregnancy. This study presents a series of experiments in a pregnant guinea pig model of listeriosis and mathematical simulation of the infection, which led the authors to propose a new model. A single bacterium is sufficient to cause placental infection. Due to decreased clearance in the placenta there is a strong increase of bacteria in the placental compartment, which becomes a nidus of infection leading to continuous seeding of maternal organs. Thus, the increase of bacteria in maternal organs is not due to immunosuppression but to efflux of L. monocytogenes from the placenta. This process will be interrupted by expulsion of the infected feto-placental tissues. Therefore, spontaneous abortion and prematurity can be regarded as survival mechanisms for the mother. Furthermore, this study hypothesizes that expulsion of the infected placenta may be important for the natural history of listeriosis.