Dose Response of Listeria monocytogenes Invasion, Fetal Morbidity, and Fetal Mortality after Oral Challenge in Pregnant and Nonpregnant Mongolian Gerbils

Abstract

Listeria monocytogenes is a food-borne pathogen that can result in adverse pregnancy outcomes, such as stillbirth or premature delivery. The Mongolian gerbil was recently proposed as the most appropriate small-animal model of listeriosis due to its susceptibility to the same invasion pathways as humans. The objectives of this study were to investigate invasion and adverse pregnancy outcomes in gerbils orally exposed to L. monocytogenes, to compare the dose-response data to those of other animal models, and to investigate differences in the responses of pregnant versus nonpregnant gerbils. Gerbils were orally exposed to 0 (control), 10 3 , 10 5 , 10 7 , or 10 9 CFU L. monocytogenes in whipping cream. L. monocytogenes was recovered in a dose-dependent manner from fecal samples, adult organs, and pregnancy-associated tissues. Dams exposed to 10 9 CFU had more invaded organs and higher concentrations of L. monocytogenes in almost all organs than nonpregnant animals, though no differences in fecal shedding were seen between the two groups. Adverse pregnancy outcomes occurred only in the dams treated with 10 9 CFU. A 50% infectivity dose (ID 50 ) of 2.60 ؋ 10 6 CFU for fetuses was calculated by fitting the data to a logistic model. Our results suggest that the 50% lethal dose (LD 50 ) falls within the range of 5 ؋ 10 6 to 5 ؋ 10 8 CFU. This range includes the guinea pig and nonhuman primate LD 50 s, but the observation that L. monocytogenes-induced stillbirths can be seen in guinea pigs and primates exposed to lower doses than those at which stillbirths were seen in gerbils indicates that gerbils are not more sensitive to L. monocytogenes invasion.

Pregnancy‐related listeriosis

“…Even though Mongolian gerbils are akin to humans in their permissiveness to InlA and InlB pathways, fetal deaths were observed only in the highest (10 9 CFU) treatment group in pregnant gerbils, so that a dose response for fetal mortality could not be calculated (Disson et al, ; Roulo et al, ). These results show that gerbils are less sensitive than guinea pigs and nonhuman primates to listeriosis, and, thus, may not be an appropriate model to study human listeriosis during pregnancy.…”

Exploring the chicken embryo as a possible model for studying Listeria monocytogenes pathogenicity

“…There are however drawbacks when using the gerbil model: The genome sequence of gerbils has not yet been published and they are not yet as commercially available as mice. Also, despite having functional InlA and InlB pathways, it was recently shown that very high doses of Listeria (~1 × 10 9 ) were required to cause stillbirth in gerbils (Roulo et al, 2014 ).…”

Morin inhibits Listeria monocytogenes virulence in vivo and in vitro by targeting listeriolysin O and inflammation

“…LLO is a crucial virulence factor in the pathogenesis of Listeria, and the deletion of LLO can significantly inhibit bacterial escape from the phagosome and reduce the pathogenicity of the bacteria [10,11], which suggests that LLO deletion could be regarded as an important and effective target in the therapy of Listeria infections. In addition, the severe inflammatory response caused by Listeria infection also causes harm to the infected host and particularly induces a risk for abortion in pregnant women [34], which indicates that attenuating the inflammatory response could be an important strategy for the treatment of Listeria infection.…”