Listeria adhesion protein-expressing bioengineered probiotics prevent fetoplacental transmission of Listeria monocytogenes in a pregnant guinea pig model

Authors: RYAN A, VALERIE - Purdue University; BAILEY, TAYLOR - Purdue University; LIN, DONGQI - Purdue University; VEMULAPALLI, TRACY - Purdue University; COOPER, BRUCE - Purdue University; COX, ABIGAIL - Purdue University; BHUNIA, ARUN - Purdue University

Submitted to: Microbial Pathogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2021
Publication Date: 2/20/2021
Citation: Ryan A, V.E., Bailey, T.W., Lin, D., Vemulapalli, T., Cooper, B., Cox, A., Bhunia, A. 2021. Listeria adhesion protein-expressing bioengineered probiotics prevent fetoplacental transmission of Listeria monocytogenes in a pregnant guinea pig model pig model Valerie E. Ryan a, Taylor. Microbial Pathogenesis. doi.org/10.1016/j.micpath.2021.104752. https://doi.org/10.1016/j.micpath.2021.104752.
DOI: https://doi.org/10.1016/j.micpath.2021.104752

Interpretive Summary: Pregnancy is a high-risk factor for the foodborne pathogen Listeria monocytogenes (Lm), which causes spontaneous abortion, premature birth, or stillbirth. The primary route of Lm transmission is oral (foodborne), therefore, crossing the intestinal epithelial barrier is a prerequisite for systemic spread. We previously engineered the non-pathogenic bacterium, Lactobacillus casei to express the Listeria adhesion protein (LAP). This bioengineered Lactobacillus probiotic (BLP) strain protects nonpregnant mice from lethal infection, however, its ability to prevent listeriosis during pregnancy is not known. This study investigated whether BLP could prevent fetoplacental transmission of Lm in a pregnant guinea pig model. The results highlight the potential for the prevention of fetoplacental transmission of Lm by LAP-expressing BLP during pregnancy, which could play a major role in preventing adverse fetal effects in pregnant women exposed to Lm.

Technical Abstract: Pregnancy is a high-risk factor for foodborne pathogen Listeria monocytogenes (Lm), which causes abortion, premature birth, or stillbirth. The primary route of Lm transmission is oral hence intestinal epithelial barrier crossing is a prerequisite for systemic spread. Intestinal barrier crossing, in part, is attributed to the interaction of Listeria adhesion protein (LAP) with its cognate receptor, Hsp60. In a recent study, we showed that oral-dosing of bioengineered Lactobacillus casei probiotic (BLP) expressing the LAP protected nonpregnant mice from lethal infection; however, its ability to prevent listeriosis during pregnancy is not known. Therefore, we investigated whether BLP could prevent fetoplacental transmission of Lm in a pregnant guinea pig model. After 14 consecutive days on probiotic (~109 CFU/ml in drinking water), pregnant guinea pigs (gestational days 24–28) were orally challenged with Lm (9 × 108–2.5 × 109 CFU/animal) and were euthanized 72 h post-infection. Maternal mesenteric lymph node (MLN), liver, spleen, lungs, blood, and placenta, and fetal liver were analyzed for the presence/absence of Lm. All tissues/organs from Lm-challenged naïve dams and fetuses were Lm positive. Similar tissue distribution was also seen in guinea pigs that received wild-type Lactobacillus casei (LbcWT). Remarkably, Lm was absent in the maternal blood, kidney, lungs, and placenta, and fetal liver from the BLP-fed group even though the Lm was present in the maternal liver, spleen, and MLN. BLP feeding also suppressed Lm-induced inflammatory response in mothers. These data highlight the inflammatory response in mothers. These data highlight the potential for the prevention of fetoplacental transmission of Lm by LAP-expressing BLP during pregnancy.