Listeria motility increases the efficiency of epithelial invasion during intestinal infection

• Published in: PLoS pathogens Vol. 18; no. 12; p. e1011028
• Main Authors: Wortel, Inge M N, Kim, Seonyoung, Liu, Annie Y, Ibarra, Enid C, Miller, Mark J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2022; Public Library of Science (PLoS)
• Subjects: Animals; Bacteria; Bacterial infections; Bacterial Proteins - metabolism; Biology and Life Sciences; Causes of; Cell-mediated immunity; Confidence intervals; Development and progression; E-cadherin; Efficiency; Epithelial cells; Epithelium; Experiments; Food; Food contamination; Food contamination & poisoning; Gastroenteritis; Goblet cells; Health aspects; Host-bacteria relationships; Host-pathogen interactions; Humans; Hypotheses; Imaging; Immunity (cell-mediated); Infections; Ingestion; Intestinal Diseases; Intestine; Intestines - microbiology; Laboratory animals; Leukocytes (neutrophilic); Listeria; Listeria monocytogenes; Listeriosis; Livestock; Low temperature; Medicine and Health Sciences; Mice; Microbiological research; Microscopy; Mortality; Motility; Pathogenesis; Pathogens; Phagocytes; Phagocytosis; Physiological aspects; Room temperature; Salmonella; Simulation; Soil contamination; Soil water; Temperature preferences; Virulence; Netherlands
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011028

Listeria monocytogenes (Lm) is a food-borne pathogen that causes severe bacterial gastroenteritis, with high rates of hospitalization and mortality. Lm is ubiquitous in soil, water and livestock, and can survive and proliferate at low temperatures. Following oral ingestion of contaminated food, Lm crosses the epithelium through intestinal goblet cells in a mechanism mediated by Lm InlA binding host E-cadherin. Importantly, human infections typically occur with Lm growing at or below room temperature, which is flagellated and motile. Even though many important human bacterial pathogens are flagellated, little is known regarding the effect of Lm motility on invasion and immune evasion. Here, we used complementary imaging and computer modeling approaches to test the hypothesis that bacterial motility helps Lm locate and engage target cells permissive for invasion. Imaging explanted mouse and human intestine, we showed that Lm grown at room temperature uses motility to scan the epithelial surface and preferentially attach to target cells. Furthermore, we integrated quantitative parameters from our imaging experiments to construct a versatile "layered" cellular Potts model (L-CPM) that simulates host-pathogen dynamics. Simulated data are consistent with the hypothesis that bacterial motility enhances invasion by allowing bacteria to search the epithelial surface for their preferred invasion targets. Indeed, our model consistently predicts that motile bacteria invade twice as efficiently over the first hour of infection. We also examined how bacterial motility affected interactions with host cellular immunity. In a mouse model of persistent infection, we found that neutrophils migrated to the apical surface of the epithelium 5 hours post infection and interacted with Lm. Yet in contrast to the view that neutrophils "hunt" for bacteria, we found that these interactions were driven by motility of Lm-which moved at least ~50x faster than neutrophils. Furthermore, our L-CPM predicts that motile bacteria maintain their invasion advantage even in the presence of host phagocytes, with the balance between invasion and phagocytosis governed almost entirely by bacterial motility. In conclusion, our simulations provide insight into host pathogen interaction dynamics at the intestinal epithelial barrier early during infection.