Publication Database

Bacterial modulation by the intestinal roundworm Ascaris suum (2024)

Art

Hochschulschrift

Autor

Midha, Ankur (WE 6)

Quelle

Berlin: Mensch & Buch Verlag, 2024 — VI, 129 Seiten

ISBN: 978-3-96729-252-7

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/44961

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Background: Ascariasis is one of the most common soil-transmitted helminth infections worldwide and a considerable problem in animal agriculture. The infection is spread via the fecal- oral route and occurs following ingestions of eggs containing infective third-stage larvae. These eggs hatch, releasing larvae which then invade the host intestine and embark on a tissue migration phase which takes them through the host’s liver and lungs before returning to the small intestine. This tissue migration leads to the immune responses, pathologies, and symptoms characteristic of ascariasis. In the jejunum, the worms mature and live amongst host microbes. Current efforts to control helminth infections have been somewhat successful but have not been able to eradicate these pathogens. Thus, novel insights into their lifestyle within the host are needed to unveil new therapeutic modalities. Much remains unknown concerning their interactions with microbes in the host intestine. Therefore, this thesis aimed to unravel interactions between Ascaris and microbes by characterizing antimicrobial activities of the worms as well as the first description of the Ascaris microbiome and its key determinants by completing the following aims: 1. To determine if Ascaris nematodes release antimicrobial compounds in their excreted and secreted products. 2. To characterize the antimicrobial activities of these products. 3. To characterize the Ascaris microbiome. 4. To identify the primary determinants of Ascaris microbiome composition. Results: The excreted and secreted products of A. suum were found to contain a variety of proteins and peptides with known and predicted antimicrobial activity, including antimicrobial peptides from different families and C-type lectins. These products exhibited diverse antimicrobial activities, including bacterial growth inhibition, disruption of bacterial Biofilm formation, and agglutination. We further characterized one of the proteins secreted by Ascaris, a C-type lectin domain-containing protein we have named AsCTL-42. This lectin recapitulated the agglutination observed for Ascaris ES products and inhibited invasion of porcine intestinal epithelial cells by Salmonella Typhimurium. Finally, we characterized the microbiome of Ascaris nematodes isolated from infected pigs and determined that the nematode’s own intestinal microbiome is derived, but distinct from, the microbes present in the host jejunum. Composition of the Ascaris microbiome is driven primarily by the dominant bacteria present at the site of infection; however, certain genera are enriched in the Ascaris intestine relative to the host. Conclusions: Our results demonstrate that Ascaris acquires microbes from those present at the site of infection in the host jejunum and that these microbes are present in differential abundances in the worm relative to its host, suggesting that the worm might preferentially take up some bacteria while excluding others. Our data characterize potential mechanisms by which the worm might modulate its microbiome as well as that of its host by demonstrating antimicrobial activities of its excreted and secreted products which contain various antimicrobial effector molecules. Our data provide a foundation for further work which can assess the impacts of interactions between Ascaris, microbes, and host cells on co-infecting pathogens while determining which microbes are beneficial or harmful for the worm.