Publikationsdatenbank

Pharyngeal pumping and tissue-specific transgenic P-glycoprotein expression influence macrocyclic lactone susceptibility in Caenorhabditis elegans (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Gerhard, Alexander P. (WE 13)

Krücken, Jürgen (WE 13)

Neveu, Cedric

Charvet, Claude L.

Harmache, Abdallah

von Samson-Himmelstjerna, Georg (WE 13)

Quelle

Pharmaceuticals

Bandzählung: 14

Heftzählung: 2

Seiten: Artikel 153

ISSN: 1424-8247

Sprache

Englisch

Verweise

URL (Volltext): https://www.mdpi.com/1424-8247/14/2/153

DOI: 10.3390/ph14020153

Pubmed: 33668460

Kontakt

Institut für Parasitologie und Tropenveterinärmedizin

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 62310
parasitologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Macrocyclic lactones (MLs) are widely used drugs to treat and prevent parasitic nematode infections. In many nematode species including a major pathogen of foals, Parascaris univalens, resistance against MLs is widespread, but the underlying resistance mechanisms and ML penetration routes into nematodes remain unknown. Here, we examined how the P-glycoprotein efflux pumps, candidate genes for ML resistance, can modulate drug susceptibility and investigated the role of active drug ingestion for ML susceptibility in the model nematode Caenorhabditis elegans. Wildtype or transgenic worms, modified to overexpress P. univalens PGP-9 (Pun-PGP-9) at the intestine or epidermis, were incubated with ivermectin or moxidectin in the presence (bacteria or serotonin) or absence (no specific stimulus) of pharyngeal pumping (PP). Active drug ingestion by PP was identified as an important factor for ivermectin susceptibility, while moxidectin susceptibility was only moderately affected. Intestinal Pun-PGP-9 expression elicited a protective effect against ivermectin and moxidectin only in the presence of PP stimulation. Conversely, epidermal Pun-PGP-9 expression protected against moxidectin regardless of PP and against ivermectin only in the absence of active drug ingestion. Our results demonstrate the role of active drug ingestion by nematodes for susceptibility and provide functional evidence for the contribution of P-glycoproteins to ML resistance in a tissue-specific manner.