Yeast sensors reveal chloroquine as yeast fertility drug

[摘要] English: Previous unpublished research by Kock and co-workers indicated that the antimalarial drug chloroquine (CQ) stimulates yeast sexual stages (biosensors). Consequently several indicator yeasts (Eremothecium ashbyi, Dipodascopsis uninucleata var. uninucelata, Lipomyces yamadae and Scheffersomyces stipitis) were exposed to concentration gradients of CQ in the Anti-mitochondrial Antifungal Assay (3A) system and their ascospore release mechanics were subjected to Auger architectomics. Auger architectomics is the study of the structure and atomic composition of cells by making use of Nano Scanning Auger Microscopy (NanoSAM) as well as other techniques (http://en.wikipedia.org/wiki/Auger_architectomics). Investigation of the ascospore release mechanics revealed that L. yamadae and S. stipitis were sequestrate (making use of passive ascospore release) while E. ashbyi and D. uninucleata made use of active ascospore release. The sensors of L. yamadae have smooth, spherical ascospores that are released by destruction of the sensor wall. The spherical sensors of S. stipitis each contain two brimmed ('hat-shaped) ascospores that are released when the sensor wall breaks apart. The sensors of E. ashbyi are mostly intercalary in long chains with up to sixteen sickle-shaped ascospores in each ellipsoidal sensor. The V-shaped fins at the base of each ascospore of E. ashbyi are coated with 3-hydroxy (3-OH) oxylipins, making them hydrophobic. This facilitates the movement of ascospores by water flow. The tapered tips of the ascospores pierce through the sensor wall to allow release (http://vimeo.com/61521401). In D. Uninucleata, the inside surface of the sensors are lined with flexible sheaths, surrounding the ascospores inside the central channel. Inflation of the sheaths due to water uptake, generates turgor pressure that forces the ascospores out of the sensor. This is in sharp contrast to the morphologically similar yeast Dipodascus geniculatus, where the inflation of sheaths surrounding each individual ascospore is responsible for ascospore release. In all cases the sensors with ascospores were observed to have increased mitochondrial activity compared to surrounding cells. It was found with the 3A system that CQ is indeed a potent yeast fertility drug, having pro-fertility effects on all the yeast sensors used, including yeasts with decreased ability to sporulate due to preservation by sub-cultivation. Chloroquine caused increased formation of mature sensors of L. yamadae and S. stipitis, and increased the rate of ascospore release from the sensors of E. ashbyi and D. uninucleata. This data becomes even more compelling when considered that the S. stipitis strain used had lost the ability to sporulate prior to this study. An investigation of the relevant literature showed that the pro-fertility effects of CQ are highly conserved in the Eukarya, having similar effects on mammals (including humans) as well as the malaria causing parasite Plasmodium falciparum. This highlights the need to re-evaluate future and current CQ based treatment regimes.

[发布机构] University of the Free State