Sanguinarine, a plant derived compound, possesses the structural capacity for antischistosomal activity. In order to gain a better understanding of how sanguinarine attacks Schistosoma cells and inhibits their function, we modeled-using the open source MolView web application-the sanguinarine compound.

Sanguinarine, a polycyclic quaternary ammonium compound, has antioxidant properties used to kill the worms at concentrations of 10 µm in 6 hours (Zhang et al 12). Sanguinarine paralyzes the worms through the nervous system. The toxin, a benzophenanthridine alkaloid, kills Schistosoma cells and was found to target the sodium-potassium ATPase transmembrane protein. The normal function of sodium-potassium ATPase is to maintain equilibrium and inhibits as a Na+ and K+ pump to maintain homeostasis (Singh et al 22). These ions are pumped through the process of ATP. However, with sanguinarine targeting schistosomal activity, its primary objective is not to maintain equilibrium, but to to mediate the toxicity allowing the worms to have abnormal cellular functions. Signaling the cells in the mitochondria to undergo apoptosis, sanguinarine causes the worm cells to undergo cell death and cell cycle arrest. In the DNA of Schistosoma cells, it inhibits microtubule polymerization and benzophenanthridine cytolytic activity. This causes Schistosoma to eventually become paralyzed.

We learnt that the treatment of the acid held clear results displaying the disintegration of the surface between the tubercles of schistosoma, but the tegumental surface remained intact. Sanguirine also causes holes, broken surfaces, and varying levels of swelling and cracking ranging from minimal to moderate throughout the anterior and posterior fissures between the tubercles. Ultimately, there were no major differences in the exterior of the worm, but major damage to the interior of schistosoma.

We aim to model the growth of our E.coli and S. cerevisiae within our bioreactor. This was accomplished by modeling growth of the co-culture system between our E.coli and S. cerevisiae constructs. Our goal and result is a theoretical proof for the capability of the bioreactor and a better understanding of the co-culture system.

Coculture Modeling

One concern in the co-culture bioreactor is microbial competition leading to the extinction or significant reduction of a certain substrate producing construct. The result would disable the sanguinarine biosynthesis process. The growth and competition of our yeast and E. coli can be modeled and analyzed for this possibility.

Assumptions

E. coli and yeast follow logistic growth, so we can discern that the populations of E. coli and S. cerevisiae will not exceed the carrying capacity of the bioreactor. Carrying capacity of the bioreactor is non-changing (by time). All cells are identical Model is unstructured (intermediate reactions and toxic effect of compounds and substrates omitted). As such, the logistic growth equations of E. coli and yeast go as follows:



E is the concentration of E. coli. Y is the concentration of yeast. However, to model each individual substrate producing cell—5 yeast cells and 2 E. coli cells—the specific equations go as follows:



Below is a graph of the expected yeast and E. coli growth for an individual cell. The actual concentration of W303 yeast in total would be higher than E. coli as there are 5 yeast constructs to the 2 modified E.coli constructs.



The equation to model pure and simple competition in a chemostat bioreactor goes as follows:



Variable D, the chemostat dilution rate can be altered to account for competition in the bioreactor to ensure that all microbes have the necessary nutrients to survive. From this, we are able to determine the amount of nutrients needed to ensure that the yeast and E. coli microbes can coexist, ensuring the viability of the SchistoGONE bioreactor.

Singh, N., & Sharma, B. (2018, March 19). Toxicological effects of berberine and Sanguinarine. Frontiers in molecular biosciences. Retrieved October 11, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867333/

Zhang, Si-Ming, and Kristen A. Coultas. "Identification of Plumbagin and Sanguinarine as Effective Chemotherapeutic Agents for Treatment of Schistosomiasis." International Journal for Parasitology: Drugs and Drug Resistance, Elsevier, 29 Dec. 2012,
https://www.sciencedirect.com/science/article/pii/S2211320712000346?via%3Dihub