Design of pYD1-20ipaD plasmid for therapeutic yeast engineering Take all the considerations above, we put yeasts into our plan list. This established surface display system largely reduces the engineering difficulty and increases the reliability of our engineering. Moreover, previous works have successfully developed a mature Aga proteins yeast surface display system, which has been put to practical use in vaccine selection and sorting 23 24. With all these features, yeasts have been considered to be safe by Food and Drug Administration for a long time.Īpart from our treatment strategy, this probiotic has been engineered as new conceptual drugs for other diseases treatment, such as vaginal infections, diarrhea, and irritable bowel syndrome (IBS) 21 22.Ĭompared to other prokaryotic probiotics, the eukaryotic yeast could support more complex protein folding, which is favorable for the generation of antibodies of interest. ![]() ![]() Last but not least, the already-annotated genome makes it an excellent model organism for molecular biology research 20. Its facultative anaerobic feature enables it to make fluffy bread 18.Īlso, its variable metabolism pathways make it a good agent for alcohol fermentation and wine production 19. Saccharomyces cerevisiae, or baker's yeast, is widely used in the food industry and scientific research. coli, and other novel opportunities for passive immunization 17. Innovations in VHH-IpaD binding not only offer a solution that preserves the potency of antibiotics and microbial composition of the gut microbiome, but also illuminates targeted approaches to treat related T3SS bacteria like Salmonella and enterohemorrhagic E. Specifically, these antibodies recognize and target epitopes within the tip complex that is conserved across all pathogens that utilize type III secretion system (T3SS) to translocate effector proteins into the host cells 15. Single VH domain (VHH) antibodies displayed on the probiotic surface reduce the virulent activity of Shigella 14 through probiotic-pathogen binding while minimizing toxicity to non-targets 15 16. coli, and other novel opportunities for passive immunization 17.Įngineered probiotics with cell surface display systems are an especially promising alternative that improves Shigella eradication rates without heavy reliance on antibiotics. ![]() Besides aiding in the selection of resistant pathogens, antibiotics reduce intestinal species diversity and population, and disrupt the defensive, metabolic, and trophic functions of interdependent microbes 11.Īlthough antibiotics are able to prevent and treat infections, antibiotic exposure to the intestinal microbiota can lead to loss of colonization resistance, rendering the host more susceptible to future invasion 12 13.Įngineered probiotics with cell surface display systems are an especially promising alternative that improves Shigella eradication rates without heavy reliance on antibiotics. The use of conventional antibiotics aggravates the multidrug resistance of most Shigella strains. Shigella-related infections thereby spread rapidly, particularly in low-resource populations 7 and among vulnerable groups including children in care facilities, the homeless, and returned travelers 8 9 10 5. Shigella, as a highly infective, enteroinvasive and occasionally toxin-releasing 4 5īacterial genus, may cause severe infection and bacterial dysentery in the colorectal mucosa even with as low a dose as 10 - 100 organisms 6. In the United States alone, over 77,000 antibiotic-resistant cases were reported annually and 90% of overall Shigella cases were found to be resistant to the first choice medication ciprofloxacin 3. The Shigella species is listed as one of the eight dangerous drug-resistant bacteria 1, with associated mortalities projected to rise to 10 million globally by 2050, if not properly addressed 2.
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