Undergraduate Student Albion College Albion, Michigan, United States
Anna Crysler (Albion College)| Peter Filbrandt (Albion College)| Kaitlyn Piontkowsky (Albion College)
As one of the World Health Organization’s top 10 threats to public health, antibiotic resistance greatly impacts populations all across the world, threatening healthcare, agriculture, and the lives and livelihoods of billions of people. In the U.S. alone, 2.8 million antibiotic resistant infections occur annually, resulting in over 35,000 deaths, and those numbers are expected to rise to 10 million deaths globally by 2050 without urgent action. Selective pressure from antibiotics has resulted in a plethora of mechanisms for resistance, allowing for an increasing number of bacterial infections that become severe and difficult or impossible to treat. Antibiotic resistance was observed almost as soon as the first antibiotics were discovered, so these issues are not new, yet what is currently concerning is the diversity and prevalence of resistance to “last resort” antibiotics, necessitating the development of new alternatives. Unfortunately, novel antibiotic development has been slow with the introduction of less than 10 novel classes in the last 20 years. This trend is likely to continue, as commercial investment in antibiotic development has almost completely collapsed. This is largely a result of the immense development costs that are hard to recover due to the reluctance of physicians to use new expensive antibiotics and/or the speed with which resistance to new therapeutics is observed. Two possible approaches for increasing the commercial viability of antibiotic production are to reduce development time and costs. Directed evolution methods have the potential to create novel antibiotics by meeting both of these needs. Directed evolution takes advantage of selective pressures, similar to those that drive antibiotic resistance, to select molecules with desirable properties such as antimicrobial activity. Nanobodies, which are single domain antibodies, represent a promising class of molecules for use as antimicrobials given their potential antigen specificity, size, and stability, giving rise to favorable pharmaceutical profiles. This poster focuses on the directed evolution of nanobodies for use as antibiotics and diagnostic agents using yeast surface display and a variety of cell-sorting techniques. In addition, the poster will outline target selection strategies and the unique challenges and opportunities associated with generating antimicrobial nanobodies using directed evolution techniques.
Support or Funding Information
Foundation for Undergraduate Research, Scholarship, and Creative Activity