The war on superbugs: antibiotic development and the emergence of drug-resistant bacteria

Lectures: 1 session / week, 2 hours / session

At least one of the following prerequisites is required:

7.05 General Biochemistry

7.06 Cell Biology

7.08J Biological Chemistry II

Bacteria and fungi have produced antibiotics, small molecules that can prevent the growth of or kill bacteria by inhibiting essential biological pathways, as a defense mechanism long before humans walked the earth. The discovery of antibiotics and their implementation in the clinic radically changed modern medicine, saving countless lives by treating infections that were once difficult to cure, such as syphilis, strep throat and tuberculosis. Although antibiotics were once referred to as the "wonder drug" of modern medicine, a growing number of drug-resistant bacteria have emerged since the beginning of the 20th century, which has compromised their effectiveness. Furthermore, as a consequence of the introduction of diverse antibiotics, multidrug resistant bacteria have emerged, negating recent advances in eradicating bacterial infections across the globe. Scientists have successfully studied the origins of many drug-resistant bacteria, shedding light on the molecular mechanisms bacteria have evolved to persist in the presence of antibiotics. Understanding these pathways will be fundamental for the future of medicine. During this course, we will cover many aspects of antibiotics including techniques used to discover these inhibitors, their mode of action and use in medicine. For example, we will learn about the techniques used to discover antibiotics, such as penicillin and vancomycin. We will discuss antibiotic-resistant bacteria and the molecular mechanisms underlying resistance, including horizontal gene transfer, point mutations and efflux pumps. Additionally, we will learn about pioneering work to treat infections with engineered antimicrobial peptides and microbiome replacement therapies. The course will focus on the primary research literature, and we will learn practical laboratory techniques, experimental design and how to interpret data and critique the conclusions offered by authors. Students will have the opportunity to visit a local hospital to learn about the process of treatment with antibiotics and what is being done to avoid the continuous emergence of antibiotic resistance.

This class will meet once a week for two hours. The meeting time for the class will be determined by the schedules of the students interested in participating and the availability of a classroom. Each week, we will focus on a different aspect of antibiotics by discussing two papers that highlight that week's topic. We will begin the course with an introduction to antibiotics. We will briefly talk about the various classes of antibiotics, their discovery and molecular mechanisms of action. Next we will introduce the topics of the subsequent weeks to give a broad overview of the diverse topics of the course. Importantly, we will go over the general format of original research articles and present strategies to help understand and analyze the key findings. Before each class all students should have carefully read the two papers assigned for that week so that they will be able to discuss the contents in detail. We will spend the last 15 minutes of every class introducing the next week's topic (handouts will be distributed). Students are encouraged to contact the instructors with questions or concerns about any aspect of the papers before each class. During class, students will lead a discussion about the two papers; every student will be encouraged to participate. Students are required to submit a mid-semester written assignment and make an oral presentation during the last class.

The class is graded on a pass / fail basis, and grades will be based on participation in discussion every week, satisfactory completion of the written and oral assignments, and attendance.

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