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7.341 | Fall 2022 | Undergraduate

# Microbes at War: The Mechanisms That Drive Infectious Diseases

Each Lecture Summary is based on the corresponding Readings for that week.

Week | Topics | Lecture Summaries
--- | --- | ---
1 | Welcome to the “Battlefield”— Introduction to Host-Pathogen Interactions and How to Effectively Read Journal Articles | In this introductory week, we will introduce ourselves and discuss the course logistics. We will discuss key concepts and definitions related to host-pathogen interactions. We will also examine approaches for searching, cataloging, and reading primary literature articles. The goal when reading journal articles is to be able to 1) efficiently find the main points, methods, and conclusions and 2) critically analyze the main conclusion. We will discuss strategies to accomplish these goals.
2 | Identify the Enemy—Koch’s Postulates | Koch’s postulates are a set of 4 criteria used to establish whether an organism is the cause of a specific disease. To fulfill Koch’s postulates, the microbe (1) must be found in diseased but not healthy individuals, (2) must be cultured from the diseased individual, (3) must recapitulate the disease when a healthy individual is inoculated with the cultured microorganism, and (4) must be re-isolated from the inoculated, diseased individual and matched to the original microorganism. The first paper is one of the most direct examples fulfilling Koch’s postulates, showing that the bacterium Campylobacter (now known as H. pylori) causes stomach ulcers. This paper resulted in one of the authors winning a Nobel prize! The second paper focuses on molecular analogs of Koch’s postulates—how we know a specific protein (or virulence factor) is involved in disease progression.
3 | The World’s Deadliest Infectious Disease—Tuberculosis | Tuberculosis caused by the bacterium Mycobacterium tuberculosis has shaped human health and history. Tuberculosis remains one of the world’s deadliest infections, infecting one-fourth of the world’s population and causing 1.4 million deaths per year. One of the first challenges in controlling an infectious disease is understanding the mechanism of transmission (air, object contact, or fecal/oral). Think back to the first months of COVID-19—why did we need to wear masks and was it necessary to wipe down groceries with disinfectant? With the first paper, which describes how we know that tuberculosis is air-transmittable, we will explore how scientists address questions of transmission. The second paper uses a model organism, the non-infectious bacterium Mycobacterium smegmatis, to study Mycobacterium bacterial division and considers how the mechanism of cell division impacts the use of antibiotics, a major line of defense against bacterial infections.
4 | On the Front Lines—How Bacteria Can Stake Their Claim on the Battlefield | To cause an infection, a pathogen must actually stick around and survive in a location. If the pathogen can’t survive in a niche, it can’t cause infection. To demonstrate this concept, we will focus on urinary tract infections, caused by the bacterium E. coli and affecting 50% of women throughout their lifespan. E. coli use sticky protein fibers, called adhesins, to bind sugars on the bladder surface and avoid being eliminated from the bladder during urination. Type 1 pili are a type of E. coli adhesin critical for E. coli survival in the bladder. The first paper shows the identification of the receptor for type 1 pili in the bladder. The second paper shows how E. coli uses this same adhesin in a different niche, the human gut, and how a medicinal sugar, called a mannoside, can target this interaction to eliminate the bacteria from the host. Note: Sometimes journals provide summary articles or commentaries about published articles. Such summaries can offer fun ways to see other scientist’s perspectives about the articles. If you are interested, see if you can find a few such commentaries about the second article!
5 | Not All Microbes Are Bad—Field Trip Preparation | We have been primarily focused on microbes that cause diseases. However, only a minority of microbes are disease-causing in humans. In fact, the human microbiome does a lot to protect us against diseases. For this reason, many companies are using microbes to improve health. Dove soap even advertises that it works to protect your microbiome! This week, we will shift to thinking about positive microbes and microbial technologies in relation to our field trip. We will read two papers by the founders of the company Concerto Biosciences. The first paper looks at how bacteria often interact in microbial communities in a positive manner to promote growth of the community. The second paper focuses on a new technology, Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic Acids (CARMEN). CARMEN is a technology that is able to rapidly examine large quantities of patient samples simultaneously for multiple different types of pathogens. (In the paper, the authors are able to detect 169 different human-associated viruses from patient samples!)
6 | Field Trip!!! Concerto Biosciences Written Assignment Due | This week we will visit a local start-up company, Concerto Biosciences. Many of their scientists trained here at MIT! Read more about their mission. We will talk about both science and scientific careers, and your only prep for this week is to look at the company website and think about any questions you might have about their company! Please dress appropriately for walking around a laboratory—e.g., wear closed-toe shoes this week. Additional instructions for the field trip (traveling to Concerto, clothing, etc.) will be provided prior to class.
7 | Preprint Week—and the Mysterious Hepatitis Outbreak | We have been working to hone our critical reading skills. Now is your chance to put your skills to the test. This week we will be reading preprints! As noted in our last session, preprints offer a way for scientists to post their findings before they are submitted to journals for peer review. Doing so allows authors to release new findings rapidly and to receive feedback from the broad scientific community prior to publication. However, use of preprints can go awry— since the information hasn’t undergone peer review, you need to be critical about what preprints are claiming, as it might be completely wrong! Just remember, just like any information taken from non-validated sources, preprint information might be wrong. Two common preprint servers in health sciences are BioRxiv and MedRxiv. This week, we will look at two papers from MedRxiv. Currently, there is an outbreak of hepatitis (liver inflammation) in children. This outbreak has no apparent cause! (Google “Hepatitis in children 2022” to see the latest news on this topic.) Normally hepatitis is caused by a number of known hepatitis viruses (A-E) but these were not detected in the affected children. The first paper suggests that a different virus called adeno-associated virus 2, or AAV-2, might be associated with the hepatitis outbreak. This virus commonly infects children but has never been linked to human disease. Interestingly, as AAV2 typically requires a coinfecting “helper” virus to replicate, this paper looks at an additional herpesvirus that might also be involved. The second paper identifies a specific genotype of MHC class II molecule—class II HLA allele HLA-DRB1*04:01—in infected children. MHC molecules allow antigens in foreign bodies such as viruses to be presented by antigen-presenting cells (such as dendritic cells, macrophages, and epithelial cells) to professional killing cells (such as T cells), thereby triggering the immune system to respond to the infection.
8 | Illness Is Sweeping through the Ranks—Norovirus (Winter Vomiting Bug) | Norovirus is highly contagious and causes vomiting and diarrhea. Norovirus has been known to temporarily shut down universities and cruise ships. This week we will re-example the concept of receptors that we explored during our consideration of urinary tract infections. The first paper uses a CRISPR screen to identify the receptor for murine norovirus. CRISPR screening is a modern technique that is changing the way we do science both in academic and commercial labs. The second paper explores how model organisms sometimes do not tell the whole story. This week, we will discuss the benefits of and drawbacks to using model organisms. We will also consider different types of genetic screens, what types of information such screens provide, and what limitations genetic screens have.
9 | Biological Sex, Pregnancy, and Infectious Diseases—Malaria | Malaria is caused by a human parasite, Plasmodium. Plasmodium is thought to have contributed to the fall of the Roman Empire. Malaria continues to cause millions of infections a year, most often in tropical climates. Malaria can be particularly dangerous to pregnant women and the developing fetus. The first paper describes how parity (the number of pregnancies a woman has had) impacts pregnancy-associated malaria through the production of specific antibodies. We will think about how studies are controlled and how age and biological sex are a part of this discussion. The second paper discusses co-infection of HIV and malaria, a common issue in Africa. We will consider how the first paper suggests a potential good vaccine target for pregnancy-associated malaria and how the second paper impacts our understanding of malaria treatment options
10 | Friendly Fire—How the Immune System Can Go Awry, and a Tick Bite Can Lead to Allergic Reactions to Meat Final Presentation Topic Due | The immune system is meant to protect us and does a lot of work to keep us healthy. However, sometimes the immune system has unhelpful overreactions, such as in anaphylactic shock. Today we will discuss two stories about the human immune system that proved to be surprisingly interconnected. The monoclonal antibody cetuximab was in clinical trials for treatment of colon cancer, but patients were developing anaphylactic reactions to the antibody. At the same time, a group of outdoorsy patients were developing an anaphylactic reaction to meat. It turned out that the allergic reactions to cetuximab and meat both involved a hypersensitivity reaction to a galactose-alpha-1,3-galactose (alpha-gal). Alpha-gal is a sugar present on non-primate red blood cells, and all non-immunocompromised humans have antibodies against this sugar moiety. The presence of alpha-gal antibodies in humans is a barrier against using non-primate organs for organ transplants! Paper one examines alpha-gal hypersensitivity reactions though the lens of cetuximab, and paper two tackles alpha-gal hypersensitivity reactions through the lens of the red meat allergy. Note: A fun (optional) podcast to supplement today’s class: “Alpha Gal,” Radiolab podcast, Oct. 27, 2016. Produced by Annie McEwen & Matt Kielty with reporting help from Latif Nasser. WNYC Studios.
11 | A Battle You Have Been a Part of—The Global Fight Against COVID-19 | COVID-19, caused by the SARS-CoV-2 virus, doesn’t need much introduction—COVID-19 a global pandemic we have all been living through. This week we will discuss two interesting features of COVID-19—the loss of taste/smell and the varied severity of the reactions people have to the virus. The first paper discusses how downregulation of olfactory receptors might be a mechanism by which SARS-CoV-2 causes loss of taste and smell. The second paper discusses how patients who develop neutralizing autoantibodies against interferon-ω appear to develop severe disease. We will also talk about the pros and cons of scientific research moving so quickly—why does the second paper have 107 authors? Why have more than 250 COVID-19 papers been retracted? And why does the BioRxiv preprint server (which makes papers publicly available prior to peer review) have a special note about COVID articles: “BioRxiv posts many COVID-19-related papers. A reminder: they have not been formally peer-reviewed and should not guide health-related behavior or be reported in the press as conclusive.”?
12 | What Is Your Favorite (or Least Favorite) Microbe? | You have worked hard to make it to this point in the class. Is there a topic (microbe, host defense, etc.) that you can’t get enough of? A favorite disease we have yet to explore? This week you get to choose! (We will vote during week 10 for a topic to be discussed this week.) Some potential topics are: Do vaccines cause autism (note: they do not—but we can discuss where this incorrect information comes from)? Do this year’s Nobel Prizes in Physiology or Medicine or in Chemistry relate to infectious diseases? Do antidepressants cause weight gain? (One does, and it works through the microbiome!) What are poop pills, and do they work? What are people doing about multidrug-resistant pathogens? How do some viruses cause cancer? These are just some options to consider—the world of microbes is all yours!
13 | The Final Battle—Oral Presentations | Our concluding course meeting is focused on the final oral presentations, as described in the Assignments section. In addition, we will consider what we have learned about the field of host-pathogen interactions and its future directions. Lastly, students will complete course evaluations and provide feedback about the course.

## Course Info

##### Instructor

- Dr. Lisa McLellan

##### Departments

- Biology

##### As Taught In

Fall 2022

##### Level

Undergraduate

##### Topics

- Health and Medicine
  - Immunology
- Science
  - Biology
    - Biochemistry
    - Cell Biology
    - Genetics
    - Microbiology

##### Learning Resource Types

assignment Written Assignments
assignment Presentation Assignments
co_present Instructor Insights

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