Microscopic Disease

A YSPH researcher seeks to understand the biology and transmission of different strains of bacteria.

Daniel M. Weinberger, Ph.D. investigates public health epidemics on the microscopic level. His research focus is on the biology of bacterial strains, their evolution, and which strains are most likely to be transmitted and cause diseases. Working at the intersection of microbiology and epidemiology, much of his work is focused on pneumococcus, a pathogen that is a leading cause of disease around the world. Weinberger joined the Yale School of Public Health early this year and is in the process of getting his lab established in the Department of Epidemiology of Microbial Diseases where, among other things, he will study emerging strains of bacteria and the impact of public health interventions.

Your research is described as being at the intersection of microbiology and epidemiology. What does this mean?

DW: I was originally trained as a microbiologist, and I try to apply insights from microbiology to epidemiology whenever possible. The overall goal of my work is to understand how the biology of bacterial strains influences which strains are most commonly transmitted and which are most likely to cause disease. For instance, my dissertation identified a link between the types of sugars that different bacteria produce and their ability to avoid getting killed by human immune cells. It turns out that those strains that can avoid getting killed by immune cells are also the bacteria that are most commonly transmitted among children. In this instance, we were able to draw a direct link between the basic biology of the bacteria and how frequently those bacteria are found in the population. This work had direct relevance for understanding how the bacteria would change in response to immunization.    

Much of your work focuses on the pneumococcus. Discuss the public health ramifications of this pathogen.

DW: Pneumococcus is an important cause of pneumonia, meningitis and blood-stream infection in young children and in the elderly. In the United States, we have been immunizing children with an effective vaccine for over a decade. However, the bacteria are constantly changing, so we need to be alert that new strains could emerge in the future. 

Where is it most pronounced?

DW: Pneumococcus causes a large amount of disease all over the world, including in the United States. Like many other diseases, developing countries have particularly high rates of disease. 

Who suffers the most form this infection?

DW: Young children, the elderly, people with conditions that affect the lung (such as chronic obstructive pulmonary disease), and people with conditions that affect the immune system (such as HIV/AIDS). You also tend to see particularly high rates of disease among lower-income populations and among racial/ethnic minorities. 

How does this pathogen change over time?

DW: The bacteria are constantly changing. Pneumococcus is really good at picking up pieces of DNA from the environment and adding these to its own DNA. These new pieces of DNA allow the bacteria to change in various ways—it can hide from the immune system by changing the molecules on its surface, or it can acquire the ability to resist antibiotics.

How quickly does this occur?

DW: Pneumococcus is always creating new genetic variants, so there is a large pool of strains that have differences in their DNA. As soon as you apply some pressure to the bacteria, such as antibiotics or vaccination, the bacteria can adapt very quickly.  When the pneumococcal vaccine was introduced in 2000, we saw strains increasing almost immediately that could evade the vaccine

What does this constant evolution mean for scientists and for public health?

DW: For scientists, it means that we need to understand much more about how new genetic variants are created and why some variants thrive. This evolution has many practical implications for public health. It means that antibiotic resistance can rapidly occur. And it means that strains not targeted by the vaccine might increase in the future. So far, we have been lucky that the strains not targeted by the pneumococcal vaccine are not very likely to cause disease, but more dangerous strains could potentially arise in the future.

Can these mutations be controlled or predicted?

DW: It is difficult to know exactly how the bacteria would change. In terms of vaccinations, the best we can do is to develop vaccines that target all pneumococcal strains (the current vaccines target just a handful). There are a number of vaccine candidates being developed that will be helpful here. By targeting all of the strains, we would greatly reduce the chances of having a strain emerge that could escape from the vaccine pressure. Of course, this might also raise the possibility that some other bacterial species (such as Staph) could increase when you get rid of pneumococcus.   

What is the relationship between pneumococcal disease and the flu?

DW: “The flu” is caused by a respiratory virus (influenza). People who get sick with influenza are at a higher risk for getting bacterial pneumonia within the next couple of weeks. This link has been well known for a long time—even during the great 1918 influenza pandemic, doctors recognized that many of the people who were getting really sick or dying actually had secondary bacterial infections. We have been working to understand which groups of people are most strongly at risk for secondary infections and what bacterial strains are most likely to cause these infections. We recently did a study of pneumococcal disease during the 2009 influenza pandemic and saw strong increases in pneumococcal disease among school aged children and young adults. 

You have also done work among the Navajo Indian population in Arizona? What did you find?

DW: I have been working with Kate O’Brien at Johns Hopkins, who has been collecting data on pneumococcal disease and transmission for over a decade. Like a lot of other infections, the risk for developing pneumococcal disease is much higher in the winter.  We have been using statistical models to understand the roles of bacterial transmission and viral infections in increasing the risk for pneumococcal disease.

Do you plan to study the disease in developing countries?

DW: I will be starting a project with Dr. Albert Ko and his colleagues in Salvador, Brazil, to study pneumococcal transmission and disease in the favelas (slum communities). This will be an exciting opportunity to understand pneumococcal transmission and disease in a community that is at particularly high risk for these infections.

You will soon have your own laboratory at the School of Public Health. What are your goals for the lab?

DW: The overarching goal for this work will be to apply experimental tools to questions of direct relevance for public health. We will specifically be studying bacterial strain emergence in different settings.

How did you first become interested in bacteria?

DW: I first got excited about bacteria when taking Mark Forsyth’s microbiology class as a freshman at the College of William and Mary. We learned about quorum sensing, which is a fascinating phenomenon where an individual bacterium senses how many other bacteria are nearby and adjusts its “behavior” accordingly. For example, you can grow a certain bacterial species in the lab, and when the cells reach a threshold, they start to produce a glow-in-the-dark molecule! I went on to work in Mark’s lab for three years and was hooked.

This article was submitted by Denise L Meyer on March 25, 2013.