Shannon Manning: Decoding deadly E. coli
Jan. 7, 2015
Shannon Manning is an AgBioResearch microbiologist and molecular geneticist. Her research focuses on applying molecular and evolutionary approaches to study the virulence, epidemiology and evolution of bacterial pathogens to better understand pathogenesis, emergence, and transmission in human and animal populations.
In my lifetime, I have observed the emergence of multiple pathogens that were previously not known to affect humans. Some examples include human immunodeficiency virus (HIV), ebola, West Nile virus, Lyme disease and two unique types of Escherichia coli.
I have also witnessed the re-emergence of known pathogens with new traits such as the ability to resist antibiotics as in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA).
Although reports about the diseases caused by these pathogens can be frightening, I have always been interested in figuring out why and how they initially emerge. I am thrilled to be asking these types of research questions at Michigan State University.
After I earned my undergraduate degree, I worked in a lab that studied microbial evolution. We documented genetic changes in E. coli over time to better understand how bacteria adapt to specific environmental conditions. I was fascinated to learn that small mutations could result in physical and biochemical changes that could alter its ability to survive. It was then that I recognized that this concept was also critical for the emergence of new pathogens and that my primary interests involved better understanding this process.
Consequently, I earned a master’s degree in public health and Ph.D. in molecular epidemiology and was selected to be an emerging infectious disease research fellow with the Centers for Disease Control and Prevention. I was stationed at the Michigan Department of Community Health and my project involved setting up a statewide surveillance system to identify E. coli O157, which emerged in a 1982 outbreak and currently causes up to 196,000 infections in the U.S. each year.
Notably, the emergence of E. coli O157 was linked to the acquisition of genes that allowed the bacterium to produce the potent Shiga toxin. This alteration of the E. coli chromosome instantaneously turned a common E. coli strain into a pathogen capable of infecting humans. This genetic alteration is critical for the emergence of new E. coli pathogens and represents the focus of several of my current studies.
In 2011, I was given the opportunity to work with a new E. coli pathogen that emerged in Germany and caused about 3,500 cases and 54 deaths, and thus, represents the deadliest E. coli outbreak to date.
The outbreak was caused by E. coli (O104:H4), which represents a hybrid of two E. coli types that had acquired the genes for Shiga toxin production and antibiotic resistance. The question that remained unanswered, however, was ‘why the E. coli O104:H4 outbreak strain caused more severe disease and death than E. coli O157 outbreaks.’
We demonstrated that it makes a strong biofilm, a densely packed cluster of bacterial cells encased in a self-produced, protective matrix, and that cells within a biofilm had a higher than normal level of toxin production resulting in more damage to the kidneys.
Some of my current work involving the E. coli O104:H4 outbreak strain focuses on its evolution and defining ways to block biofilm formation. We have also screened for the bacterium in cattle, which are an important source of pathogenic E. coli. Through this study, we have identified numerous types of E. coli that have not been previously implicated in human infections, but all have acquired the ability to produce the Shiga toxin.
Unfortunately, we can’t predict whether some of these new E. coli strains will result in a future outbreak, or whether future E. coli O104:H4 outbreaks will arise. We can, however, do our best to understand the pathogens that we have identified and evaluate whether they have the ability to cause disease.
The tricky part is determining which bacterial features are critical for this process. Although the Shiga toxin is important, these pathogens also have factors that help them pass through the highly acidic stomach, attach to the intestinal tissue, avoid killing by immune cells, acquire nutrients and proliferate.
Determining which bacterial features are most important for disease will help identify ways to block them via vaccines or therapeutics. It is my hope that some of my research findings will impact future prevention practices and ultimately reduce the number of people affected by these bacterial infections.