College of Graduate Studies

UT researchers take new approach in cholera prevention by Cara Deangelis, PhD student in the Department of Medical Microbiology and Immunology UT

    DeAngelis

    Cara DeAngelis is a PhD student of microbiology and immunology in the University of Toledo College of Medicine.

How often do you find yourself thinking about the safety of the water you drink?

Perhaps you thought about it during the summer of 2014 when the southwest region of Lake Erie had a toxic algae bloom. After that summer though, I am sure many of us returned to using our tap water, without any second thoughts.

Cholera

Cholera is commonplace in countries where access to clean water is limited. As many as 143,000 deaths from the disease occur annually. UNIVERSITY OF TOLEDO

Unfortunately, many countries lack the basic resources that we take for granted every day, like clean drinking water. Those without water treatment plants and sewage systems are at risk for numerous diseases. One such disease is cholera, caused by the bacteria Vibrio cholerae.

Vibrio cholerae likes to live in warm, salty waters and can attach to shellfish. If you drink water or eat food contaminated with these bacteria, you can become infected and very sick within a few hours. The bacteria secrete a toxic substance, called cholera toxin, in the intestine of an infected person. The toxin causes a very rapid loss of water, leading to severe dehydration and death if not treated.

The best treatment for cholera is oral rehydration therapy, which replaces the water lost from the body. Such resources are not always available or easily accessible in countries affected by this disease, so other treatments are being investigated.

Luckily for us, cholera is not a problem in industrialized countries like the United States. However, Vibrio cholerae affects more than 50 countries worldwide, causing about 4 million cases of cholera a year and up to 143,000 deaths. Therefore, this disease is a global threat to public health and research is necessary to help save lives.

At the University of Toledo College of Medicine and Life Sciences, formerly the Medical College of Ohio, I am a part of Jyl Matson’s research group that studies Vibrio cholerae. The bacteria has an outer and an inner membrane, which protect them from their environment, whether that is water or the human intestine. For example, these bacteria have to be able to live through large changes in temperature, the acid in our stomachs, and attack from our immune systems.

DeAngelis

Cara DeAngelis is a PhD student of microbiology and immunology in the University of Toledo College of Medicine.

Picture these bacteria as tiny castles surrounded by two outer walls for defense against outside enemies. If cannons are fired at either wall, soldiers are sent to shield the weak locations and keep out the enemy.

My project in Ms. Matson’s laboratory is focused on learning about a system that the bacteria deploy when their inner membrane is damaged. This response system is called the phage-shock-protein response and has never been studied in Vibrio cholerae. However, it has been studied in several other types of bacteria, which give us clues about what it could do in Vibrio cholerae. We know that in those bacteria, when the inner membrane is damaged, the bacteria turn on their phage-shock-protein response. The bacteria then make specific proteins that are sent to the inner membrane to keep it functioning correctly. This response system makes these other bacteria better at causing disease.

It is likely that the phage-shock-protein response in Vibrio cholerae operates in a similar manner as these other bacteria, but it is also possible that it works in a different way. My research is to figure out exactly what this phage-shock protein response is doing in Vibrio cholerae.

One way I have begun to study this response system is by deleting specific pieces of DNA, or genes, that create phage-shock proteins. The concept behind this is elegantly simple: If we remove a gene from the bacteria and they do not function as well without it in stressful situations, then we know that it was important for the bacteria to survive. So far, I have found that all of the phage-shock-protein genes I have deleted are important for the bacteria to survive in stressful environments.

The next step is to target the proteins made from these genes to cripple the bacterial response system. You would expect that the bacteria would be weaker and therefore more easily defeated without that protection system in place, would you not? This would be like removing the soldiers that help protect the castle wall.

By understanding the phage-shock-protein response in further detail, we hope to contribute to the development of more effective treatments for cholera. If we manage to target and knock down the phage-shock-protein response, other medications might be better able to kill the bacteria. With those two methods of attack combined, we may be able to decrease the number of lives lost to cholera.

Cara DeAngelis is a PhD student in the Department of Medical Microbiology and Immunology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Ms. DeAngelis is doing her research in the laboratory of Jyl Matson. For more information, contact Cara.Deangelis@rockets.utoledo.edu or go to utoledo.edu/​med/​grad/​biomedical.


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