Featured Research

from universities, journals, and other organizations

Key enzyme found in disease-causing bacteria responsible for heart valve disease

Date:
March 5, 2014
Source:
Virginia Commonwealth University
Summary:
A disease-causing bacterium found in the mouth needs manganese, a trace mineral, in order to cause a serious heart infection, according to a preclinical study. Researchers have been studying the bacterium Streptococcus sanguinis to understand its role in infective endocarditis, a heart valve disease. The infection is hard to treat and can be deadly, killing more than 20 percent of the people who contract it. The findings, which may solve a longstanding mystery of why some bacteria need manganese to cause disease, provide possible new targets for antibiotics.

False-colored transmission electron micrograph of Streptococcus sanguinis cells (purple ovals) encased within an infected heart valve in an animal model of infective endocarditis. Figure courtesy of Todd Kitten, Ph.D.,/ VCU.
Credit: Figure courtesy of Todd Kitten, Ph.D.,/ VCU

A disease-causing bacterium found in the mouth needs manganese, a trace mineral, in order to cause a serious heart infection, according to a preclinical study led by researchers at Virginia Commonwealth University Philips Institute for Oral Health Research in the School of Dentistry.

Related Articles


The findings, which may solve a longstanding mystery of why some bacteria need manganese to cause disease, provide possible new targets for antibiotics.

Researchers from VCU and MIT have been studying the bacterium Streptococcus sanguinis, which lives in the mouth, to understand its role in infective endocarditis, a heart valve disease. The infection is hard to treat and can be deadly -- killing more than 20 percent of the people who contract it.

Researchers have known for some time that several types of bacteria responsible for serious infections -- including S. sanguinis -- need more manganese than others to grow normally.

In joint studies published this week in the Journal of Biological Chemistry, researchers showed that an enzyme that provides the building blocks needed for making DNA requires manganese to do its job. When the VCU team eliminated that enzyme or a second protein that attaches the manganese to the enzyme, then the bacterium could no longer cause endocarditis, nor survive within the animal model. The MIT team carefully examined the activity of the purified enzymes and determined the function of each. The VCU-MIT study is the first of its kind to test the importance of these enzymes for causing any disease.

Understanding the importance of manganese in the cell has been key to learning the best way to target the bacterium and stop it from causing disease, according to corresponding author Todd Kitten, Ph.D., associate professor at the Phillips Institute for Oral Health Research at the VCU School of Dentistry.

"The best antibiotics attack parts of a bacterium that are critical for bacterial survival, but are not found in human cells," Kitten said.

"The manganese-requiring enzyme meets both requirements because these bacteria need it to survive and humans use a very different, iron-containing enzyme to make DNA building blocks. It is the manganese requirement that makes the bacterial proteins good targets," he said.

Kitten added that humans have very little manganese in their bodies, so these bacteria require specialized systems to take in enough manganese to survive. These uptake systems are not found in humans. The team is in the early stages of a collaboration with Glen Kellogg, Ph.D., associate professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy, to create designer drugs to attack the manganese uptake system in these bacteria.

Down the road, it could be possible to target several other disease-causing bacteria that also have this enzyme and likely need it to cause disease, including MRSA; the flesh-eating bacterium, Streptococcus pyogenes; and the bacterium that causes anthrax.

The team is also examining whether manganese has other activities in these bacteria that might be equally important.

The research builds on the previously published reports of other VCU researchers. A 1995 study published in Infection and Immunity led by Francis Macrina, Ph.D., currently vice president for research at VCU, showed for the first time that a protein that turned out to be a manganese uptake protein was necessary for causing disease.

In the years since, dozens of researchers have discovered similar proteins in other disease-causing bacteria. This study also builds on work done by a collaborative VCU group that was the first to determine the DNA sequence of S. sanguinis.


Story Source:

The above story is based on materials provided by Virginia Commonwealth University. The original article was written by Sathya Achia Abraham. Note: Materials may be edited for content and length.


Journal References:

  1. D. V. Rhodes, K. E. Crump, O. Makhlynets, M. Snyder, X. Ge, P. Xu, J. Stubbe, T. Kitten. Genetic Characterization and Role in Virulence of the Ribonucleotide Reductases of Streptococcus sanguinis. Journal of Biological Chemistry, 2013; 289 (9): 6273 DOI: 10.1074/jbc.M113.533620
  2. O. Makhlynets, A. K. Boal, D. V. Rhodes, T. Kitten, A. C. Rosenzweig, J. Stubbe. Streptococcus sanguinis Class Ib Ribonucleotide Reductase: HIGH ACTIVITY WITH BOTH IRON AND MANGANESE COFACTORS AND STRUCTURAL INSIGHTS. Journal of Biological Chemistry, 2013; 289 (9): 6259 DOI: 10.1074/jbc.M113.533554

Cite This Page:

Virginia Commonwealth University. "Key enzyme found in disease-causing bacteria responsible for heart valve disease." ScienceDaily. ScienceDaily, 5 March 2014. <www.sciencedaily.com/releases/2014/03/140305125245.htm>.
Virginia Commonwealth University. (2014, March 5). Key enzyme found in disease-causing bacteria responsible for heart valve disease. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2014/03/140305125245.htm
Virginia Commonwealth University. "Key enzyme found in disease-causing bacteria responsible for heart valve disease." ScienceDaily. www.sciencedaily.com/releases/2014/03/140305125245.htm (accessed October 30, 2014).

Share This



More Plants & Animals News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Galapagos Tortoises Bounce Back, But Ecosystem Lags

Galapagos Tortoises Bounce Back, But Ecosystem Lags

Newsy (Oct. 29, 2014) The Galapagos tortoise has made a stupendous recovery from the brink of extinction to a population of more than 1,000. But it still faces threats. Video provided by Newsy
Powered by NewsLook.com
Obama: The US Will Not 'run and Hide' From Ebola

Obama: The US Will Not 'run and Hide' From Ebola

AP (Oct. 29, 2014) Surrounded by health care workers in the White House East Room, President Barack Obama said the U.S. will likely see additional Ebola cases in the weeks ahead. But he said the nation can't seal itself off in the fight against the disease. (Oct. 29) Video provided by AP
Powered by NewsLook.com
Oatmeal Healthy Recipes and Benefits

Oatmeal Healthy Recipes and Benefits

Buzz60 (Oct. 29, 2014) Oatmeal is a fantastic way to start your day. Whichever way you prepare them, oats provide your body with many health benefits. In celebration of National Oatmeal Day, Krystin Goodwin (@krystingoodwin) has a few recipe ideas, and tips on how to kickstart your day with this wholesome snack! Video provided by Buzz60
Powered by NewsLook.com
GoPro Video Gives a Lion's-Eye View of The Hunt

GoPro Video Gives a Lion's-Eye View of The Hunt

Buzz60 (Oct. 29, 2014) If you’ve ever wondered what getting takeout looks like for lions in Africa, the GoPro video from Lion Whisperer Kevin Richardson will give you a lion’s-eye view of the hunt. Jen Markham has more. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins