Featured Research

from universities, journals, and other organizations

Pathogen's scissor-like enzyme provides new clues to treatment of infectious disease

Date:
April 4, 2013
Source:
UT Southwestern Medical Center
Summary:
Researchers report that a pathogen annually blamed for an estimated 90 million cases of food-borne illness defeats a host's immune response by using a fat-snipping enzyme to cut off cellular communication.

Along with Dr. Neal Alto is Nikolay Burnaevskiy, a graduate student in microbiology.
Credit: UT Southwestern Medical Center

UT Southwestern Medical Center researchers report that a pathogen annually blamed for an estimated 90 million cases of food-borne illness defeats a host's immune response by using a fat-snipping enzyme to cut off cellular communication.

"Our findings provide insight into severe bacterial infectious diseases, as well as some forms of cancer, in which the attachment of fat molecules to proteins is an essential feature of the disease process," said Dr. Neal Alto, assistant professor of microbiology and senior author of the study in today's print edition of Nature. The study's first author is Nikolay Burnaevskiy, a graduate student in microbiology.

The research group discovered a scissor-like enzyme that specifically cuts off functionally-essential fatty acids from proteins. "The one we studied in particular -- a 14-carbon saturated fatty acid called myristic acid- has received a lot of attention due to its crucial role in the transformation of normal cells to cancer cells and for promoting cancer cell growth," Dr. Alto said.

Because of the fat's importance in human disease, researchers have tried for years to identify effective methods to remove them from proteins. "To our amazement, bacteria have invented the precise tool for the job," Dr Alto said.

The bacteria used in this study, Shigella flexneri, are able to cross the intestinal wall and infect immune cells. Other intestinal bacteria, such as E. coli, are unable to do this. Once Shigella encounters immune system cells, including white blood cells such as macrophages, the bacteria use a needle-like complex to inject the cells with about 20 bacterial toxins.

The UTSW researchers conducted a series of experiments to characterize one of those toxins, called IpaJ, chosen in part because so little was known about the protein. They not only discovered IpaJ's fat-cutting ability, but also determined how the protein disables the immune system's communication infrastructure, which Dr. Alto compared to knocking out a bridge needed to deliver a package.

"Normally, a macrophage will engulf an invading bacteria and send out cytokines, proteins that act as cellular alert signals, which in turn recruit more immune cells to the site of infection," Dr. Alto said. "When the macrophages engulf Shigella, however, the bacteria use IpaJ to cut fatty acids from proteins, which need those fats attached in order to sound the alarm. Doing so buys more time for the bacteria to grow and survive.

"It's very interesting from a disease process point of view, but it's also important because we now have a potential drug target," said Dr. Alto. The next step, he said, will be to identify small molecule inhibitors that are specific to this fat-snipping protease and that might be developed into drugs.

The study in Nature received support from the National Institutes of Health, the Welch Foundation, and the Burroughs Wellcome Fund.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nikolay Burnaevskiy, Thomas G. Fox, Daniel A. Plymire, James M. Ertelt, Bethany A. Weigele, Andrey S. Selyunin, Sing Sing Way, Steven M. Patrie, Neal M. Alto. Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ. Nature, 2013; 496 (7443): 106 DOI: 10.1038/nature12004

Cite This Page:

UT Southwestern Medical Center. "Pathogen's scissor-like enzyme provides new clues to treatment of infectious disease." ScienceDaily. ScienceDaily, 4 April 2013. <www.sciencedaily.com/releases/2013/04/130404092825.htm>.
UT Southwestern Medical Center. (2013, April 4). Pathogen's scissor-like enzyme provides new clues to treatment of infectious disease. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2013/04/130404092825.htm
UT Southwestern Medical Center. "Pathogen's scissor-like enzyme provides new clues to treatment of infectious disease." ScienceDaily. www.sciencedaily.com/releases/2013/04/130404092825.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Uganda on Alert for Ebola but No Confirmed Cases

Uganda on Alert for Ebola but No Confirmed Cases

AFP (July 31, 2014) Uganda's health minister said on Thursday that there are no confirmed cases of Ebola in the country, but that it remained on alert for cases of the deadly virus. Uganda has suffered Ebola outbreaks in the past, most recently in 2012. Duration: 00:59 Video provided by AFP
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:
from the past week

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