Featured Research

from universities, journals, and other organizations

New strategy in fight against infectious diseases

Date:
January 12, 2012
Source:
Ohio State University
Summary:
New research shows that infectious disease-fighting drugs could be designed to block a pathogen's entry into cells rather than to kill the bug itself. Historically, medications for infectious diseases have been designed to kill the offending pathogen. This new strategy is important, researchers say, because many parasites and bacteria can eventually mutate their way around drugs that target them, resulting in drug resistance.

New research shows that infectious disease-fighting drugs could be designed to block a pathogen's entry into cells rather than to kill the bug itself.

Historically, medications for infectious diseases have been designed to kill the offending pathogen. This new strategy is important, researchers say, because many parasites and bacteria can eventually mutate their way around drugs that target them, resulting in drug resistance.

In this study, scientists showed that using an experimental agent to block one type of an enzyme in cell cultures and mice prevented a specific parasite from entering white blood cells, a step required for the parasite to cause infection. This method applies to pathogens that must enter a host cell to survive and do their damage. Some bugs can thrive in a host body outside cell walls.

The researchers tested the experimental drug against Leishmania parasites, which are transmitted by the bite of infected sand flies. The pathogen causes a parasitic skin infection common in tropical and subtropical regions of the world, with an estimated 1.5 million new cases diagnosed each year worldwide.

"This represents a new way of thinking about treatment for infectious diseases. This was a proof of concept to see whether this emerging strategy is viable," said Abhay Satoskar, professor of pathology at Ohio State University and senior author of the study. "We aren't claiming we have a new drug for treatment. If we know this strategy works, then drugs can be developed that target different pathways in the host that could be important for pathogen invasion and survival."

The research appears online this week in the early edition of the Proceedings of the National Academy of Sciences.

Leishmania essentially hijacks a host's white blood cells to cause a skin infection called cutaneous leishmaniasis, characterized by sores of various sizes that may or may not be painful.

The standard compounds used to treat the skin disease must be injected and can cause damage to veins and a host of unpleasant symptoms. The side effects, combined with the need to receive daily shots for three weeks, lead to poor patient compliance -- which can then allow the parasites to develop resistance to the drugs.

To work around pathogens' abilities to circumvent treatment, scientists have begun developing agents that target specific elements of the infection process inside the host body. One such experimental drug is called AS-605240, and it targets one type of an enzyme that is activated when white blood cells recognize an intruder and the host body initiates an immune response.

This enzyme, PI3K gamma, controls cell movement as well as changes to a cell membrane that enable a pathogen to penetrate the cell wall. AS-605240 blocks the activity of the gamma form of the enzyme, which in turn is expected to reduce the number of cells recruited to an infection site and allow few pathogens to enter into the cells that are recruited.

Satoskar and colleagues ran a series of experiments on animal cell cultures to demonstrate that the PI3K gamma enzyme does indeed control white blood cell activity in the immune response to Leishmania mexicana infection and that the presence of the experimental agent significantly reduced the ability of the parasites to penetrate white blood cell walls. The agent also reduced the number of phagocytes -- one type of white blood cell -- that were recruited to the infection site, meaning the parasites had fewer chances to find cells that could host them.

Additionally, the researchers tested these same responses in mice, with the same results. They then compared AS-605240 treatment of Leishmania infection in mice with the current standard drug treatment, sodium stibogluconate. After two weeks of treatment of lesions on the mice, the effects of both the experimental agent and the standard treatment were very similar, and both treatments reduced the number of parasites within skin lesions when compared with untreated lesions. When the treatments were combined, the healing effects were stronger than they were in mice that received just one type of treatment.

From here, Satoskar wants to fine-tune the strategy and consider other host-based pathways that could be safely manipulated to prevent pathogens from causing infection. The findings in this work suggest that such a strategy could be used not just for treatment, but for prevention as well.

"There is no prevention for these kinds of diseases," Satoskar said. "If we had a drug that would reduce the amount of phagocytes coming to the site of infection after parasites enter the skin, that would lead to a less severe infection that the body could probably control on its own."

Some people can self-heal from a Leishmania infection, but the time it takes is unpredictable so infections are typically treated, he said.

Satoskar's research lab is supported by funding from the National Institutes of Health.


Story Source:

The above story is based on materials provided by Ohio State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. E. Cummings, J. Barbi, P. Reville, S. Oghumu, N. Zorko, A. Sarkar, T. L. Keiser, B. Lu, T. Ruckle, S. Varikuti, C. Lezama-Davila, M. D. Wewers, C. Whitacre, D. Radzioch, C. Rommel, S. Seveau, A. R. Satoskar. Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1110339109

Cite This Page:

Ohio State University. "New strategy in fight against infectious diseases." ScienceDaily. ScienceDaily, 12 January 2012. <www.sciencedaily.com/releases/2012/01/120109155731.htm>.
Ohio State University. (2012, January 12). New strategy in fight against infectious diseases. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2012/01/120109155731.htm
Ohio State University. "New strategy in fight against infectious diseases." ScienceDaily. www.sciencedaily.com/releases/2012/01/120109155731.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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