3 The Friday Four

In this edition of the Friday Four: how llamas are helping the fight against C. Diff infection, a new strategy to reduce antibiotic-resistant infections, how antibiotics may make fighting the flu harder,  a chart on US Gov't R & D funding for 2011 - plus two bonus links.

(And apologies for the island time posting - still Friday here, but not much longer.)


1) Researchers step closer to treatment of virulent hospital infection: Unique antibody from llama provides weapon against Clostridium difficile

Llamas

Researchers from the University of Calgary, Canada discovered that a simple antibody found in llamas may be the answer for future drug development against C. difficile. C. difficile is becoming increasingly resistant to existing antibiotic treatment such as metronidazole and vancomycin.

Llamas have antibodies which are very similar to human antibodies, and also another class of antibodies which are about 1/10th the size of human antibodies and are easier to engineer into drugs.

These antibodies - known as single-domain antibodies - bind to the C. difficile toxins with high affinity and interfere with the toxins' ability to damage cells.

Dr. Jamshid Tanha, the corresponding author of the study from the National Research Council in Ottawa says that understanding how camelid antibodies work will ultimately allow researchers to develop a new treatment for this important disease and potentially others.

"We are currently working with Dr. Ng's group to determine why these antibodies are successful," says Tanha.

Comment: Research in this field is especially important to patients who use high doses or long courses of antibiotics and run the risk of infection with C. difficile. Next to antibiotic resistance, C. difficile infection is one of the biggest problems with long-term antibiotic use, whether administration is oral or intravenous.

Original Source Publication:
The article, Neutralization of Clostridium difficile toxin A with single-domain antibodies targeting the cell-receptor binding domain, is published in the Journal of Biological Chemistry http://www.jbc.org/ and written by Greg Hussack (NRC and University of Ottawa), Mehdi Arbabi-Ghahroudi (NRC and Carleton University), Henk van Faassen (NRC), Glen Songer (University of Arizona), Kenneth K.-S Ng (Alberta Ingenuity Centre for Carbohydrate Science, and University of Calgary), Roger MacKenzie (NRC and University of Guelph), Jamshid Tanhan (NRC, University of Ottawa and University of Guelph).

2) Economics and Evolution Help Scientists Identify New Strategy to Control Antibiotic Resistance

Pseudomonas aeruginosa

In the March 2011 issue of Genetics, the scientists show that bacterial gene mutations that lead to drug resistance come at a biological cost not borne by nonresistant strains. They speculate that by altering the bacterial environment in such a way to make these costs too great to bear, drug-resistant strains would eventually be unable to compete.

A team of scientists from the University of Oxford, U.K. have taken lessons from Adam Smith and Charles Darwin to devise a new strategy that could one day slow, possibly even prevent, the spread of drug-resistant bacteria.

"Our study shows that concepts and tools from evolutionary biology and genetics can give us a boost in this area by identifying novel ways to control the spread of resistance," said Alex Hall, PhD, researcher from the Department of Zoology at the University of Oxford.

The research team measured the growth rates of resistant and susceptible Pseudomonas aeruginosa bacteria in a wide range of laboratory conditions. They found that the cost of antibiotic resistance has a cost to bacteria, and can be eliminated by adding chemical inhibitors of the enzyme responsible for resistance to the drug. Manipulating the cost of resistance may make it possible to prevent resistant bacteria from persisting after the conclusion of antibiotic treatment.

Comment: As the IDSA is moving to tighten the use of antibiotics in the US (and possibly worldwide) in order to prevent growing antibiotic resistance, it's important to research how to inhibit resistance. Research such as this could allow hospitals to continue to prescribe antibiotics with less concern about resistance to potentially deadly infections such as MRSA. It will also help in the fight against various tickborne infections.

Original Source Publication:
A. R. Hall, J. C. Iles, R. C. MacLean. The Fitness Cost of Rifampicin Resistance in Pseudomonas aeruginosa Depends on Demand for RNA Polymerase. Genetics, 2011; 187 (3): 817 DOI: 10.1534/genetics.110.124628

3) Antibiotics may make fighting the flu harder

H1N1 flu virus

Scientists knew that friendly bacteria in the intestines could help stop disease-causing bacteria from setting up shop in the gut. And this is one of the reasons Lyme disease patients take lots of probiotics between antibiotic doses - to prevent disease-causing bacteria such as C. difficile from setting up shop and producing toxins.

Some previous experiments hinted that gut microbes could influence how well the immune system works, but researchers thought the effect was mainly confined to the digestive system. Now there's evidence that friendly, or “commensal,” bacteria help defend against viruses affecting other parts of the body by keeping the immune system on alert for viral invaders, a research team discovered.

“What’s fascinating about this [new study] is that there’s a distant regulation of resistance to viruses by gut microbiota,” says Alexander Chervonsky, an immunologist at the University of Chicago.

Researchers found that the presence of "friendly" bacteria helped fight off viral infections that could affect the lungs - something that came as a total surprise.

Antibiotic treatment impaired the mice’s ability to make an important flu-fighting molecule called interleukin-1 beta or IL-1 beta, which is necessary to combat influenza and other viruses. Gut bacteria are constantly priming the immune system to make IL-1 beta, keeping the immune system vigilant against flu and other viruses. The researchers aren’t sure yet which bacteria in the gut are responsible for the virus-defense mechanism, but they are looking at Lactobacillus as a potential candidate for study.

Comment: Here is more evidence that keeping one's gut and intestinal flora in balance is important to one's overall immune system. Patients who are taking antibiotics are encouraged to keep up their probiotics to maintain a healthier balance, and more research is needed to find out which commensal bacteria are the most beneficial for combatting both bad bacterial and viral infections.


Original Source Publication:
T. Ichinohe, et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proceedings of the National Academy of Sciences. Published online ahead of print, March 2011.

4) Not so much a link, but something to think about: Where US Gov't R & D Funding Is Spent...


Source:LiveScience

Comment: So $32.09 billion goes to the NIH, and everything else gets a smaller slice of the research pie.  Why is that? And are contracts in other areas that are awarded potentially falling under that mysterious "All Other" slice of the pie?

Bonus links for today: The Daily Kos Series on Lyme Disease Awareness 2010 raised the issue of Chronic Lyme disease and March 10, 2011's Chronic Tonic Column focused on one person's Lyme disease experience.

It's interesting to see people writing about Lyme disease at The Daily Kos - not your typical Lyme disease discussion venue. I don't know when or if to expect any Lyme Disease Awareness posts for this May, but I plan to check out the site then and see if there are new ones.