Quest for new antibiotics leads to novel sources

[Source: Susan J. Landers, AMNews] - Washington -- As bacteria become resistant to increasing numbers of antibiotics the search is on for new and effective antimicrobials. Researchers are hunting near and far -- on the ground and even in the swamps.

For instance, the minerals from certain clays, which have been used medicinally for thousands of years, could form the basis of a new generation of inexpensive antibiotics, researchers from Arizona State University reported at the national meeting of the American Chemical Society in New Orleans, April 6-10.

And proteins found in alligator blood are being eyed as powerful new medications that could help fight infections associated with diabetic ulcers, severe burns and the "superbugs" that are raising fears in the medical community. The alligator study was also presented at the chemical society's meeting.

The list of diseases that are becoming more difficult to fight with first-line antibiotics is growing longer. Included are tuberculosis, staph and strep infections, malaria, head lice and, recently, meningococcal disease. Methicillin-resistant Staphylococcus aureus, or MRSA, is particularly notorious for making the jump from a hospital problem to one that causes illness and deaths in communities.
This dangerous trend has prompted efforts by public health and medical societies, including the AMA, to educate physicians about the importance of appropriately prescribing antibiotics and the need to inform patients about the dangers of antimicrobial resistance.

Thinking outside the box

The importance of the quest for new medications has sparked interest in the healing powers of clay. "The catch word is MRSA," said Shelley Haydel, PhD, assistant professor in the School of Life Sciences and the Biodesign Institute at Arizona State University in Tempe. "We've shown in the laboratory that [some clay] does have some effectiveness at killing MRSA."

Clay's power was a surprise to Dr. Haydel. "When I first got involved, I looked at it with a skeptical eye," she said. But when a paste of clay killed bacteria in 12 hours, she was hooked. Dr. Haydel and her colleagues have screened about 30 different clays -- samples from all over the world -- and found three with antimicrobial properties.

Some clay has antimicrobial properties.

Dr. Haydel isn't sure what the medical community's response will be to this unorthodox approach. "We have to show that it is safe -- and we believe that it is safe because it's been used for so long -- and effective at getting rid of infections in test subjects.

"If we don't have to know exactly how it is working and just show that it is working and not causing additional harm, we may be a couple of years away from clinical use."
Meanwhile, Mark Merchant, PhD, assistant professor of biochemistry at McNeese State University in Lake Charles, La., is wrestling alligators in the pursuit for a new antibiotic. After subduing a gator he extracts blood.

Previous studies by Dr. Merchant showed that alligators have unusually strong immune systems that can fight fungi, viruses and bacteria without having prior exposure to them. Scientists believe this is an evolutionary adaptation to promote quick wound healing, as alligators are often injured during territorial battles in the unhygienic world they inhabit.

Dr. Merchant and colleagues have already isolated white blood cells and extracted the active proteins.

"We're very excited about the potential of these alligator blood proteins as both antibacterial and antifungal agents," he said. "There is a real possibility that you could be treated with an alligator blood product one day." However, that day is not likely to arrive for seven to 10 years.

In another development, the Food and Drug Administration approved a test April 3 that allows rapid screening for MRSA. The nasal test, which will provide results within 24 hours according to the manufacturer, improves on the two-day wait that had been necessary previously.

UCLA/VA partners with ASU to advance biosensor technology for urinary tract infections

[Source: Eureka Alert] -- NIH award will help team develop a faster, more sensitive product to test for infection. Researchers from the David Geffen School of Medicine at UCLA, the Veterans Affairs Greater Los Angeles Healthcare System, GeneFluidics Inc. and the Biodesign Institute at Arizona State University have received a five-year, $3.2 million award from the National Institutes of Health to help rapidly diagnose and treat urinary tract infections — the most common cause of hospital-associated infection in the United States. The initiative brings together academic and industry leaders to further advance a groundbreaking technology — initially developed by UCLA/VA researchers and corporate partner GeneFluidics — that allows for rapid, species-specific detection of bacteria in human clinical fluid samples using a microfabricated electrochemical sensor array.

Joe Wang, director of the Biodesign Institute’s Center for Bioelectronics and Biosensors, will join the collaboration to improve the performance of the test by dramatically enhancing its sensitivity and speed. Wang has more than 25 years of success in biomedical applications and a strong track record of bringing similar sensors, used for glucose monitoring, to the market. “We are extremely fortunate to have Joe Wang and the Biodesign Institute as partners in this endeavor,” said principal investigator Dr. David Haake, professor of medicine at UCLA and an infectious diseases specialist at the VA. “Biodesign’s expertise will make it possible to quickly bring the electrochemical sensor to clinical reality. Working together, we hope to fundamentally change the way antibiotics are selected for the treatment of infectious diseases.”

“The goal of our collaborative effort is to develop all of the technical components to produce a biosensor that can rapidly and reliably identify a bacteria and its spectrum of antibiotic susceptibility to aid point-of-care diagnostics for the clinic,” Wang said.

Industrial partner GeneFluidics will help deliver a custom-built, fully functional prototype, called PATHOSENSE, within the time frame of the grant. At the conclusion of the grant period, the team hopes to work with GeneFluidics for near-term deployment of the PATHOSENSE instrument in multicenter clinical testing. “By combining our expertise, we will be able to bring outstanding pathogen screening products to health care professionals,” said Dr. Vincent Gau, president of GeneFluidics. “Using GeneFluidics’ proprietary electrochemical platform as the backbone of our tests allows for very high sensitivity and for a streamlined system that delivers antibiotics resistance results in record time — two hours instead of two-to-three days.”

The technology relies on the ability to detect the genetic signature of a bacterial pathogen. The researchers will use 16S rRNA, a ribosomal molecule found in all bacteria, to identify the bacteria species. The research team will focus on enhancing the performance and validation of the electrochemical biosensor assay and will develop an antimicrobial susceptibility test to rapidly select the best antibiotic for treatment. “Our mission is to create a new technology to solve an old problem, which is the diagnosis of urinary tract infections — the second most common bacterial infection — in a clinically relevant time frame,” said Dr. Bernard Churchill, chief of pediatric urology at the Clark-Morrison Children’s Urological Center at UCLA.

In current laboratory practice, pathogens in urine specimens are grown in culture dishes until they can be visually identified. The major drawback of this century-old technique is the two-day time lag between specimen collection and bacteria identification. As a result, physicians must decide whether to prescribe antibiotic therapy and, if so, which antibiotic to use — all without knowing the actual cause of the infection, if any. In contrast, the new biosensor technology would allow physicians to prescribe targeted treatment without the wait.

Urinary tract infection is the most common urological disease in the United States and the most common bacterial infection of any organ system. It is a major cause of patient death and health care expenditures for all age groups, accounting for more than 7 million office visits and more than 1 million hospital admissions per year. Catheter associated urinary tract infection accounts for 40 percent of all hospital-acquired infections — more than 1 million cases each year. The total cost of urinary tract infections to the U.S. health care system in 2000 was approximately $3.5 billion. The grant is funded by the National Institute of Allergy and Infectious Diseases, a branch of the National Institutes of Health.