A treatment pioneered at the University of Pittsburgh Center for Vaccine Research (CVR) is far more effective than traditional antibiotics at inhibiting the growth of drug-resistant bacteria, including so-called "superbugs" resistant to almost all existing antibiotics, which plague hospitals and nursing homes.
The findings, announced online in the journal Antimicrobial Agents and Chemotherapy and funded by the National Institutes of Health, provide a needed boost to the field of antibiotic development, which has been limited in the last four decades and outpaced by the rise of drug-resistant bacterial strains.
"Very few, if any, medical discoveries have had a larger impact on modern medicine than the discovery and development of antibiotics," said senior author Ronald C. Montelaro, Ph.D., professor and co-director of Pitt's CVR. "However, the success of these medical achievements is being threatened due to increasing frequency of antibiotic resistance. It is critical that we move forward with development of new defenses against the drug-resistant bacteria that threaten the lives of our most vulnerable patients."
Each year in the U.S., at least 2 million people are infected with drug-resistant bacteria, and at least 23,000 die as a direct result of these infections, according to the U.S. Centers for Disease Control and Prevention.
On the tail end of HIV surface protein, there is a sequence of amino acids that the virus uses to "punch into" and infect cells. Dr. Montelaro and his colleagues developed a synthetic and more efficient version of this sequence - called engineered cationic antimicrobial peptides, or "eCAPs"--that can be chemically synthesized in a laboratory setting.
The team tested the two leading eCAPs against a natural antimicrobial peptide (LL37) and a standard antibiotic (colistin), the latter being used as a last-resort antibiotic against multidrug resistant bacterial infections. The scientists performed the tests in a laboratory setting using 100 different bacterial strains isolated from the lungs of pediatric cystic fibrosis patients of Seattle Children's Hospital and 42 bacterial strains isolated from hospitalized adult patients at UPMC.
The natural human antimicrobial peptide LL37 and the colistin drug each inhibited growth of about 50 percent of the clinical isolates, indicating a high level of bacterial resistance to these drugs. In marked contrast, the two eCAPS inhibited growth in about 90 percent of the test bacterial strains.
"We were very impressed with the performance of the eCAPs when compared with some of the best existing drugs, including a natural antimicrobial peptide made by Mother Nature and an antibiotic of last resort," said Dr. Montelaro. "However, we still needed to know how long the eCAPs would be effective before the bacteria develop resistance."
The team challenged a highly infectious and pathogenic bacterium called Pseudomonas aeruginosa - which flourishes in medical equipment, such as catheters, and causes inflammation, sepsis and organ failure - with both the traditional drugs and eCAPs in the lab.
The bacterium developed resistance to the traditional drugs in as little as three days. In contrast, it took 25 to 30 days for the same bacterium to develop resistance to the eCAPs. In addition, the eCAPs worked just as effectively at killing Pseudomonas aeruginosa after it became resistant to the traditional drugs.
"We plan to continue developing the eCAPs in the lab and in animal models, with the intention of creating the least-toxic and most effective version possible so we can move them to clinical trials and help patients who have exhausted existing antibiotic options," said Dr. Montelaro.
Additional researchers on this study are Berthony Deslouches, M.D., Ph.D., Jonathan D. Steckbeck, Ph.D., M.B.A., Jodi K. Craigo, Ph.D., and Yohei Doi, M.D., all of Pitt; and Jane L. Burns, M.D., of Seattle Children's Research Institute.
This research was supported by NIH grants P30DK072506, R01AI104895, R21AI107302 and P30 DK089507, as well as funds from Pitt's Center for Vaccine Research and Cystic Fibrosis Research Center.
About the University of Pittsburgh Schools of the Health Sciences
The University of Pittsburgh Schools of the Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as the academic partner to the UPMC (University of Pittsburgh Medical Center). Together, their combined mission is to train tomorrow's health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care. Since 1998, Pitt and its affiliated university faculty have ranked among the top 10 educational institutions in grant support from the National Institutes of Health. For additional information about the Schools of the Health Sciences, please visit http://www.health.pitt.edu .
Allison Hydzik | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy