Three antibiotics that, individually, are not effective against a drug-resistant staph infection can kill the deadly pathogen when combined as a trio, according to new research.
The researchers, at Washington University School of Medicine in St. Louis, have killed the bug -- methicillin-resistant Staphylococcus aureus (MRSA) -- in test tubes and laboratory mice, and believe the same three-drug strategy may work in people.
"MRSA infections kill 11,000 people each year in the United States, and the pathogen is considered one of the world's worst drug-resistant microbes," said principal investigator Gautam Dantas, PhD, an associate professor of pathology and immunology. "Using the drug combination to treat people has the potential to begin quickly because all three antibiotics are approved by the FDA."
The study is published online Sept. 14 in the journal Nature Chemical Biology.
The three drugs -- meropenem, piperacillin and tazobactam -- are from a class of antibiotics called beta-lactams that has not been effective against MRSA for decades.
Working with collaborators in the microbiology laboratory at Barnes-Jewish Hospital? in St. Louis, Dantas' team tested and genetically analyzed 73 different variants of the MRSA microbe to represent a range of hospital-acquired and community-acquired forms of the pathogen. The researchers treated the various MRSA bugs with the three-drug combination and found that the treatments worked in every case.
Then, in experiments conducted by collaborators at the University of Notre Dame, the team found that the drug combination cured MRSA-infected mice and was as effective against the pathogen as one of the strongest antibiotics on the market.
"Without treatment, these MRSA-infected mice tend to live less than a day, but the three-drug combination cured the mice," Dantas said. "After the treatment, the mice were thriving."
Dantas explained that the drugs, which attack the cell wall of bacteria, work in a synergistic manner, meaning they are more effective combined than each alone.
The researchers also found that the drugs didn't produce resistance in MRSA bacteria -- an important finding since more and more bacteria are developing resistance to available drugs.
"This three-drug combination appears to prevent MRSA from becoming resistant to it," Dantas said. "We know all bacteria eventually develop resistance to antibiotics, but this trio buys us some time, potentially a significant amount of time."
Dantas' team also is investigating other antibiotics thought to be ineffective against various bacterial pathogens to see if they, too, may work if used in combination with other drugs.
"We started with MRSA because it's such a difficult bug to treat," he said. "But we are optimistic the same type of approach may work against other deadly pathogens, such as Pseudomonas and certain virulent forms of E. coli."
Funding for this research comes from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of General Medical Sciences, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH). Additional funding comes from an NIH Director's New Innovator Award and a Ruth Kirschstein National Research Service Award from NIH. Grant numbers are DP2 DK098089, R01 GM099538, AI90818, AI104987, GM007067, T32 GM075762, F31 AI115851.
Gonzales PR, Pesesky MW, Bouley R, Ballard A, Biddy BA, Suckow MA, Wolter WR, Schroeder VA, Burnham C-AD, Mobashery S, Chang M, Dantas G. Synergistic, collaterally sensitive ß-lactam combinations suppress resistance in MRSA. Nature Chemical Biology, published online Sept 14, 2015.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Jim Dryden | EurekAlert!
New flexible, transparent, wearable biopatch, improves cellular observation, drug delivery
12.11.2018 | Purdue University
Exosomes 'swarm' to protect against bacteria inhaled through the nose
12.11.2018 | Massachusetts Eye and Ear Infirmary
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.
Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
12.11.2018 | Life Sciences
12.11.2018 | Materials Sciences
12.11.2018 | Physics and Astronomy