Finding the perfect match: New approach to battle drug-resistant bacteria

Antibiotics were the wonder drug of the 20th century, but persistent use and over-prescription have opened the door that has allowed bacteria to evolve resistance. According to the Centers for Disease Control and Prevention, more than two million people in the United States develop bacterial infections that are resistant to multiple antibiotics every year.

Previous research has shown that pairing antibiotics can be more effective than using single drugs, but finding these perfect matches has proven elusive. Researchers at University of Utah Health have developed a rapid screening method to identify beneficial pairs of existing FDA-approved drugs to combat multi-drug resistant (MDR) bacterial infections. The results are published online in PLoS Biology.

"By pairing FDA-approved drugs synergistically, we have the potential to take these pairs to clinic much more quickly than new drugs, which can be expensive and time intensive to create and approve," Jessica Brown, Ph.D., assistant professor in pathology at U of U Health.

Brown and her team analyzed a bacterial dataset consisting of 4,000 E. coli mutants grown in the presence of 100 FDA-approved drugs. Each mutant is missing a specific gene and interacts with each drug in a specific way, producing a unique chemical genetic signature.

Brown poured through the chemical genetic signature dataset to identify genes that could convey weakness in bacteria and offer new opportunities to pair different drugs to combat these difficult infections.

A synergistic pairing is more powerful than just adding two drugs together. It amplifies each drug's effectiveness by at least four-fold, according to Brown.

The approach identified 14 drugs that could be paired synergistically.

The most promising synergistic pairing in this study combined azidothymidine (AZT), one of the earliest drugs prescribed to treat HIV-AIDS, with floxuridine, a cancer drug with a similar chemical genetic signature as a commonly prescribed antibiotic ¾ trimethoprim.

Brown tested the effectiveness of the floxuridine and AZT pair by treating zebrafish infected with trimethoprim-resistant E. coli. The synergistic drug pair reduced the bacterial load by 10,000-fold compared to treating with the traditional antibiotic pair of trimethoprim and sulfamethizole.

"We were surprised to see how well the floxuridine and AZT treatment worked," said Morgan Wambaugh, Ph.D. Candidate working with Brown. "To evaluate the effectiveness of a treatment, we typically dilute a sample to count the remaining bacteria, only to discover they were mostly all gone."

Brown explains the power behind this particular drug pair. AZT blocks DNA replication, while floxuridine, like the antibiotic trimethoprim, prevent bacteria from repairing their DNA. While many bacteria have developed resistance to trimethoprim, floxuridine remains effective, even against trimethoprim-resistant bacteria, because it works by another mechanism.

Several of the drugs identified in this study are not currently used as antibiotics, but produce an effective response against MDR bacteria.

"The reuse of FDA-approved drugs can speed up the regulatory process, because the drugs are already approved for use in humans," said Brown. "This approach could open up new lines of research for future drug development that could enhance current antibiotic treatments," continued Wambaugh.

This approach is rapid. Brown believes it would only take a few months to screen a wider net of FDA-approved drugs for additional synergistic pairs.

"Once we understand the mechanism of how each drug works, we can design new pairs to combat resistance," said Brown.

The synergistic drug pairing also has the potential to slow the evolution of resistance to the drug therapies, although this was not directly explored in this study.

"We're excited to expand this work to other antibiotics and infectious diseases," Brown said. "We hope that this will make our new treatments broadly accessible to patients in the U.S. and internationally."

For the next step, Brown wants to collaborate with a clinician to take some of the identified drug pairs into clinical trials to examine their effectiveness at combating difficult bacterial infections in people.

Credit:
ScienceDaily

Comments

Post a Comment

Popular posts from this blog

NEEM TREE & MEDICINAL USES

Image
NEEM TREE & MEDICINAL USES "Dogo Yarow" The TREE of LIFE The Magical Evergreen Tree The neem plant is native to India but gradually spread to many parts of the world over the years. IT HAS BEEN USED LOCALLY AS MEDICINE OVER THOUSANDS OF YEARS, AND OVER THE CENTURIES IN PHARMACEUTICALS, COSMETICS AND TOILETRIES. Almost every part of this wonder plant is Medicinal, ranging from roots, bark, twigs, leaves, flowers and seeds...... It's very common within the Hausa communities in Cameroon more especially in the Northen regions which predominantly occupied by the Hausa ethnic group. They call it Dogo Yarow which when translated means, TALL CHILD or TALL PIKIN in Pidgin English..... MEDICINAL USES OF THE TREE OF LIFE - NEEM: * Cardiac Problems: Infusions of leaves in HOT water when taken removes bad sugars and toxins from blood, dilates blood vessels, improves blood circulation and balances heart pumping rates * High Blood Pressure: It relaxes erratic heart beats a
Read more

TAPE WORMS: Unwanted 'Guests' in the Intestines

Image
https://m.facebook.com/story.php?story_fbid=261432537653223&id=193799827749828 Tapeworms are flat, segmented worms that live in the intestines of some animals. Animals can become infected with these parasites when grazing in pastures or drinking contaminated water. Eating undercooked meat from infected animals is the main cause of tapeworm infection in people. Although tapeworms in humans usually cause few symptoms and are easily treated, they can sometimes cause serious, life-threatening problems. That's why it's important to recognize the symptoms and know how to protect yourself and your family. Tapeworm Causes Six types of tapeworms are known to infect people. They are usually identified by the animals they come from -- for example, Taenia saginata from beef, Taenia solium from pork, and Diphyllobothrium latum from fish. Tapeworms have a three-stage lifecycle: egg, an immature stage called a larva, and an adult stage at which the worm can produce more eggs. Bec
Read more

8,260 students graduate as ABU holds 40th convocation tomorrow

Image
The 40th convocation ceremony of the Ahmadu Bello University (ABU), Zaria will hold tomorrow with 8,260 students graduating with first degrees. The Vice Chancellor of the university, Professor Ibrahim Garba, made this known during a press briefing yesterday, saying that the convocation would confirm the graduation of 256 PhD students. He said the number of PhD and about 3,600 other postgraduate graduands was a confirmation of the new status that ABU had assumed where priority was given to postgraduate studies. Professor Garba said ABU was expanding its carrying capacity through introduction of new programmes to accommodate more applicants who usually overwhelmed the school. “It is in this direction that we now allow more institutions to run degree programmes with our affiliation.  We have also introduced distance learning where we admit hundreds of students and we would commence undergraduate studies in the centre,” he said.
Read more