Researchers from North Carolina State University have synthesized an analog of lipoxazolidinone A, a small molecule that is effective against drug-resistant bacteria such as MRSA. This molecule, a new synthetic compound inspired by a natural product, could be a useful chemical tool for studying other Gram-positive infections and may have implications for future drug creation.
Lipoxazolidinone A is a natural product which had been previously isolated from bacteria living in marine sediments. It is a secondary metabolite – a small molecule produced by the bacteria that isn’t key to its survival but is produced for a secondary purpose, like defense. When lipoxazolidinone A was initially isolated, researchers noted that it seemed effective against Gram-positive bacteria, like MRSA.
NC State chemist Joshua Pierce aimed to confirm those original findings and understand how the molecule’s structure correlated to its function; in short, he wanted to recreate the molecule to see what portions were directly responsible for its anti-microbial properties and then potentially improve upon that structure.
Pierce, along with current NC State graduate student Kaylib Robinson and former students Jonathan Mills and Troy Zehnder, used novel chemical tools to synthesize lipoxazolidinone A in the lab. They were able to confirm that its chemical structure matched what the initial researchers had indicated, then they worked to identify the portion of the molecule that was responsible for the activity against Gram-positive bacteria. Their result was a compound with improved potency, JJM-35.
They tested JJM-35 against a panel of resistant and non-resistant bacteria. When tested against MRSA in vitro, they found that the synthesized molecule was up to 50 times more effective than the natural product against several bacterial strains. Additionally, they found that the molecule was often more effective against resistant bacterial strains than it was against nonresistant strains.
“An exciting additional aspect of this work was that we identified that these molecules may function by inhibiting multiple biosynthetic pathways directly or indirectly,” says Pierce. “This means that bacteria may have difficulty developing resistance to potential drugs developed from these molecules.”
While more work is needed, Pierce hopes that JJM-35 and similar compounds can be used as tools to study other Gram-positive bacteria and provide a platform for the development of a novel class of anti-infective agents.
“At this point, we have a chemical scaffold – a starting piece of the puzzle. We know that this piece is effective, and so right now all efforts are focused on evaluating the properties of these molecules and their in vivo efficacy,” says Pierce. “The hope is that we can build upon this scaffold to create drugs that are effective against MRSA and other resistant bacteria at a time of dire need for antimicrobial development while also increasing the spectrum of activity.”
Receive an email update when we add a new ANTIMICROBIAL RESISTANCE article.
The Latest on: Antimicrobial development
via Google News
The Latest on: Antimicrobial development
- Active improvement of biosecurity could provide alternative to antibiotics on December 18, 2018 at 8:39 am
Antimicrobial usage in food producing animals is of major concern. A clear link between the extent of use and the development of antimicrobial resistance has already been demonstrated. To evaluate str... […]
- Domestic sales of antimicrobials for food-producing animals decline on December 18, 2018 at 7:36 am
to support the implementation of good antimicrobial stewardship practices in order to slow the development of antimicrobial resistance. Optimizing how antimicrobial drugs are used and limiting their u... […]
- OpGen Completes CDC Contract to Develop Clinical Support Mobile-Based Tools for Antimicrobial Stewardship and Infection Control on December 18, 2018 at 4:30 am
to develop smartphone-based clinical decision support solutions for antimicrobial stewardship (AMS) and infection control in low- and middle-income countries. The one-year $860,000 award began Septemb... […]
- Curetis’ Subsidiary Ares Genetics Teams Up with Leading Global Pharma Company in Fight Against Antibiotic Resistance on December 17, 2018 at 11:00 pm
“Our offerings range from data-driven approaches to antimicrobial drug development and life cycle management by Ares Genetics to customized rapid diagnostic test panels for enhanced clinical ... […]
- Global experts to address antimicrobial resistance challenge at IIT KGP on December 17, 2018 at 9:31 pm
KOLKATA: Antimicrobial resistance is one of the ... and the absence of the rapid development of antibiotic drugs. Moreover, evolution might lead to the appearance of new drug-resistant microbes ... […]
- Researchers Develop Checklist for Hospital Antimicrobial Stewardship Programs on December 17, 2018 at 7:27 am
A paper titled, "Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach," outlines the checklist development process and was publis... […]
- National Biofilms Innovation Centre award grant to Neem Biotech for novel anti-biofilm drug development on December 17, 2018 at 7:00 am
This inaugural grant has been awarded to expand the development and testing of effective anti-biofilm ... role to play in our efforts to design practical strategies to overcome antimicrobial resistanc... […]
- Global Antimicrobial Plastic Market Insights, Trends & Future Development Status Recorded during 2019-2025 on December 17, 2018 at 12:45 am
The report analyzes the current market size in terms of revenues based on the average prices of Antimicrobial Plastic products worldwide. The study also presents a 7-year outlook on the basis of antic... […]
- Global Antimicrobial Fabrics Industry Sales, Revenue, Gross Margin, Market Share, by Regions (2013-2025) on December 16, 2018 at 12:33 am
(EMAILWIRE.COM, December 16, 2018 ) Global Antimicrobial Fabrics Market report is replete with detailed analysis from a thorough research, especially on questions that border on market size, developme... […]
via Bing News