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
- Pharmaceutical group secures £1.8m funding on February 18, 2019 at 11:00 pm
“This is a somewhat neglected and under-invested area of antimicrobial research and so we are delighted ... NovaBiotics is a clinical-stage biotechnology company focused on the design and development ... […]
- Poultry probiotic to tackle global disease in antibiotic fight on February 18, 2019 at 4:05 pm
Dr Ron Dixon, from the School of Life Sciences at the University of Lincoln, said: "The development of antibiotics has been vital to improving human health, yet the rise of antimicrobial resistance (A... […]
- QIAGEN partners with Ares Genetics to advance global fight against antibiotic-resistant pathogens on February 18, 2019 at 1:05 pm
Antimicrobial resistance causes an estimated 700,000 deaths ... variability of operating results and allocations between customer classes; the commercial development of markets for our products to cus... […]
- Curetis’ Subsidiary Ares Genetics and QIAGEN Enter into Bioinformatics Partnership to Fight Antimicrobial Resistance on February 18, 2019 at 1:05 pm
Ares Genetics retains the rights to use ARESdb and AREStools for AMR research, customized bioinformatics services, and the development ... healthcare issue of antimicrobial resistance,” said ... […]
- Antimicrobial Susceptibility Testing Market Key Driver And Future Opportunity Assessment 2026 on February 18, 2019 at 8:52 am
Antimicrobial susceptibility testing (AST) and Antimicrobial resistance (AMR) are important criteria to be considered during the development of new antibiotics. AST aims to ensure that suitable antibi... […]
- Bringing Antimicrobial Susceptibility Testing (AST) to the Community on February 13, 2019 at 5:28 am
And from a community point of view, it will reduce the misuse and overuse antibiotics and consequently will slow down the development of new superbugs. This is only one part of the solution to antimic... […]
- Antimicrobial resistance: interventions to reduce antibiotics require tailored approach on February 11, 2019 at 7:26 pm
Published in the journal Trials and led by Dr Marco J Haenssgen, Assistant Professor in Global Sustainable Development ... the context of clinical trials in antimicrobial resistance ever conducted. […]
- Antimicrobial Prescription Self-Auditing Tool Gets Updated on February 11, 2019 at 9:53 am
FGDP(UK) also encourages general dental practitioners (GDPs) to take the British Association of Oral Surgeons’ Antimicrobial Stewardship (AMS) e-Learning Modules, which provide free verified continuin... […]
- New report gives snapshot of the antimicrobial use on farms in Ireland on February 11, 2019 at 12:20 am
This report provides for the first time a snapshot of the antimicrobial use (AMU ... from both sectors to inform future policy decisions as to how best address the development and spread of AMR.&rdquo […]
via Bing News