New Strategy Could Enable Existing Drugs to Kill Bacteria That Cause Chronic Infections
Source: Massachusetts Institute of Technology
Summary: Researchers have discovered a new way to make bacteria more vulnerable to a class of antibiotics known as quinolones.
Antibiotics are the prime tools in treating infectious diseases caused by bacteria but the effective therapies are limited. In the recent years, the evasion of antibiotic stress by bacteria is receiving a lot of attention by the research community. In the previous studies, the ability of antibiotics was increased by attaching a sugar molecule to the drug called as aminoglycosides to kill drug-tolerant bacteria. But aminoglycosides are not widely used because of their serious side effects. Researchers from Massachusetts Institute of Technology have discovered a new way to make bacteria more vulnerable to a class of antibiotics known as quinolones which include ciprofloxacin often used to treat infections such as Escherichia coli and Staphylococcus aureus. The study findings were published in the journal Molecular Cell.
The researchers found that, with quinolones, just adding a sugar molecule isn’t enough; they also added another molecule called as a terminal electron acceptor. Electron acceptor (usually oxygen and fumarate) plays a key role in cellular respiration (a process which bacteria uses to extract energy from sugar. Quinolones work by interfering with topoisomerases (bacterial enzymes) which help with DNA replication and repair. When tested in high-density bacterial colonies grown in a lab dish, the researchers found that quinolones along with glucose and fumarate could eliminate several types of bacteria – Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium smegmatis. They hope to test this approach with other types of antibiotics such as penicillin and ampicillin.
Prof. Karl Drlica said, “This study encourages work to find new ways to stimulate bacterial respiration and thereby enhance the production of reactive oxygen (or even non-oxygen) species during antibiotic treatment, for better eradication of bacterial pathogens, particularly those having low metabolic activity that may render them tolerant to antimicrobials.”
More Information: Arnad Gutierrez et al, “Understanding and Sensitizing Density-Dependent Persistence to Quinolone Antibiotics”, Molecular Cell (2017). DOI: dx.doi.org/10.1016/j.molcel.2017.11.012