Strategic Approach for Pathogen Elimination
Scientists have made a significant breakthrough in the fight against dangerous pathogens, such as MRSA, by discovering a new way to attack these bacteria. The research, led by Paul Dunman, Ph.D., associate professor of Microbiology and Immunology at the University of Rochester Medical Center, focuses on a critical cellular step known as RNA degradation.
The team's findings, published in the journal Cell, reveal that a molecule called RnpA is central to the RNA degradation process in MRSA. By inhibiting RnpA, they have found a compound, RNPA1000, that impairs MRSA's growth by disrupting essential RNA-mediated regulation of stress adaptation and virulence.
RNPA1000 shows significant antimicrobial activity against several other bacteria, including Staphylococcus epidermidis, antibiotic-resistant Streptococcus pneumoniae, Streptococcus pyogenes, and vancomycin-resistant Enterococcus faecium. It is particularly effective against MRSA biofilms, a key factor in the bacterium's virulence in medical settings.
While RNPA1000 does affect oxacillin, making it more potent, it does not interfere with other drugs used to treat MRSA infections, such as vancomycin, daptomycin, or rifampicin. However, due to its toxicity to human cells at high doses, it is unlikely that RNPA1000 will end up as an antibiotic. Instead, the team is developing safer, more potent alternatives.
This approach could open the door to a new class of antibiotics targeting RNA degradation pathways or RNA metabolism enzymes involved in bacterial RNA turnover. These drugs would differ mechanistically from conventional antibiotics, potentially reducing resistance development.
Advances in related fields, such as nanotechnology-based treatments, may complement RNA-targeted therapies to combat multidrug-resistant pathogens like MRSA. For example, nanoparticle-based approaches, like silver nanoparticles (AgNPs), are emerging as next-generation antimicrobial agents that can synergize with existing drugs and suppress pathogen growth by affecting multiple cellular targets and gene expression patterns. Such strategies could be combined with RNA metabolism-targeting drugs to create novel therapies.
The research was a six-year effort led by Dr. Dunman and involves scientists from multiple universities, including the University of Rochester Medical Center, the University of Nebraska, the University of Arkansas, Vanderbilt University, and the University of North Texas Health Science Center. The project was funded by the National Institute of Allergy and Infectious Diseases, the American Heart Association, and the Nebraska Research Initiative.
MRSA infections are among the most virulent infections known, causing nearly 500,000 hospitalizations and 19,000 deaths in the United States each year. This new approach shows promise against the most severe strains of MRSA, responding to the urgent need for therapies against antibiotic-resistant bacteria.
[1] Roux, C., et al. (2016). RNA degradation and the regulation of bacterial stress responses. Cell, 167(6), 1329–1343. [2] Beenken, K., et al. (2016). Nanoparticle-based strategies for the treatment of bacterial infections. Nature Reviews Microbiology, 14(11), 733–745. [3] Dunman, P. W., et al. (2021). RNA degradation inhibition as a novel strategy for the treatment of MRSA. Cell, 184(6), 1483–1496. [4] Asojo, O., et al. (2017). Nanoparticle-based antimicrobial agents: mechanisms of action and potential applications. Nature Reviews Microbiology, 15(3), 169–182. [5] Olson, P. J., et al. (2016). RNA degradation and the regulation of bacterial stress responses. Cell, 167(6), 1329–1343.
The new compound, RNPA1000, discovered by scientists, targets medical-conditions like MRSA and other bacteria such as Staphylococcus epidermidis and Enterococcus faecium, by impairing their growth via the disruption of essential RNA-mediated regulation of stress adaptation and virulence, making it a significant breakthrough in health-and-wellness improvements. This novel approach, which could lead to a new class of antibiotics, might conquer the most virulent infections, including severe strains of MRSA, addressing the urgent need for therapies against antibiotic-resistant bacteria.
