Method for Assailing Microorganisms Innovated
A groundbreaking study led by Paul Dunman, Ph.D., Associate Professor of Microbiology and Immunology at the University of Rochester Medical Center, has revealed a promising new approach to combat methicillin-resistant Staphylococcus aureus (MRSA) and other antibiotic-resistant bacteria. The research, published in a leading scientific journal, focuses on inhibiting RNA degradation as a novel antibacterial strategy.
The team, comprising scientists from the University of Rochester, the University of Nebraska, the University of Arkansas, Vanderbilt University, and the University of North Texas Health Science Center, has identified a small molecule inhibitor, RNPA1000, that targets bacterial ribonucleases responsible for RNA degradation. By impeding the normal breakdown of RNA, RNPA1000 disrupts bacterial RNA metabolism and homeostasis, leading to growth inhibition and enhanced killing of MRSA and other bacteria, particularly within biofilms.
MRSA relies on RNA turnover for regulating gene expression, including genes essential for cell growth, survival, and antibiotic resistance. Inhibition of RNA degradation causes accumulation of defective or unnecessary RNA transcripts, leading to impaired protein synthesis and cellular stress. This results in slowed bacterial growth or bacterial cell death.
Biofilms, structured bacterial communities encased in a protective extracellular matrix, are highly resistant to antibiotics. RNPA1000’s inhibition of RNA degradation disrupts this finely tuned balance, making biofilm bacteria more susceptible to disruption and killing.
While studies focus on MRSA, bacteria generally share similar RNA degradation pathways, so RNPA1000 shows potential broad-spectrum antibacterial activity, affecting various pathogens in both planktonic (free-living) and biofilm forms. The team is now developing closely related compounds designed to be more potent than RNPA1000.
The study offers hope against severe strains of MRSA and tough infections for antibiotics to infiltrate, such as those in biofilms. MRSA infections are responsible for nearly 500,000 hospitalizations and 19,000 deaths in the United States each year.
Dunman is a leader in the development and use of array technology to study microbes and explore fresh approaches to the development of antibiotics. The team hopes that their research will open the door to an entirely new class of antibiotics. The paper is a result of a six-year effort that began when the first author, Patrick Olson, was a high school student working as an intern in Dunman's laboratory.
The groundbreaking research, focusing on health-and-wellness by combating antibiotic-resistant bacteria like MRSA, identifies a small molecule inhibitor, RNPA1000, targeting bacterial ribonucleases and inhibiting RNA degradation. This medical-condition of RNA accumulation leads to impaired protein synthesis and cellular stress, causing slowed bacterial growth or bacterial cell death, even in biofilms, offering potential broad-spectrum activity against various pathogens.
