The study, led by John Whitney at the Michael G. DeGroote Institute for Infectious Disease Research, shows that the bacterial pathogen Pseudomonas aeruginosa, known to cause hospital-acquired infections such as pneumonia, secretes a toxin that has evolved to kill other types of bacteria. . For Whitney, the key aspect of his discovery is not just that this toxin kills bacteria, but how it does so.
This research is important because it shows that the toxin targets key RNA molecules of other bacteria, effectively rendering them non-functional. Like humans, bacteria need properly functioning RNA to live.”
John Whitney, Associate Professor, Department of Biochemistry and Biomedical Sciences
“It’s an all-out assault on the cell because of how many key pathways depend on functional RNAs,” said first study author Nathan Bullen, a graduate student in McMaster’s Department of Biochemistry and Biomedical Sciences. “This toxin enters its target, takes over an essential molecule needed for life, and then uses that molecule to disrupt normal processes.” Whitney and Bullen, along with colleagues at Imperial College London and the University of Manitoba, studied this toxin for nearly three years to understand exactly how it works at the molecular level. The discovery, published in Molecular Cell, was achieved by Bullen after rigorous experimentation on common toxin targets, such as proteins and DNA molecules, before finally testing the toxin against RNA. This discovery overturns established precedents created by toxins that target proteins secreted by other bacteria, such as those that cause cholera and diphtheria. The researchers say this development holds great potential for future research that could ultimately lead to new innovations that fight the bacteria that cause infection. Whitney says the newly discovered vulnerability can be exploited for future antibiotic development. Source: Journal Reference: Bullen, NP, et al. (2022) An ADP-ribosyltransferase toxin kills bacterial cells by modifying structured non-coding RNAs. Molecular Cell. doi.org/10.1016/j.molcel.2022.08.015.
