New research from scientists at the University of Sheffield and elsewhere shows that methicillin resistant staphylococcus aureus (MRSA) relies on two co-dependent mechanisms to survive exposure to high-level antibiotics. Their findings could pave the way to new approaches for controlling infections caused by the superbug. Full details of the study are published in a Science paper titled, “Two codependent routes lead to high-level MRSA.”
Previous studies have demonstrated that in order to be resistant, MRSA acquires a new cell wall enzyme that allows it to survive exposure to antibiotics. The Sheffield researchers found that this alone is insufficient for survival. Digging into the details, they found evidence that MRSA has evolved an alternative division mechanism that allows it to replicate even in the presence of antibiotics.
According to Simon Foster, PhD, an author of the study and chair in microbiology at the University of Sheffield’s School of Biosciences, “These findings have important ramifications for the development of new antibiotics, but also for understanding the fundamental principles that underpin bacterial growth and division” and “will provide new ways to tackle this dangerous infectious organism.”
For this study, the researchers used atomic force microscopy to study how antibiotics change the architecture of cell wall peptidoglycan at the septal rings to prevent cells from replicating. They found that MRSA “adopts an alternative mode of cell division and shows an altered peptidoglycan architecture at the division septum” and that this change is enabled by “several possible chromosomal potentiator mutations,” according to the paper.
The next steps for the researchers include determining how MRSA is able to grow and divide in the presence of antibiotics using the new mechanism. They will also work toward identifying and developing inhibitors that can target the newly identified survival strategy.
“This is a fantastic example of how physics and biology can be brought together to understand the pressing societal challenge of antimicrobial resistance. We could not have made the discoveries without this synergy, fusing world-leading microscopy with genetics and microbiology,” said Jamie Hobbs, PhD, an author of the paper and a professor of physics at the University of Sheffield’s School of Mathematical and Physical Sciences. “Our research demonstrates the power of an interdisciplinary approach to address the basic mechanisms supporting the physics of life which are of such importance to healthcare.”
