Antibiotic-induced amino acid release - A new antimicrobial strategy?

Research Project, 2020 – 2024

Antibiotic-induced amino acid release is a recently discovered bacterial stress response that is mediated by mechanosensitive channels. The activation of mechanosensitive channels and subsequent release of osmolytes is a well-known reaction to hypoosmotic stress, but nothing is known about how and why it is triggered by antibiotics. Curiously, antibiotic-induced amino acid release is accompanied by accumulation of normally cytosolic amino acid synthases at the cell membrane.

In this proposal we want to investigate this newly discovered bacterial defense mechanism against antibiotics. We will investigate how antibiotics trigger the opening of mechanosensitive channels, how amino acid release confers antibiotic resistance, and why cytosolic proteins move to the membrane under stress. We will address these questions with a combination of cell biological and global -omics techniques.

Preliminary experiments have shown that impairing antibiotic-induced amino acid release strongly increase the activity of antibiotics. We will therefore examine the potential of this stress response as additional drug target. We will deliver the proof of concept that inhibiting mechanosensitive channels boosts antibiotic activity and develop an assay to identify suitable inhibitors.

To keep up with the alarming emergence of resistant superbugs, alternatives to antibiotics have to be taken into consideration. One alternative can be targeting stress responses like antibiotic-induced amino acid release.