Flux-sensing by transporter/kinase pairs – need-based activation of antibiotic resistance.
18 July 2019 - 18 July 2019
11:00am - 12:00pm
Speaker: Dr Susanne Gebhard
Hosted by: Prof. Mark Pallen
Abstract: Resistance against antimicrobial peptides in many Gram-positive bacteria is mediated by detoxification systems that are comprised of a two-component regulatory system and an ATP-binding-cassette (ABC) transporter. The histidine kinases of these systems depend entirely on the transporter for detection of antimicrobial peptides, suggesting a novel mode of signal transduction where the transporter constitutes the actual sensor. We have taken a multi-disciplinary approach combining experimental and computational methodology to unravel the mechanistic details of this unique signaling pathway, exemplified by the bacitracin resistance system BceRS-BceAB of Bacillus subtilis. We show that the transporters and kinases form a sensory complex in the membrane, and that the histidine kinase directly responds to changes in the activity of the transporter. This appears to occur via complete control of kinase conformation by the transporter, which to our knowledge is unprecedented among bacterial signaling systems. We propose that this novel regulatory strategy effectively implements a flux-sensing mechanism, allowing the cell to adjust the rate of de novo transporter synthesis to precisely the level needed for protection.
Biography: Susanne trained in molecular microbiology in Germany and New Zealand. Her PhD work was focused on transport systems and their regulation, while her first postdoctoral project saw her shift her research towards regulation of antibiotic resistance. With her move back to Germany in 2009, Susanne combined these two interests and began to investigate how a transport system can play an active role in bacterial signaling. With this new project, she established an independent junior research group in Munich. In 2014, she moved to the UK to take up a lectureship in Medical Microbiology at the University of Bath, where she is continuing and expanding this work.