York researchers reveal how bacteria disguise themselves to avoid detection

Posted on 12 January 2023

Researchers in our Department of Biology and the Hull York Medical School (HYMS), along with collaborators at the Universities of Southampton and Oxford, have shed new light on a mechanism that disease-causing bacteria use to change the appearance of their cell surface.

Image credit: Kahlan Newman (CC BY 4.0)

Team

The team based in the York Biomedical Research Institute, had previously studied a protein that is able to move small chemical groups, called acyl groups, across the cell membrane which are then used to modify the bacterial cell surface. This is an important mechanism that food poisoning bacteria like Salmonella typhimurium use to change their appearance to predators and our immune system, and thus avoid detection and eradication.

In this new study, published in the journal eLife the York team led by Dr. Sarah Tindall, worked with Kahlan Newman, a PhD student at the University of Southampton and her supervisor Professor Syma Khalid, at the University of Oxford, to use computational methods to predict how this protein, called OafB, can function.

The work reveals that this protein contains a novel structure for a membrane-bound enzyme and importantly suggests how the acyl group can selectively work its way, or ‘wiggle’, through the membrane.

Domain

The authors started with a new computational structure prediction of the membrane domain, then tested whether this was likely correct and how it could work by combining computational approaches like molecular dynamics modelling with insights gained from their prior molecular analyses.

This showed the proposed structure is stable, and identified a pore and a molecular plug in the membrane, which is key to allow the acyl group ‘wiggle’. They integrated their elucidated structure of the second domain with this structural model to further explore how it works, which led to a detailed proposal of interactions between the two domains of OafB and its substrates. This study gives the first insight into how this family of proteins may work.

Family

Since OafB is part of a large family of proteins that moves acyl groups in many pathogens and other bacteria that enhances processes that help these bacteria be successful, the findings are of general importance.

Corresponding author Professor Gavin Thomas, of the Department of Biology, said: “It was really exciting to see how the power of computational structure prediction combined with molecular dynamics simulations shed light on a poorly understood protein.”
Senior author Professor Marjan van der Woude, of HYMS, said: “From what we now know about OafB we can seriously think about how to design inhibitors that could reduce the potential of some pathogens to colonise our bodies.”

The study was funded by the Biology and Biotechnology Research Council and the Engineering and Physical Sciences Research Council.

Notes to editors:

See the paper on eLifesciences.org