Understanding how the ABC-F proteins mediate antibiotic resistance

Our ability to effectively prevent and treat bacterial infection with antibiotics represents one of the key foundations upon which modern medicine is built. Unfortunately, this foundation is rapidly becoming undermined by the widespread emergence of antibiotic resistance (AR), and the World Health Organization has declared AR one of the three greatest threats facing human health. The O’Neill laboratory at Leeds is actively pursuing several complementary approaches to better understand and address this phenomenon.
Proteins of the so-called ABC-F family are an important source of AR in ‘superbugs’ such as Staphylococcus aureus. Indeed, this protein family collectively provides resistance to a broader range of clinically useful antibiotic classes than any other. Until recently, the way in which these ABC-F proteins work to cause AR remained unknown. However, the O’Neill lab has now shown that they act to physically protect the bacterial ribosome from antibiotics, although the molecular mechanism by which this occurs remains to be established.
This studentship will employ biophysical techniques (principally X-ray crystallography and cryo-electron microscopy) to determine the 3D structures of members of AR ABC-F family, alone and bound to the ribosome, thereby yielding the first detailed insights into the mechanism of this family of AR proteins.


Please see the O’Neill lab website for more information about what we do and how we do it, and links to our published work:
http://www.fbs.leeds.ac.uk/staff/profile.php?tag=ONeill_AJ.