Professor Helen J. Wing (Life Sciences) and a team of researchers published their findings in a top-ranked microbiology journal, mBIO, and received the honor of "editors pick" in the journal. The paper lists Taylor Gerson, a Ph.D. candidate in the Wing lab, as its first author along with four other members of the Wing Lab. The published work also includes collaborations with professor Ronald Gary (Chemistry and Biochemistry), as well as researchers from the National Library of Medicine in Bethesda, Maryland.
The Wing Lab studies the molecular details of how a group of bacteria called Shigella cause dysentery in humans. The work is important because these bacteria are responsible for the second leading cause of diarrheal deaths world-wide.
The researchers discovered that VirB (one of the master regulator proteins needed for the bacterium’s virulence), is itself regulated by a small signaling molecule called cytidine-triphosphate (CTP) that also serves as a building block for RNA. The work used the techniques of isothermal titration calorimetry and differential radial capillary action of ligand assay to demonstrate that CTP (but not other related nucleotides) binds directly to the VirB protein with specificity. In addition, the researchers showed that when the amino acids responsible for that binding are altered, Shigella bacteria containing the mutant VirB protein are no longer pathogenic.
Understanding how CTP controls the function of VirB could lead to a much better understanding of how small molecules control the batteries of genes needed to cause disease. It also raises the possibility that new strategies could be developed to kill or cripple bacteria using therapeutics that are not part of the current antibiotic arsenal for which resistance is fast becoming a critical health concern.