Single‐molecule tracking and super‐resolution imaging shed light on cholera toxin transcription activation

SummaryBecause of their small size, bacterial cells have long kept details about their inner workings a secret. We are starting to decipher their mechanistic secrets, in no small part due to the development of single‐molecule and super‐resolution fluorescence imaging, the subject of the 2014 Nobel Prize in Chemistry. These new methods have yielded a surge of discoveries about the subcellular organization and dynamics inside microbes. One example is an increased understanding of the virulence pathway within the cholera‐causing microbe, Vibrio cholerae. Here, expression of the cholera toxin is regulated by an unusual step: transcription is activated by two inner‐membrane proteins. Relating potential cooperative mechanisms between these two membrane‐bound proteins and transcription activation is difficult using ensemble methods, which could obfuscate any underlying heterogeneity. Recent efforts using single‐molecule tracking and super‐resolution imaging have begun to unravel the heterogeneity. The results support a mechanism in which one membrane protein recruits the other in order to activate transcription. The study helps to explain the relationship between the two proteins in chole