The story behind our latest paper
A few years ago, Kuba started to find evidence that strong disturbances in cellular metabolism (which we found to lead to persister cells) would also lead to lowered intracellular pH. Once he finished his PhD work, Hannah has taken over the project and she found that with protonated ppGpp (i.e. due to the decreased intracellular pH) the ppGpp-hydrolase activity of SpoT is lowered. As increased ppGpp levels are associated with persistence, we thought we had the mechanisms of how a distorted metabolism would lead to persistence. Yet, there were two problems. First, with pH being such a global variable, it was hard to show causality. Second, a strain that was unable to synthesize any ppGpp did essentially was just as persistent. The lucky instance was that I met Jan Michiels from the KU Leuven at a conference, who presented results where they had found that mutations in the proton export function of the respiratory chain Complex I led to increased persistence. Jan at the time did not know the mechanistic connection between this mutation and persistence. Yet, ‘mentally’ putting our results together, we hypothesized that intracellular pH could be the connection. Thus, we decided to team up and the result (after another 3.5 more years and much more work) is the paper that was published today in Nature Communications!