Efflux, the movement of molecules from inside a cell to outside, is a basic molecular function for all living things, and it’s particularly interesting for biologists concerned about antibiotic resistance — one way bacteria can resist antibiotics is by “spitting” antibiotic molecules out before they do damage. Targeting the molecular pumps involved in efflux may help overcome that resistance, and a new study by CSUN molecular biologists shows that disrupting efflux pumps could literally stop bacteria in their tracks. The study, published online ahead of print in the journal mSphere, shows that a molecule known to regulate an important efflux pump also plays a role in bacterial cells’ mobility.
MSci alumni Jessica Maldonado and Barbara Czarnecka worked with Biology Lecturer Dana Harmon and Associate Professor of Biology Cristian Ruiz-Rueda to trace the effects of a regulatory protein called AcrR. AcrR is known to suppress efflux in the bacterium E. coli, including efflux of antimicrobials. However, suppressing AcrR’s action also boosts the activity of dozens of genes involved in movement and the synthesis of the flagellum, the whiplike structure that propels an E. coli cell through its environment. The team used bioinformatic analysis of the E. coli genome to identify regions that could be bound by, and regulated by, AcrR. They confirmed that AcrR can bind to a promotor region called flhDC in an in vitro test, and used quantitative PCR to show that expression of flhDC is suppressed in the presence of AcrR. Finally, they measured the motility of E. coli cells treated with AcrR, and saw that they were, indeed, slowed down.
Based on their results, the coauthors propose a new model of E. coli‘s response to antimicrobials, in which AcrR plays a role in boosting efflux and mobility — so a bacterial cell’s removal of a toxin is coupled to escaping the toxin’s source. They suggest AcrR plays a key role in sensing and responding the accumulation of antimicrobials inside the cell, and thus directs the cell’s responses to that danger.
The full paper is available Open Access on the journal website.
Image: The molecular structure of AcrR. (Cristian Ruiz-Rueda)