There are many forms of Escherichia coli. While lots are harmless members of the gut microbiome, others can cause serious infections. Some E. coli infections are challenging to eliminate because they are caused by antibiotic resistant forms, and some can also produce toxins. Now researchers have learned more about how toxin-generating E. coli can overcome antibiotics. This work has shown that some E. coli and other related bacteria known as Shigella carry a pump that can vigorously remove antibiotic drugs before they can take effect. This pump can be activated by human stomach acids. The findings have been reported in Nature Communications.
The super pump that E. coli uses is known as MdtF, and it helps E. coli live in the harsh environments in the human gastrointestinal tract. That harsh environment may even increase the efficiency of the pump, said first study author Ryan Lawrence, a molecular scientist at the University of Southampton.
"We've never fully understood how this MdtF protein helps protect E. coli bacteria when it's inside our bodies, until now,” said Lawrence. "Our research shows that this pump activates in response to the acid in our stomach, cleaning house and sweeping away toxins, even antibiotics. The MdtF pump supports biofilms which are very difficult to remove and may contribute to severe, reoccurring infections."
In this study, the investigators learned more about the structure of MdtF with cryo-electron microscopy. They determined that the pump can change shape to remove molecules that might disrupt the E. coli cell, a process that gets rid of stuff like toxins or antibiotics.
In the gut, oxygen levels are low and it can be very acidic. The MdtF pump loves these environments, where the pump is also upregulated. "This makes it more resistant to the drugs we use against E. coli,” noted co-corresponding study author Dr. Eamonn Reading, an associate professor at Southampton.
These findings might help researchers develop better treatments for some antibiotic resistant pathogens.
"Now we know the blueprint for this E. coli super-pump, we can work on a better way to jam this class of antibiotic cleaners,” Reading added. “We could create drugs that can break the pump, making the bugs increasingly defenseless against normal antibiotics."
