How bacteria physically resist antibiotics

Stiffer cell walls and a diminished charge enable resistant bacteria to sidestep common antibiotics, a new study has found...

“Many of the drugs that we use to treat diseases with have stopped working because the bacteria have become resistant. Already now, about 700,000 people die from preventable diseases every year [because of antibiotic resistance],” says Maikel Rheinstadter from McMaster University in Canada.

According to Rheinstadter, most research undertaken in bacterial resistance focuses on the specific and unique aspects of each single species of bacteria. The new research though, published in Nature Communications Biology, takes a different approach: to look at whether there are “common properties amongst all these resistant bacteria to tackle [the resistance] issue more efficiently.”

The McMaster team used highly specialised equipment from the realms of physics and astronomy to peer at bacteria and drugs interacting at a molecular level. Seeing details at the scale of one millionth of the width of a human hair, they ran a series of experiments to look at how certain antibiotics work close-up, and compared the behaviour of both resistant and drug-susceptible bacteria.

The cell membranes of resistant bacteria, they found, carried a diminished charge compared with the membranes of otherwise identical drug-susceptible bacteria. This works similarly to a magnet: a lesser charge means that some antibiotics are less likely to be attracted to the resistant bacteria and are less likely to latch onto them. Second, the cell walls of the resistant bacteria are much stiffer than the cell walls of susceptible bacteria, which makes it harder for the drugs to puncture the wall and kill the cell.

Now that they have identified these two basic mechanisms of bacterial resistance - namely charge and stiffness - the McMaster team intend to expand their search by using their new technique to screen more bacteria and more antibiotics. This should allow them to test whether the discovery is, indeed, common to most or all cases.

Understanding the physical properties of antibiotic resistance, Rheinstadter believes, can be used as a tool to develop better antibiotics in the near term, and get on top of the bacterial resistance crisis we are facing going forward. He emphasises that this new discovery means that scientists now have two new handles with which to tackle the very problematic issue of antibiotic resistance...