One of the most alarmingly-plausible doomsday scenarios is the rise of “superbugs” – bacteria that are resistant to antibiotics, which could eventually make even the most basic infections lethal once again. Now, researchers at Imperial College London have found that a high-priority superbug resists drugs by closing its pores, and the discovery could lead to new ways to treat them.
The bacteria in question is known as Klebsiella pneumoniae, and as the name suggests it’s responsible for some types of pneumonia, particularly those caught by patients in hospital for other problems. Unfortunately these types of infections are increasingly resistant to antibiotics, including a class called Carbapenems, which are considered one of our last lines of defense.
So the researchers on the new study set out to investigate just how the bacteria are evolving resistance to these drugs. The team compared strains of K. pneumoniae that are resistant to Carbapenems to others that aren’t, looking for differences in their structures.
And sure enough, they found that the resistant bacteria had modified versions of a protein called OmpK36, and in some cases had lost it entirely. This protein is responsible for creating pores in the cell walls of the bacteria, which the drug molecules use to enter the cell to kill the bug. By reducing OmpK36, the bacterium has fewer and smaller pores and is therefore better at keeping the lethal antibiotics out.
Now that we understand this process better, scientists could try to come up with new techniques and drugs that could interfere with this mechanism. But that brings new challenges of its own.
“The modification the bacteria use to avoid antibiotics is difficult to get around,” says Gad Frankel, lead researcher on the study. “Any drugs to counteract this defense mechanism would likely also get blocked out by the closed doors. However, we hope that it will be possible to design drugs that can pick the lock of the door, and our data provides information to help scientists and pharmaceutical companies make these new agents a reality.”
Interestingly, this same mechanism that makes the bugs stronger could also introduce a new weakness. Blocking the pores may keep dangerous drugs out, but it also blocks out vital nutrients. The team ran tests in mice and found that the resistant bacteria grew slower than non-resistant strains. The trade-off is apparently worth it for the bacteria though.
This part of the discovery could hint at a possible treatment plan. Another recent study on fungus found success using existing drugs that reduce iron levels, starving the organism of nutrients. This kind of technique could potentially help fight K. pneumoniae too, since it’s already weakened by a lack of nutrients.
The new research was published in the journal Nature Communications.
Source: Imperial College London
