Stomach ulcer drugs boost TB treatment effect

The bacterial infection tuberculosis - TB - is one of the world's deadliest diseases: around 10 million people per year fall ill with it, and in 2021 it killed one and a half million. The infection is notoriously hard to treat because not only is it mutating to become resistant to our antibiotics, but also because patients need to take medication of many months to effect a cure. As well as beign costly, this can lead to poor adherence and relapses. But not researchers at the University of Cambridge may have found a way to dramatically shorten treatment times: by simultaneously administering a common class of drug used to treat excess stomach acid and ulcers, as Lalli Ramakrishnan explains...

Lalli - The thing that we've discovered is that the TB bacteria have these pumps. They literally can pump out drugs that are administered to them, and they turn on these pumps when they're inside of us. And what we found is that many drugs have incidental activity against these pumps. And then when we screened these, uh, so-called proton pump inhibitors,

Chris - These are the ulcer drugs.

Lalli - The ulcer drugs had very good activity against the bacterial pumps. And so we went ahead and tested them in a lab-based experiment to see if they could reduce the time to treatment just in a. It's a strictly lab-based experiment, but it gives us a clue that we should go forward with these and move on to, say, animal models and people.

Chris - So in summary, then the microbe is cunning and it produces this pump, which it can turn on, which when you throw drugs at it, it can immediately chuck them. It's a bit like me seeing a hand grenade come through the window. So I quickly pick it up and lob it out again before it goes off <laugh> and saving my life in the process. And you have found a way of basically locking the window so it can't throw the hand grenade back out, and therefore the drug does detonate inside the cell. And it just so happens that proton pump inhibitors, things like omeprazole that we give for the stomach, happen to have as one of its side effects, this effect on these bacteria.

Lalli - Correct. It basically can clog up that pump, literally just clog it.

Chris - Will this work for other infections? Because there are other hard to treat infections where there's probably a similar sort of thing going on where it's hard to get the drug into the bug for long enough and it makes it hard to treat, it makes it expensive to treat. Could we try your trick elsewhere beyond just tb?

Lalli - Yeah. In fact, all bacteria have these pumps and the bacteria that we are particularly interested in is a bacterium that's quite related to TB. It's called Mycobacterium abscessus, which causes really bad disease in many parts of the world, including here. For example, you know, there've been a series of infections and even deaths and we would very much like to try that as our next goal to see if these pump inhibitors work, because those are even more recall to infection by far than TB.

Chris - But obviously you are doing this in a test tube at the moment. There must come a point where you're going to say, well, we now need to do the clinical trial. And presumably you could do that by, can you not look at the patient records and see some people who've been on treatment and had these drugs incidentally and find people who've got better quicker?

Lalli - The problem with looking at these records is that in a place where there's a lot of TB records are not necessarily the best and there are lots of, you know, extraneous factors. So it's very difficult. One needs to do a prospective trial, which we very much hope will happen.