Sleeping bacteria prevent antibiotics from working

25 July 2019

 Sleep is important. In humans, in fact, sleep is a matter of life and death. This is also true for bacteria.


Sleeping bacteria

Surprisingly enough, bacteria are champion sleepers. When they enter their slumber almost nothing can disturb them. They are even immune to antibiotics while they’re dozing off. The sleeping bacteria that survive an antibiotic treatment are known as ‘persisters’. These persisters will wake when the antibiotic barrage has passed. They return to their active live and can reproduce again.

Since there are only a few persisters in a bacterial population, our immune system can usually take care of them. That’s why you’ll be fully cured following antibiotic treatment in most cases. Sadly, that’s not always so. People suffering from mucoviscidosis, better known as cystic fibrosis, are an example of people who are not always helped by antibiotics. The immune system of these patients isn’t always able to clear their system of all persister-bacteria. That’s why these people often get ill again after an antibiotic treatment. The majority of these patients eventually dies at a young age as a consequence of a bacterial infection.

The roots of persistence

But what causes some bacteria to become persistent? My colleagues and myself at the VIB-KU Leuven Center for Microbiology and KU Leuven have looked into this. We showed that the E. coli bacterium can fall asleep by pumping out energy. To do this, we used HokB, a protein that makes pores into the ‘skin’ of the bacterium that allows this energy to flow away.

We went a step further and discovered that these pores are only formed in the strongest bacteria, which allows them to fall into a deep, but brief, sleep and become immune to the antibiotic we used. When they awoke from their short nap, they could grow again. So, HokB led to the failure of the antibiotic treatment by allowing strong bacteria to have a brief, reinvigorating nap. 

Whereas sleeping bacteria were immune to antibiotics, their awake colleagues were not. They perished.

Wake up!

How can this knowledge help us fight persisters? Well, we can prevent them from falling asleep. In our research, we found that components that blocked the pores – and thus prevented energy from streaming out – reduced the number of persisters. Another strategy is waking up the sleepers. For example, we’re working on ‘alarm clocks’ that wake sleeping bacteria so that they can be targeted by antibiotics. Finally, there is an ongoing quest to find antibiotics that can even be effective against the sleepers.

The recent published work from the lab of Jan Michiels is a step in the right direction in the fight against the failure of antibiotics, which has already troubled the sleep of many patients and physicians.

If you’re interested in the scientific publication on the role of HokB in bacterial persistence, you can check it out here.


By Dorien Wilmaerts & Liselot Dewachter

(Previously published in Dutch on Eos Blogs)​


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BIO

Dorien Wilmaerts is a microbiologist who is working as PhD student at the VIB-KU Leuven Center for Microbiology. She is trying to figure out how bacteria survive antibiotic treatments and grow afterwards. Her research will hopefully relegate the failure of antibiotics to the past.


 

Liselot Dewachter is also a microbiologist who works as postdoc at the VIB-KU Leuven Center for Microbiology. In her research, she hopes to discover how bacteria grow and procreate. A better understanding of this could lead us to figure out how to stop their growth and, in doing so, fight important pathogens.​