Cause of antibiotic resistance identified

Cause of antibiotic resistance identified
E.coli L-form switching - so from walled to without a wall. Credit: Newcastle University, UK

Scientists have confirmed for the first time that bacteria can change form to avoid being detected by antibiotics in the human body.

Studying samples from with recurring urinary tract infections, the Newcastle University team used state-of-the art techniques to identify that a bacteria can lose its —the common target of many groups of antibiotics.

The research by the Errington lab which turns on its head current thinking about the bacteria's ability to survive without a cell wall, known as "L-form switching", is published today in Nature Communications.

The World Health Organisation has identified as one of the biggest threats to global health, food security, and development today.

Lead author, Dr. Katarzyna Mickiewicz researcher at Newcastle University said: "Imagine that the wall is like the bacteria wearing a high-vis jacket. This gives them a regular shape (for example a rod or a sphere), making them strong and protecting them but also makes them highly visible—particularly to human immune system and antibiotics like penicillin.

"What we have seen is that in the presence of antibiotics, the bacteria are able to change from a highly regular walled form to a completely random, cell wall-deficient L-form state- in effect, shedding the yellow jacket and hiding it inside themselves.

"In this form the body can't easily recognise the bacteria so doesn't attack them—and neither do antibiotics."

L-form—flimsy but survives

The research which used samples obtained through a collaboration with clinicians at the Newcastle Freeman Hospital part of Newcastle upon Tyne Hospitals Foundation Trust organised by Dr. Phillip Aldridge and Dr. Judith Hall shows that when antibiotics are present—such as in a patient with a UTI receiving penicillin or other cell wall-targeting antibiotic—then the bacteria has the ability to change form, losing the cell wall which is often the target of the antibiotic.

This video captures the transition on osmoprotective media from L-form to walled form after the antibiotic was removed. Credit: Newcastle University, UK

In a previous publication, which appeared in Cell in 2018 (10.1016/j.cell.2018.01.021), the Errington team demonstrated that our immune system can also to some extend induce L-form switching but treatment with have a much more profound effect. Current study showed that L-forms of various bacterial species typically associated with UTIs including E. coli, Enterococcus, Enterobacter and Staphylococcus were detectable in 29 out of 30 patients involved in the study.

In this L-form the bacteria are flimsy and weaker but some survive, hiding inside the body.

The research also captured on video for the first time, L-form bacteria isolated from a patient with UTI re-forming a cell wall after the antibiotic had gone—taking just 5 hours. The team was also able to show by a direct microscopy in transparent zebrafish model, that the L-form switching is possible in the context of whole living organism and not only in artificial conditions in the lab.

Dr. Mickiewicz explained: "In a healthy patient this would probably mean that the L-form bacteria left would be destroyed by their hosts' immune system. But in a weakened or elderly patient, like in our samples, the L-form bacteria can survive. They can then re-form their cell wall and the patient is yet again faced with another infection. And this may well be one of the main reasons why we see people with recurring UTIs.

"For doctors this may mean considering a combination treatment—so an antibiotic that attacks the cell wall then a different type for any hidden L-form bacteria, so one that targets the RNA or DNA inside or even the surrounding membrane."

Diagnosis

The research also found that L-form bacteria is difficult to identify by traditional methods used in hospital as the gel used in effect "pops" the bacteria as they are put into it.

A special osmoprotective detection method was needed to support the weaker L-form , enabling them to be identified in the lab.

The team will be furthering the research with trials in patients who have had treatment.


Explore further

Bacteria under stress can live without cell wall

More information: Possible role of L-form switching in recurrent urinary tract infection. Katarznya Mickiewicz et al. Nature Communications (2019). DOI: 10.1038/s41467-019-12359-3 , https://nature.com/articles/s41467-019-12359-3
Journal information: Nature Communications , Cell

Citation: Cause of antibiotic resistance identified (2019, September 26) retrieved 15 October 2019 from https://phys.org/news/2019-09-antibiotic-resistance.html
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User comments

Sep 26, 2019
So how do bacteria "know" when they need to change or remove their cell wall and when it's safe to revert? Obviously it's the presence of the antibiotic but how is a single-celled organism responding like this? And can we then attack whatever mechanism they use to achieve this survival technique, making the antibiotics effective again?

Sep 27, 2019
For doctors this may mean considering a combination treatment—so an antibiotic that attacks the cell wall then a different type for any hidden L-form bacteria, so one that targets the RNA or DNA inside or even the surrounding membrane

Bacteria have evolved a rather clever means to evade antibiotics, quite possibly due to our misuse/overuse. And, the solution is to use a cocktail of even more antibiotics so that they can learn to evade them also. The pharmaceutical's leadership must be dancing in their boardrooms.
How about applying a well planned pulse treatment of the already effective antibiotic to match the periods when they are in their skins.

Sep 30, 2019
So how do bacteria "know" when they need to change or remove their cell wall and when it's safe to revert? Obviously it's the presence of the antibiotic but how is a single-celled organism responding like this? And can we then attack whatever mechanism they use to achieve this survival technique, making the antibiotics effective again?


As your quotes indicate, there's no knowing involved, possibly not even any complex sensing, just a simple direct reaction to the antibiotic. As the article indicates, there may be no need for a treatment to counter this, because it leaves the bacteria in a highly vulnerable state, so a follow-up treatment that takes advantage of that could be highly effective. Also, if the patient's immune system can be strengthened, it could finish off the infection naturally.

At one time, antibiotic resistance was regarded as a good case study of evolution in action -- are there still examples of antibiotic resistance that provide such models?

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