The study is the first to show that bacteria can change form in the human body, hiding the cell wall inside themselves. Concealing the cell wall means antibiotics have no target, providing a potential cause of resistance, according to researchers from Newcastle University.
Scientists used state-of-the art techniques to analyse samples from elderly patients with recurring urinary tract infections (UTI).
The research, known as “L-form switching”, shows that when antibiotics are present – such as in a patient with a UTI receiving penicillin or other cell wall-targeting antibiotics – the bacteria has the ability to change form.
Lead author, Dr Katarzyna Mickiewicz, 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 the 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.”
The research, published in Nature Communications, used samples obtained through a collaboration with clinicians at the Newcastle Freeman Hospital, part of Newcastle upon Tyne Hospitals Foundation Trust.
The World Health Organisation has identified antibiotic resistance as one of the biggest threats to global health, food security and development today.
In a previous study, the Errington lab team demonstrated that the immune system can also, to some extent, induce L-form switching but that antibiotic treatment has a much more profound effect.
According to the current research, 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.
Researchers also captured on video L-form bacteria isolated from a patient with UTI reforming a cell wall after the antibiotic had gone. This took five hours.
The team showed by a direct microscopy in transparent zebrafish model, that the L-form switching is possible in the context of whole living organisms, 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 reform 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.”
Additional reporting by agencies
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