A new discovery in ‘dormant’ bacteria, also called persisters, could be interesting to develop more efficient antibiotic treatments. This is shown by research by KU Leuven and the Flemish Institute for Biotechnology (VIB). The researchers found that the moment when the ‘sleeping’ bacteria wake up is linked to the development of resistance to antibiotics.
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Door Redactie Online
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Persistors are bacteria that do not feel an antibiotic treatment: they are inactive and can thus survive a treatment. When persisters awaken from their sleep in an environment free of antibiotics, they can multiply again and rekindle the infection.
Large variation
Until now, it was unclear what exactly triggered the awakening mechanism. It was also difficult for researchers to examine these ‘awakening’ cells, because such cells are scarce, and they are only temporarily in that situation.
It was already clear that the moment a sleeping cell wakes up, it loses its tolerance to antibiotics. Once a dormant cell becomes active again, the antibiotic treatment can kick in. However, a large variation in cells has been observed: one cell wakes up faster than the other.
DNA damage
Researchers from VIB-KU Leuven have now identified a few targets that reveal when such a sleeping cell wakes up. The weak spot of persisters has thus been identified. «During antibiotic treatment, persisters build up DNA damage. The cells will repair this DNA damage during awakening, as this is essential for persistence survival,” explains postdoctoral researcher Dorien Wilmaerts. “We have shown that DNA damage repair underlies the timing of awakening and contributes to the emergence of resistance.”
When these repair mechanisms are activated in persisters, they can thus prevent resistance. “Those mechanisms are therefore an interesting target for the discovery of new antibacterial drugs.”
acidification
Another important discovery was made together with the University of Groningen. The researchers found that extremely tolerant bacterial cells had significant acidification inside. The acidification turned out to eliminate the main target of the antibiotics: so the bacteria could continue to survive, despite being subjected to antibiotic treatment.
“Countering the acidification of bacteria could be a standardized way to improve existing antibiotic treatments,” said Professor Jan Michiels, who led the research team. “Now that we understand how to wake up the dormant bacteria, the long-awaited antipersistor therapies seem within reach.”
