Researchers in the group of Jan Michiels (VIB-KU Leuven
Center for Microbiology) identified a mechanism of how
sleepy bacteria wake up. This finding is important, as
sleepy cells are often responsible for the stubbornness of
chronic infections. Findings published in Molecular Cell
reveal new perspectives on how to treat chronic infections,
for example by forcing bacteria to wake up.
Sleeping bacteria
Bacteria are able to fall into a deep sleep. These sleeping
bacteria are called ‘persisters’ and they can be
found in every type of bacterial population studied so far,
including important human pathogens. From a patient’s
point of view, persisters are unwanted as their sleeping state
makes them insensitive to antibiotics.
These sleeping bacteria may wake up spontaneously and colonize
the host leading to a return of the infection. Hence, persisters
are associated with the failure of antibiotic therapy when they
are not killed by the immune system. Until now, it was unknown
how these cells were able to revert from dormant to active
state. These new results provide insight into how persisters
wake up.
Breaking links to wake up
To investigate how persisters wake up, the scientists used an E.
coli model system based on HokB. HokB is a peptide – a
small cousin of proteins – which is known to promote the
development of persister cells by forming pores in the bacterial
cell membrane. This results into a rapid loss of energy, pushing
the bacteria into a low energy state or deep sleep. Importantly,
this pore formation is only possible when two HokB peptides are
linked together. The awakening of these sleeping bacteria is
possible only when the link between the peptides is broken. This
in turn breaks up the pore. Only when the pore is degraded,
cells are able to energize again by consuming available
nutrients.
Lead author Dorien Wilmaerts (VIB-KU Leuven Center for
Microbiology) says: “You can compare this process with a
punctured tire: you take out the spike first, and then inflate
it again. Doing it the other way around does not make
sense.”
Getting rid of chronic infections
Persister cells are responsible for chronic infections that keep
returning. Examples are urinary tract infections by Escherichia
coli, lung infections in cystic fibrosis patients by Pseudomonas
aeruginosa, or tuberculosis by Mycobacterium tuberculosis. How
persister cells wake up is a long-standing question in
persistence research. This work is the first to provide a
detailed mechanistic understanding of an awakening mechanism and
opens up new perspectives on how to stimulate awakening of
deeply dormant cells.
Prof. Jan Michiels (VIB-KU Leuven) says: “Results from
this work may help us to discover novel molecules and to design
new strategies to eradicate persisters. Combinations of
molecules stimulating awakening together with classical
antibiotics could eradicate chronic infections.”
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Publication
Funding
This work was supported by grants from the FWO (G055517N,
G047112N, G0B2515N) and the Interuniversity Attraction
Poles-Belgian Science Policy Office IAP-BELSPO (IAP P7/28).
Source:
VIB (the Flanders Institute for Biotechnology)
