Bacteria can talk to each other via molecules they themselves
produce. The phenomenon is called quorum sensing, and is important when an
infection propagates. Now, researchers at Linköping University in Sweden are
showing how bacteria control processes in human cells the same way.
The results are being published inPLoS Pathogens with
Elena Vikström, researcher in medical microbiology, as the main author.
Bacteria 'talk'
When the announcement goes out, more and more bacteria gather at
the site of the attack -- a wound, for example. When there are enough of them,
they start acting like multicellular organisms. They can form biofilms, dense
structures with powers of resistance against both antibiotics and the body's
immune defense system. At the same time, they become more aggressive and
increase their mobility. All these changes are triggered when the communication
molecules -- short fatty acids with the designation AHL -- fasten to receptors
inside the bacterial cells; as a consequence various genes are turned on and
off.
AHL can wander freely through the cell membrane, not just in
bacterial cells but also our own cells, which can be influenced to change their
functions. In low concentrations white blood cells, for example, can be more
flexible and effective, but in high concentrations the opposite occurs, which
weakens our immune defenses and opens the door for progressive infections and
inflammations.
A team at Linköping University is the first research group to show
how AHL can influence their host cells. Using biochemical methods, the
researchers have identified a protein designated IQGAP, which they single out
as the recipient of the bacteria's message, and something of a double agent.
"The protein can both listen in on the bacteria's
communication and change the functions in its host cells," Vikström says.
Their laboratory studies were carried out on human epithelial
cells from the intestines, which were mixed with AHL of the same type produced
by Pseudomonas aeruginosa, a tough bacterium that causes illnesses
in places like the lungs, intestines, and eyes. With the help of mass
spectrometry, they have been able to see which proteins bind AHL.
"We have proof that physical contact between bacteria and
epithelial cells is not always required; the influence can happen at a
distance," Vikström says.
The team's discovery can open the door to new strategies for
treatment where antibiotics cannot help. One possibility is designing molecules
that bind to the receptor and block the signal path for the bacteria --
something like putting a stick in a lock so the key won't go in. It's a
strategy that could work with cystic fibrosis, for example, an illness where
sticky mucus made of bacterial biofilm and large amounts of white blood cells
is formed in the airways.
Journal Reference:
1. Thommie Karlsson, Maria V. Turkina, Olena
Yakymenko, Karl-Eric Magnusson, Elena Vikström. The Pseudomonas
aeruginosa N-Acylhomoserine Lactone Quorum Sensing Molecules Target IQGAP1 and
Modulate Epithelial Cell Migration. PLoS Pathogens, 2012; 8
(10): e1002953 DOI: 10.1371/journal.ppat.1002953
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