A signaling receptor that aids bacterial communication may provide a
target for reducing virulence without antibiotics
For decades, microbiologists
thought that bacteria act individually, unaware of their multitudinous
counterparts involved in causing the same infection. In the past two decades,
however, they have discovered that many species of bacteria ‘communicate’. In
fact, bacteria can signal to each other that their numbers are sufficient to
launch a coordinated attack.
Owing to the relative newness of
this research area, few of these cell-to-cell signaling systems, known as
quorum sensing, have been described. Now, by working with Burkholderia
cenocepacia, an opportunistic pathogen that infects cystic fibrosis patients, a
research team led by Lian-Hui Zhang from the A*STAR Institute of Molecular and
Cell Biology (IMCB) has described a previously unknown quorum-sensing system
that is present in many human bacterial pathogens1.
Many types of individual
bacterial cells send and receive ‘messages’ via chemical signals called
quorum-sensing (QS) molecules. When concentrations of QS molecules reach a
threshold, individual bacterial cells simultaneously activate their virulence
genes. By identifying the signaling molecules and decoding these communications,
researchers may also be able to reduce bacterial virulence by interrupting
these conversations. Such treatments could provide an alternative to
antibiotics.
For the QS molecule of B.
cenocepacia, BDSF, Zhang and his co-workers identified a novel receptor, RpfR.
The researchers produced mutant bacteria that lacked either the receptor RpfR,
or the capacity to produce the signal BDSF. Both types of mutant bacteria
showed decreased motility, produced fewer host-degrading enzymes, and were less
able to form biofilms — bacterial aggregates encased in slime — indicating that
BDSF and RpfR act together to send and receive the virulence signal.
Zhang and his co-workers also
showed that, unlike other QS receptors, RpfR is a multitasking molecule. In
other systems, after the receptor binds the QS molecule, it recruits another
molecule to perform the next step in the signaling cascade and trigger gene
expression. In the quorum-sensing system of B. cenocepacia, however, RpfR binds
BDSF, then changes shape and performs the next step itself. Combining the two
functions in a single molecule expedites the signaling process, and enables
bacteria to adapt very quickly to changing environmental conditions.
The team’s search of known
bacterial genomes showed that the system is present in many other pathogenic
bacteria, including several groups that produce opportunistic infections in
immune-compromised patients. “We would like to design chemical compounds to
block the BDSF receptor, to compete with BDSF signals and reduce the virulence
and pathogenicity of B. cenocepacia,” says IMCB team member Yinyue Deng.
he A*STAR‐affiliated researchers contributing to this research
are from the Institute of
Molecular and Cell Biology
References
- Deng, Y., Schmid, N., Wang, C., Wang, J.,
Pessi, G. et al. Cis-2-dodecenoic acid receptor RpfR links
quorum-sensing signal perception with regulation of virulence through
cyclic dimeric guanosine monophosphate turnover. Proceedings of
the National Academy of Sciences USA 109, 15479–15484
(2012). | article
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