Quorum sensing is a bacterial communication process that relies on the production, detection, and group-
wide response to extracellular signaling molecules called autoinducers. Quorum sensing enables groups of
bacteria to synchronously alter behavior in response to changes in population density and species
composition of the vicinal community.
In Aim 1, an investigation of phage-bacteria-eukaryote quorum-sensing-mediated interactions will
be undertaken. The proposed research seeks to explore newly-discovered inter-kingdom quorum-
sensing-mediated communication pathways that shape host-microbe-phage interactions. Mutagenesis,
bioassays, small molecule purification, and crystallography will be used to define the mechanisms by
which phages, in response to host quorum-sensing information, launch their lytic programs. The native
cue that is released from lysed bacterial cells that appears to be the key input that activates the
phage quorum-sensing "eavesdropping" program will be purified. More complex mechanisms that underlie
phage infections of the human microbiome, how affected bacteria avoid phage infection, how phage infection
of microbiome bacteria affects health-promoting and harmful gut microbes will be investigated. The team
will use what is learned to guide the development of phage therapies to combat human diseases.
In Aim 2, the team will image the bacterial biofilm dispersal process and discover the key components.
Quorum sensing controls the development of surface-associated communities called biofilms, a predominant
form of bacterial life on Earth. Biofilms are notorious for causing infections and damage to surfaces.
Unlike biofilm formation, almost nothing is known about the second half of the biofilm lifestyle, biofilm
dispersal. The team will develop a new imaging system with light sheet fluorescence microscopy (LSFM)
that will enable imaging of the biofilm dispersal process. By imaging, at single-cell resolution, bacteria
exiting biofilms the team will discover when dispersal occurs, if cells leave individually or collectively, and
whether or not the process is globally synchronized. Using fluorescent reporters to quorum-sensing-
controlled genes, quorum-sensing activity during dispersal will be monitored. The unique and combined
contributions of the different autoinducers in driving/suppressing biofilm dispersal will be studied. This
aim will provide leads for manipulating dispersal, a key step in bacterial lifecycles incl uding those of global
RELEVANCE (See instructions):
Bacterial pathogens require quorum sensing for infection. An important practical aspect of these
investigations is the development of anti-quorum-sensing therapies including new phage therapies as
alternatives to traditional antibiotics.