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native carbon electrode surface is sufficient for electrochemical analysis, and
these substances have been readily detected in or near the surface of single
cells. In fact, these electrodes, at present, are the only available technique to
measure the exocytotic release of neurotransmitters from single cells [1]. An
overview of the application of electrochemistry with ultra-microelectrodes in
neuronal microenvironments has been compiled by Clark et al. [19]. In chapter
8 we present progress toward the realization of molecular-scale electrochem-
ical probes suitable for integration into whole-cell microscale and nanoscale
systems.
Cell-to-Cell Communication
In addition to the coupling of information between cells using the action po-
tentials described above, communication of signals between whole-cell com-
ponents can be accomplished through the naturally occurring chemical signals
used by microbial cells to coordinate population-level processes. Communica-
tion via small molecular intermediates has been demonstrated to regulate several
diverse processes in bacteria including development, conjugation, pathogene-
sis, antibiotic production, symbiosis, competence, and bioluminescence. Ev-
idence for cell-to-cell communication in bacteria was first obtained for the
process of quorum sensing (QS). QS is a cell-cell communication network that
enables bacterial populations to collectively regulate their behavior based on
cell density, serving as a way for bacteria to coordinate their metabolic efforts
for specific functions such as infection onset, antibiotic production, or biofilm
formation [30, 47, 121]. This intercellular exchange relies on self-generated,
low-molecular-weight, diffusible signal molecules called autoinducers (AIs).
AI molecules released by a single, free-living bacterium do not accumulate to
high enough concentrations to be detected. However, when a sufficient bacte-
rial population density is reached, AI concentrations achieve a threshold level
that allows individual bacteria to coordinately activate or repress specific gene
expression.
QS was first identified in the marine bacterium Vibrio fischeri , where it con-
trols expression of bioluminescence [99]. The V. fischeri QS network consists of
AI molecules called N -acylhomoserine lactones (AHLs). AHLs are synthesized
from precursors by a synthase protein, LuxI and, upon reaching a critical thresh-
old, interact with a transcriptional activating LuxR protein to induce expression
of genes responsible for bioluminescence. Bacteria use QS to control a variety
of cell-density-dependent functions, including virulence [119], iron regulation
[15], 100], and biofilm formation [27, 29]. One of the best-characterized QS
model systems available is that of Pseudomonas aeruginosa , an opportunistic
pathogen [89] that can serve as a model organism for pathogenic processes. The
P. aeruginosa QS system derives from two pathways, designated las and rhl ,
which function in a hierarchical nature to regulate more than 40 genes involved
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