Description:
Quorum
Sensing is an essential form of intercellular communication used by many types
of common bacteria, and many pathogenic bacteria use quorum sensing to attack
and invade the human host. Quorum Sensing is used by bacteria to detect a
critical cell number, which is the cell population required for pathogenic
bacteria to release effective amounts of toxins that overcome host immune
defenses. In a sparse pathogenic bacteria population, the early release of
toxins would stimulate the human immune system to neutralize the bacteria.
Pathogenic bacteria have developed an evolutionary strategy whereby they can
sense when they have amassed a critical cell number before producing virulence
factors which enable the bacteria to persist in the human host and to cause the
infection.
Researchers
at Princeton University have discovered the bacterial gene and molecule
necessary for Quorum Sensing. The AI-2 molecule is a signaling molecule
produced by some species of bacteria. Each bacterium continually produces
AI-2 molecules that flow freely across its cell membrane. In a low cell
population, AI-2 molecules are swept away by diffusion. In a high cell
population, AI-2 molecules begin to flow from one bacterial cell into another
where they bind to receptor proteins triggering a biochemical reaction. In
the case of pathogenic bacteria in a high cell population, AI-2 molecules bind
to LuxP receptor proteins triggering pathogenesis. The LuxS gene is the
bacterial gene responsible for producing AI-2 molecules. Hundreds of
species of bacteria contain the LuxS gene, including pathogenic bacteria such as
Escherichia coli, Salmonella typhimurium, Vibrio cholerae, Staphylococcus
aureus, Bacillus anthracis, and Enterococcus faecalis.
The structures of the AI-2 molecule and the LuxP receptor protein have been
elucidated by researchers at Princeton University. Inhibitor development
obstructing the Quorum Sensing pathway is now possible. It is proposed
that analogues of AI-2 be developed to bind to the LuxP receptor protein, in
effect, blocking the binding of AI-2 and preventing its subsequent triggering of
pathogenesis. This therapeutic compound would be a new type of antibiotic
that would disrupt pathogenic bacteria communication and, therefore, prevent
pathogenesis. It is anticipated that this new class of antibiotics would
not be subject to the classic mechanism of increasing bacterial resistance to
common antibiotics, which is a current problem in medical treatment of bacterial
infections.
Patents
Issued:
US
# 6,559,176 Compounds and methods for regulating bacterial growth and
pathogenesis
US
# 6,720,415 Compositions and methods for regulating bacterial
pathogenesis
US
# 6,780,890 Compounds
and Methods for Regulating Bacterial Growth and Pathogenesis
US
# 6,844,423 Compositions and
Methods Regulating Bacterial Growth and Pathogenesis
US
# 6,864,067 Compositions
and Methods for Regulating Bacterial Pathogenesis
US
# 6,936,435 Compositions and Methods Regulating Bacterial
Growth and Pathogenesis
US
# 6,942,986 Compositions and
Methods Regulating Bacterial Growth and Pathogenesis
US
# 7,208,612 Crystals
of LuxP and Complexes Thereof
US
# 7,326,542 Compositions
and Methods for Regulating Bacterial Pathogenesis
US
# 7,666,619 Compositions
and Methods for Regulating Bacterial Growth and
Pathogenesis