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