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Mutated IdsD proteins for treatment of Proteus mirabilis infections

Proteus mirabilis is part of the normal flora of the human gastrointestinal tract. It can also be found free living in water and soil. When this organism, however, enters the urinary tract, wounds, or the lungs it can become pathogenic. It commonly causes urinary tract infections and the formation of stones. Being a social bacterium that can recognize self versus non-self, the swarming colonies expand outward on surfaces at centimeter-scale distances via the collective motility of individual cells. Colonies of genetically identical populations can merge, whereas distinct strains remain separate and form a visible boundary. A functional Type VI Secretion System (T6SS) and Ids proteins essential for boundary formation. IdSD and IdSE proteins each contain a variable region, and together encode the strain-specific identity information necessary for this self-recognition. Team of Prof. Gibbs identified the logic behind the Ids-based cell-cell communication, by providing evidence that the self-identity protein IdsD is communicated from one cell to another and that interactions with IdsE in the recipient cell determine the recognition behavior. Lack of this T6SS-dependent interaction negatively impacts swarm colony expansion, but not viability, suggesting IdsD may represent a class of non-lethal T6SS effector proteins.

Applications

Proteus mirabilis commonly cause urinary tract infections under long-term catherization, as well as sepsis and systemic inflammatory response syndrome (SIRS) due to contac between wounds and infected surfaces. It can also colonize the lungs and cause pnemonia due to hospital breathing equipment and causes pneumonia. The cell-cell communication mechanism revealed by Prof. Gibbs significantly impacts the swarm colony expansion that cause infections to spread on contact surfaces like catheters. These molecular insights provide a roadmap to develop new agents such as mutant IdsD proteins to treat catheter-associated urinary tract infections.

Intellectual Property Status: pending

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