Background
The emergence of multidrug resistance bacteria has created the need for the development and commercialization of novel antibiotics that work differently than existing agents. Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella Pneumoniae, are responsible for approximately two-thirds of deaths caused by bacterial infections. Researchers have determined that the Gram-negative bacterial cell envelope serves the dual purpose of protective barrier for the cell and a gateway for the entry of essential elements and nutrients. The cell envelope consists of the concentric cytoplasmic and outer membranes, separated by an aqueous periplasmic space. The outer membrane protects the cell from hydrophobic antibiotics, degradative enzymes, and detergents while allowing small (< 600 Da) hydrophilic nutrients entry by passive diffusion through outer membrane porin proteins.

Invention Description
A unique target has been identified, which Gram-negative bacteria use to obtain essential nutrients and compete successfully in a host environment. By blocking specific protein interactions and thus a cascade of cellular events leading to an energization signal, the Penn State inventor has identified a novel target for novel antibiotic action. The invention’s strength is enhanced by the nature of the proposed antibiotic. The antibiotic does not target proteins in the outer membrane and can enter by multiple porin-based routes. Once past the outer membrane, it will directly target subsequent energy and signal transduction processes. If the bacteria become resistant to it, they will also have become unable to acquire the essential nutrients.

File Number: 3771 

Other Information:

Status of the Invention

The inventor intends to further develop the invention by identifying small molecule peptides (< 600 Da), capable of porin transport, that interrupt the critical protein interaction. Larger peptides (50-60 kDa) offer a possibility to be employed by exploiting the target’s transport mechanism directly.