A suite of highly specific, proprietary bacterial drug targets in staphylococcus aureus, that can be used individually or as a group to develop small molecule or peptide drug leads with powerful anti-infectives properties.

Inhibition of bacterial iron uptake mechanisms as an effective means to abrogate bacterial infection

Keywords: Anti-Infectives, Gram-Positive Pathogens, Antibiotic Resistance, Hospital Related Infections; Bacterial Iron uptake

DESCRIPTION OF THE INVENTION: The present technology suite is based on the identification of a suite of highly specific, proprietary bacterial drug targets in staphylococcus aureus, that can be used individually or as a group to develop small molecule or peptide drug leads with powerful anti-infectives properties. The underlying mechanism of action is to inhibit bacterial iron uptake mechanisms and thus to starve the pathogen of its critical food source. One target (UWO-AE-008) is an iron-regulated, nine gene operon (sbn) whose products are involved in the synthesis of a siderophore (secreted iron-chelating agent) in S. aureus. Expression of the sbn operon is crucial for iron-restricted growth of S. aureus both in vivo and in vitro. Other targets include the SirABC protein complex (UWO-AE-028) which is used to transport the S. aureus siderophore and the IsdABC proteins (UWO-AE-009) which are anchored to the cell wall of S. aureus and are used in the binding of heme.

BACKGROUND: Staphylococci are capable of causing a diverse array of diseases, ranging in severity from food poisoning and urinary tract infections to toxic shock syndrome, bacteremia and endocarditis. Arguably the most important cause of life-threatening bacterial infections in the world, Staphylococcus aureus is the leading cause of hospital-related diseases in the United States, the most prevalent pathogen isolated from skin and soft-tissue infections, one of the four leading causes of food-borne illness, and one of the most common agents of infective endocarditis. The recent identification of isolates of S. aureus resistant to the antibiotic vancomycin, considered the last line of defense against bacterial infection, further underscores the importance of identifying novel therapeutic targets against this important pathogen. Bacterial iron acquisition systems have received recent attention as a promising therapeutic target. This is due to the fact that the majority of bacterial pathogens require iron to infect. Iron is the only limiting nutrient to bacterial growth inside the human host and iron limitation is an important innate human defense against bacterial infection.

POTENTIAL ADVANTAGES/USES: This technology presents a unique tool to identify and develop novel classes of drugs and methodologies to prevent and treat S. aureus infections. It will be of interest to pharmaceutical and biotechnology companies developing diagnostic tools, vaccines and/or therapeutics in the area of hospital related infections, treatment resistant pathogens, sepsis, bacteremia and infectious endocarditis. 

DEVELOPMENTAL STAGE: Preclinical proof of principle

REF: UWO-AE-008, UWO-AE-028 and UWO-AE-009 

Preclinical

US and PCT applications filed.

This technology is available for licensing and/or collaborative approach