Emanuel Hanski , PhD, Carlos Hidalgo-Grass, PhD, and Allon E. Moses, MD, Department of Clinical Microbiology and Infectious Diseases, Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital.
Background
Many efforts are focused on developing novel antibacterial agents. A particular promising approach is to identify compounds that neither kill bacteria nor inhibit bacterial growth, but instead inactivate specific virulence mechanisms.
This might lead to a self-limiting infection without progression to stages of systemic diseases. In addition, inactivation of virulence mechanisms does not pose a direct strong selection pressure for development of drug resistant strains.
Group A streptococcus (GAS) is a common pathogen of the throat and skin. It causes infections of varying severity, ranging from uncomplicated superficial infections to severe life-threatening infections. The past decade has witnessed a worldwide increase in severe invasive GAS infections, including streptococcal toxic shock syndrome and necrotizing fasciitis (NF) the “flesh eating bacteria”. GAS has remained sensitive to penicillin, nevertheless early use antibiotics do not influence NF severity, and the case-fatality rate ranges from 30% to 70%.
This emphasizes the urgent need for developing new means to combat these aggressive, life-threatening infections.
Market
We collected over two years GAS isolates from 24 acute-care hospitals in Israel and obtained reports describing the clinical characteristics of the patients. We identified 409 patients resulting in an annual nationwide incidence of 3.7/100,000. 3.2% of the patients had NF. Similar incidence of invasive GAS infection has been observed worldwide.
The Innovation
This technology is based on the use of a peptide that is produced by GAS itself and is role is to reduce virulence, and thus to facilitate more symbiotic relationships with the host. We demonstrated that a synthetic peptide of this type prevented GAS spreading and led to complete recovery from otherwise lethal infection when injected together with a NF causing strain into mice. We believe that peptides of similar functions exist in Streptococcus pneumoniae, group B streptococci and Staphylococcus aureus, which are the major pathogens of Gram-positive bacteria. Thus, we assume the novel approach can be expanded to other Gram-positive pathogens.
R&D Program
We developed a new in-vivo genetic screen for the identification of genes that are essential for the ability of GAS to cause highly invasive infection. We used a mouse model of human soft-tissue infection that mimics NF in humans, and identified a new locus in a strain isolated from a NF patient.
Future Plans:
We suggest attaining the following aims:
1. To determine which amino acids among the 17 composing the peptide are essential for the protective activity.
2. To test the smallest protective peptide for biosafety and then to perform clinical trials on humans administered with NF.
3. To test the protection induced by the peptide against other Gram-positive pathogens and to identify peptides of similar function in other Gram-positive pathogens.
4. To test the peptides for the ability to prevent bacterial biofilm formation on the surface of various medical devices.
Contact
Yuval Kupitz,
Business Development, Pharmaceuticals
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
