Staphylococcal Phage2638A endolysin amidase domain is lytic for Staphylococcus aureus

US9206411B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Secretary of Agriculture · US

Inventors

• David M. Donovan · Baltimore, US
• Igor V. Abaev · Наркевичі, UA

Key dates

• Filing date: Jun 13, 2012
• Grant date: Dec 8, 2015
• Expiry date: Jun 13, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2795/10333
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Staphylococcus aureus is notorious for developing resistance to virtually all antibiotics to which it is exposed. Staphylococcal phage 2638A endolysin is a peptidoglycan hydrolase that is lytic for S. aureus when exposed externally, making it a new antimicrobial candidate. It shares a common protein organization with over 40 other staphylococcal peptidoglycan hydrolases: a CHAP endopeptidase domain, a mid-protein amidase 2 domain and a C-terminal SH3b cell wall binding domain. It is the first phage endolysin reported with a cryptic translational start site between the CHAP and amidase domains. Deletion analysis indicates that the amidase domain confers most of the lytic activity and requires the full SH3b domain for maximal activity. It is common for one domain to demonstrate dominant activity over another; however, the phage 2638A endolysin is the first to show high amidase domain activity dominant over the N-terminal CHAP domain, an important finding for targeting novel peptidoglycan bonds.