Viable gram negative bacteria lacking outer membrane agonists of TLR4/MD-2

US9068186B2 · kind B2 · utility

Assignee

• Research Corporation Technologies, Inc. · US

Inventors

• David Bramhill · Tucson, US
• Uwe Mamat · Hanerau-Hademarschen, DE

Key dates

• Filing date: Mar 11, 2011
• Grant date: Jun 30, 2015
• Expiry date: Dec 21, 2031

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02A50/30
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporters capacity to transport Lipid IVA or in membrane protein YhjD. One or more genes (e.g., IpxL, IpxM, pagP, IpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.