Bioinformatic method for identifying surface-anchored proteins from gram-positive bacteria and proteins obtained thereby

• US 7,615,616 B2
• Filed: 09/15/2003
• Issued: 11/10/2009
• Est. Priority Date: 09/13/2002
• Status: Active Grant

• Current Assignee: Inhibitex Incorporated (Bristol-Myers Squibb Company), Texas A&M University System, UAB Research Foundation (University of Alabama System)
• Original Assignee: Inhibitex Incorporated (Bristol-Myers Squibb Company), Texas A&M University System, UAB Research Foundation (University of Alabama System)
• Inventors: Xu, Yi, Hook, Magnus, Hutchins, Jeff T., Patti, Joseph M., Bowden, Maria G., Sthanam, Narayana, Hall, Andrea, Ponnuraj, Karthe, Sillanpaa, Jouko V.
• Primary Examiner(s): Graser; Jennifer E
• Application Number:
  US10/661,809
• Publication Number:
  US 20040101919A1
• Time in Patent Office: 2,248 Days
• Field of Search: 530/387.1, 530/388.1, 435/243, 435/975, 424/130.1, 424/133.1, 424/139.1, 424/141.1, 424/150.1, 424/164.1
• US Class Current: 530/387.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/315 from Streptococcus (G), e.g. Enterococci
• CPC Class Codes: C07K 16/1267 from Gram-positive bacteria
• CPC Class Codes: G01N 33/56911 Bacteria
• CPC Class Codes: G01N 33/56916 Enterobacteria, e.g. shigella, salmonella, klebsiella, serratia
• CPC Class Codes: G16B 15/00 ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• CPC Class Codes: G16B 15/20 Protein or domain folding
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 435/975 Kit

Abstract

A bioinformatic method is provided for identifying and isolating proteins with MSCRAMM®—like characteristics from Gram positive bacteria, such as Enterococcus, Staphylococcus, Streptococcus and Bacillus bacteria, which can then be utilized in methods to prevent and treat infections caused by Gram-positive bacteria. The method involves identifying from sequence information those proteins with a putative C-terminal LPXTG (SEQ ID NO:1) cell wall sorting signal and other structural similarities to MSCRAMM® proteins having the LPXTG-anchored cell wall proteins. The MSCRAMM® proteins and immunogenic regions therein that are identified and isolated using the present invention may be used to generate antibodies useful in the diagnosis, treatment or prevention of Gram positive bacterial infections.

Claims

1. An isolated antibody capable of binding to an amino acid sequence consisting of amino acids 33-592 of SEQ ID NO:

13.

2. The antibody according to claim 1 wherein the antibody is a monoclonal antibody.

3. The antibody according to claim 1 selected from the group consisting of single chain, chimeric, murine, humanized and human monoclonal antibodies.

4. The antibody according to claim 1, wherein said antibody treats an E. faecalis bacterial infection in a human or animal.

5. The antibody according to claim 1, wherein said antibody is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.

6. Isolated antisera containing an antibody according to claim 1.

7. A diagnostic kit comprising an antibody according to claim 1 and means for detecting binding by that antibody.

8. A diagnostic kit according to claim 7 wherein said means for detecting binding comprises a detectable label that is linked to said antibody.

9. A pharmaceutical composition comprising an effective amount of the antibody of claim 1 and a pharmaceutically acceptable vehicle, carrier or excipient.

10. The antibody according to claim 1, wherein the antibody is a polyclonal antibody.