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Cross-reactive monoclonal and polyclonal antibodies which recognize surface proteins from coagulase-negative staphylococci and staphylococcus aureus

a staphylococcus, coagulase-negative technology, applied in the field of staphylococcus aureus surface proteins, can solve the problems of remained a significant problem in developing antibodies that exhibit cross-reactivity across the different types, and dramatically alter the physiology of the staphylococcus, so as to prevent or treat the infection of the staphylococcus

Inactive Publication Date: 2005-05-19
FOSTER TIMOTHY +5
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008] It is still further an object of the present invention to provide isolated antibodies that can recognize the A domain of surface proteins such as the DgsK protein from coagulase-negative staphylococci and at the same time recognize surface proteins such as the SasA protein from Staphylococcus aureus.

Problems solved by technology

Once the bacteria have successfully adhered and colonized host tissues, their physiology is dramatically altered and damaging components such as toxins and proteolytic enzymes are secreted.
However, because antibodies by nature are very specific and in the case of different types of Staphylococci, such as S. aureus on one hand (coagulase-positive) and S. epidermidis and S. hemolyticus on the other (coagulase-negative), it has still remained a significant problem to develop antibodies that exhibit cross-reactivity across the different types of bacter

Method used

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  • Cross-reactive monoclonal and polyclonal antibodies which recognize surface proteins from coagulase-negative staphylococci and staphylococcus aureus
  • Cross-reactive monoclonal and polyclonal antibodies which recognize surface proteins from coagulase-negative staphylococci and staphylococcus aureus
  • Cross-reactive monoclonal and polyclonal antibodies which recognize surface proteins from coagulase-negative staphylococci and staphylococcus aureus

Examples

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Effect test

example 1

Isolation and Sequencing of MSCRAMM's from S. Aureus

[0052]Staphylococcus aureus is known to express a class of surface-associated proteins which play important roles in pathogenicity by allowing bacteria to avoid host defenses and by acting as adhesins. These proteins are known as MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) and in most cases are covalently anchored to the cell wall peptidoglycan. They have several common features: (i) an N-terminal signal peptide (approximately 40 residues in length) required for Sec-dependent secretion, (ii) a wall spanning domain either rich in proline and glycine residues or composed of serine and aspartate dipeptide repeats, (iii) an LPXTG motif required for covalent anchoring of the protein to the pentaglycine crossbridge in peptidoglycan, (iv) a hydrophobic membrane-spanning domain followed by (v) several positively charged residues.

[0053] By exploiting the whole genome sequences of S. aureus, eight novel op...

example 2

Isolation and Sequencing of Cross-Reactive Proteins from S. Aureus and from Coagulase-Negative Staphylococci

[0072] It has been recently shown that S. epidermidis contains surface proteins structurally related to S. aureus MSCRAMM® proteins (U.S. Ser. No. 09 / 386,962). One protein from S. aureus is of particular interest since it has a close homologue in S. epidermidis. The protein is called DsqA or SasA (S. aureus) and DgsK (S. epidermidis). They are characterized by a typical “A” domain of approximately 500 amino acid residues, followed by two B repeats of 88 residues that are ˜40% identical, and a unique SXSX dipeptide repeat that can vary in length depending on the strain. Contained within the A domain of the S. aureus DsqA / SasA is a 180 residue region that has ˜40% identity to a similar sized domain within region A of S. aureus proteins RrkN, Pls and S. epidermidis protein Aap The A regions of the DsqA / SasA and DgsK proteins are 46% identical at the amino acid level, the BB repe...

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Abstract

Polyclonal and monoclonal antibodies which are cross-reactive to both coagulase-positive staphylococcus bacteria, such as S. aureus and to coagulase-negative bacteria, such as S. epidermidis and S. hemolyticus, are provided which can recognize surface proteins from both coagulase-positive and coagulase negative staph bacteria. The antibodies may be generated from surface proteins that have been isolated on the basis of characteristics that may be common between S. aureus and coagulase-negative staphylococci, and these recombinant surface proteins are used to generate the antibodies of the invention. There is also provided vaccines and methods which utilize these proteins and antibodies for the treatment or protection against a wide variety of staphylococcal infections.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present application claims the benefit of U.S. provisional application Ser. No. 60 / 298,098 filed Jun. 15, 2001.FIELD OF THE INVENTION [0002] The present invention relates in general to surface proteins from Staphylococcus aureus and their active regions such as their A domains which have homologue proteins on coagulase-negative Staphylococci such as S. epidermidis and S. hemolyticus as well as antibodies which recognize said proteins, and in particular to isolated monoclonal and polyclonal antibodies which recognize specific proteins from Staphylococcus aureus and coagulase-negative Staphylococci and which are cross-reactive against S. aureus and coagulase-negative Staphylococci and can thus be utilized in vaccines and methods useful for preventing or treating a wide variety of infections caused by staphylococcal bacteria. BACKGROUND OF THE INVENTION [0003] The successful colonization of the host is a process required for most micro...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00A61K39/395A61K39/40G01N33/53A61P31/04C07K14/31C07K16/12C12P21/08G01N33/569
CPCC07K16/1271A61P31/04
Inventor FOSTER, TIMOTHYROCHE, FIONAPALLEN, MARKPATTI, JOSEPHHUTCHINS, JEFFSPEZIALE, PIETRO
Owner FOSTER TIMOTHY
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