Protection against Escherichia coli infection by antibody to the Staphylococcus aureus poly- N -acetylglucosamine surface polysaccharide

doi:10.1073/pnas.0700630104

Protection against Escherichia coli infection by antibody to the Staphylococcus aureus poly-N-acetylglucosamine surface polysaccharide

*Channing Laboratory, Brigham and Women's Hospital and
^§Division of Infectious Diseases, Children's Hospital, Harvard Medical School, Boston, MA 02115;
^‡Department of Microbiology, Virginia Commonwealth University, Richmond, VA 23298; and
^†Institute for Biotechnology and Bioengineering, Centre for Biological Engineering, Universidade do Minho, 4700 Braga, Portugal

Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved March 18, 2007 (received for review January 24, 2007)

Abstract

Poly-N-acetylglucosamine (PNAG) is a surface polysaccharide produced by Staphylococcus aureus and Staphyloccus epidermidis and is an effective target for opsonic and protective Ab for these two organisms. Recently, it has been found that Escherichia coli produces an exo-polysaccharide, designated polyglucosamine, that is biochemically indistinguishable from PNAG. We analyzed 30 E. coli strains isolated from urinary tract and neonatal bloodstream infections for the pga locus, PNAG antigen production, and susceptibility to opsonic killing and protection from lethal infection by Ab to PNAG. Twenty-six of 30 strains carried the pga locus, 25 of 30 expressed immunologically detectable PNAG, and 21 of 30 could be killed by rabbit IgG specific for the deacetylated form of the staphylococcal PNAG. Ab to staphylococcal PNAG protected mice against lethality from five different E. coli strains expressing PNAG. PNAG expression by both Gram-negative and Gram-positive organisms could make this antigen a conserved vaccine target for multiple pathogenic species of bacteria.

Footnotes

^¶To whom correspondence should be addressed. E-mail: gpier{at}rics.bwh.harvard.edu
Author contributions: N.C. and T.M.-L. contributed equally to this work; N.C., T.M.-L., K.K.J., and G.B.P. designed research; N.C., T.M.-L., K.K.J., and M.G. performed research; T.M.-L. and K.K.J. contributed new reagents/analytic tools; N.C., T.M.-L., K.K.J., D.A.G., and G.B.P. analyzed data; and N.C., T.M.-L., K.K.J., D.A.G., and G.B.P. wrote the paper.
Conflict of interest statement: T.M.-L., K.K.J., and G.B.P. have filed patents and received royalty/licensing income for development of PNAG as a vaccine.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700630104/DC1.
Abbreviations:

dPNAG,

deacetylated PNAG;

DT,

diphtheria toxoid;

ica,

intercellular adhesin;

NICU,

neonatal intensive care unit;

PGA,

polyglucosamine;

PNAG,

poly-N-acetylglucosamine;

UTI,

urinary tract infection.