Degradation of Outer Membrane Protein A in Escherichia coli Killing by Neutrophil Elastase

Author:

Belaaouaj Abderr azzaq1,Kim Kwang Sik2,Shapiro Steven D.134

Affiliation:

1. Department of Pediatrics,

2. Division of Infectious Diseases, Children's Hospital, Los Angeles, CA 90027, USA.

3. Department of Medicine, and

4. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

In determining the mechanism of neutrophil elastase (NE)–mediated killing of Escherichia coli , we found that NE degraded outer membrane protein A (OmpA), localized on the surface of Gram-negative bacteria. NE killed wild-type, but not OmpA-deficient, E. coli . Also, whereas NE-deficient mice had impaired survival in response to E. coli sepsis, as compared to wild-type mice, the presence or absence of NE had no influence on survival in response to sepsis that had been induced with OmpA-deficient E. coli . These findings define a mechanism of nonoxidative bacterial killing by NE and point to OmpA as a bacterial target in host defense.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference27 articles.

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2. Ganz T., Proc. Assoc. Am. Physicians 111, 390 (1999).

3. J. Blondin A. Janoff J. C. Powers in Neutral Proteases of Human Polymorphonuclear Leukocytes J. Havemann and A. Janoff Eds. (Urban and Schwartzenberg Baltimore MD 1978) pp. 39–55.

4. Zimmer M., et al., Proc. Natl. Acad. Sci. U.S.A. 89, 8215 (1992).

5. Belaaouaj A., et al., Nature Med. 4, 615 (1998).

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