Crossref
journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
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.
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- OmpA – and WT E. coli were passaged twice in 129/Sv mice before use. For each organism at least 20 WT mice were injected ip with varying amounts of bacteria (CFUs) and their survival was followed over time. From these studies the LD 50 from bacteria was determined by interpolation for each bacterial strain. Next 10 NE –/– mice and 10 of their NE +/+ littermates were infected ip and their survival was monitored over time.
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- Single-letter abbreviations for the amino acid residues are as follows: A Ala; D Asp; E Glu; G Gly; I Ile; K Lys; N Asn; P Pro; T Thr; W Trp; and Y Tyr.
- We thank J. Gaither-Ganim J. Campbell and M. Veith for their excellent technical support R. M. Senior and M. Caparon for critical review of the manuscript and A. A. Todorov for statistical analysis. All of the animal experiments were in accordance with Washington University Animal Studies Committee guidelines. This work was supported by a Barnes-Jewish Hospital foundation grant (to A.B.) and by the NIH (to S.D.S. and K.S.K.).
Dates
| Type | When |
|---|---|
| Created | 23 years, 1 month ago (July 27, 2002, 5:40 a.m.) |
| Deposited | 1 year, 7 months ago (Jan. 13, 2024, 4:35 a.m.) |
| Indexed | 6 days, 20 hours ago (Aug. 22, 2025, 12:45 a.m.) |
| Issued | 25 years ago (Aug. 18, 2000) |
| Published | 25 years ago (Aug. 18, 2000) |
| Published Print | 25 years ago (Aug. 18, 2000) |
@article{Belaaouaj_2000, title={Degradation of Outer Membrane Protein A in Escherichia coli Killing by Neutrophil Elastase}, volume={289}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.289.5482.1185}, DOI={10.1126/science.289.5482.1185}, number={5482}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Belaaouaj, Abderr azzaq and Kim, Kwang Sik and Shapiro, Steven D.}, year={2000}, month=aug, pages={1185–1187} }