Outer Membrane Permeabilization Is an Essential Step in the Killing of Gram-Negative Bacteria by the Lectin RegIIIβ
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| 005 | 20190923032428.0 | ||
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| 024 | 7 | 0 | |a 10.3929/ethz-b-000070973 |2 doi |
| 024 | 7 | 0 | |a 10.1371/journal.pone.0069901 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/70973 | ||
| 100 | 1 | |a Miki |D Tsuyoshi | |
| 245 | 1 | 0 | |a Outer Membrane Permeabilization Is an Essential Step in the Killing of Gram-Negative Bacteria by the Lectin RegIIIβ |h [Elektronische Daten] |c [Tsuyoshi Miki, Wolf-Dietrich; id_orcid 0000-0002-9892-6420 Hardt] |
| 246 | 0 | |a PLoS ONE | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a The C-type lectin RegIIIβ can kill certain Gram-positive and Gram-negative bacteria. The susceptibility of S. Typhimurium depends on the bacterial growth phase, i.e., bacteria from the logarithmic growth phase do bind RegIIIβ and are subsequently killed. Lipid A is one of the bacterial targets for RegIIIβ. However, at the molecular level, it is not understood how RegIIIβ interacts with and kills Gram-negative bacteria. Here, we show that RegIIIβ interacts with Gram-negative bacteria in two distinct steps. Initially, it binds to surface-exposed lipid A. The lipid A can be shielded by the O-antigen of lipopolysaccharide (LPS), as indicated by the exquisite susceptibility of wbaP mutants to RegIIIβ-mediated killing. Increased cell viability after incubation with an anti-lipid A antibody also supports this conclusion. This RegIIIβ-binding permeabilizes the outer membrane to hydrophobic dyes like Ethidium bromide or to bulky bacteriolytic enzymes like lysozyme. Conversely, compromising the outer membrane integrity by the mild detergent Triton X-100 enhances the antibacterial effect of RegIIIβ. Based on our observations, we conclude that RegIIIβ interacts with Gram-negative bacteria in two subsequent steps. Initially, it binds to the outer membrane thus leading to outer membrane permeabilization. This initial step is necessary for RegIIIβ to reach a second, still not well understood target site (presumably localized in the periplasm or the cytoplasmic membrane), thereby triggering bacterial death. This provides novel insights into the outer membrane-step of the bactericidal mechanism of RegIIIβ. | |
| 540 | |a Creative Commons Attribution 3.0 Unported |u http://creativecommons.org/licenses/by/3.0 |2 ethresearch | ||
| 700 | 1 | |a Hardt |D Wolf-Dietrich; id_orcid 0000-0002-9892-6420 |e joint author | |
| 773 | 0 | |t PLoS ONE |d San Francisco, CA, USA : Public Library of Science |g 8 (7), p. e69901 |x 1932-6203 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/70973 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/70973 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 100 |E 1- |a Miki |D Tsuyoshi | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Hardt |D Wolf-Dietrich; id_orcid 0000-0002-9892-6420 |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t PLoS ONE |d San Francisco, CA, USA : Public Library of Science |g 8 (7), p. e69901 |x 1932-6203 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||