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Enterococcal PrgA Extends Far Outside the Cell and Provides Surface Exclusion to Protect against Unwanted Conjugation
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2020 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 432, no 20, p. 5681-5695Article in journal (Refereed) Published
Abstract [en]

Horizontal gene transfer between Gram-positive bacteria leads to a rapid spread of virulence factors and antibiotic resistance. This transfer is often facilitated via type 4 secretion systems (T4SS), which frequently are encoded on conjugative plasmids. However, donor cells that already contain a particular conjugative plasmid resist acquisition of a second copy of said plasmid. They utilize different mechanisms, including surface exclusion for this purpose. Enterococcus faecalis PrgA, encoded by the conjugative plasmid pCF10, is a surface protein that has been implicated to play a role in both virulence and surface exclusion, but the mechanism by which this is achieved has not been fully explained. Here, we report the structure of full-length PrgA, which shows that PrgA protrudes far out from the cell wall (approximately 40 nm), where it presents a protease domain. In vivo experiments show that PrgA provides a physical barrier to cellular adhesion, thereby reducing cellular aggregation. This function of PrgA contributes to surface exclusion, reducing the uptake of its cognate plasmid by approximately one order of magnitude. Using variants of PrgA with mutations in the catalytic site we show that the surface exclusion effect is dependent on the activity of the protease domain of PrgA. In silico analysis suggests that PrgA can interact with another enterococcal adhesin, PrgB, and that these two proteins have co-evolved. PrgB is a strong virulence factor, and PrgA is involved in post-translational processing of PrgB. Finally, competition mating experiments show that PrgA provides a significant fitness advantage to plasmid-carrying cells. 

Place, publisher, year, edition, pages
Elsevier, 2020. Vol. 432, no 20, p. 5681-5695
National Category
Microbiology in the medical area Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-176149DOI: 10.1016/j.jmb.2020.08.018ISI: 000576472300011PubMedID: 32860774Scopus ID: 2-s2.0-85090485292OAI: oai:DiVA.org:umu-176149DiVA, id: diva2:1478499
Funder
Swedish Research Council, 2016-03599Knut and Alice Wallenberg FoundationThe Kempe Foundations, JCK-1524The Kempe Foundations, SMK-1869NIH (National Institute of Health), R35 GM118079Available from: 2020-10-22 Created: 2020-10-22 Last updated: 2024-07-02Bibliographically approved

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Schmitt, AndreasJärvå, Michael A.Sun, Wei-Shengter Beek, JosyBerntsson, Ronnie Per-Arne

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Schmitt, AndreasJärvå, Michael A.Sun, Wei-Shengter Beek, JosyBerntsson, Ronnie Per-Arne
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Department of Medical Biochemistry and BiophysicsWallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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Journal of Molecular Biology
Microbiology in the medical areaBiochemistry and Molecular Biology

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