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Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection

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Title: Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection
Authors: Siggins, MK
Lynskey, NN
Lamb, L
Johnson, L
Huse, K
Pearson, M
Banerji, S
Turner, CE
Woollard, K
Jackson, DG
Sriskandan, S
Item Type: Journal Article
Abstract: Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack lymphatic vessels to escape a local infection site, transiting through sequential lymph nodes and efferent lymphatic vessels to enter the bloodstream. Contrasting with previously reported mechanisms of intracellular pathogen carriage by phagocytes, we show S. pyogenes remain extracellular during transit, first in afferent and then efferent lymphatics that carry the bacteria through successive draining lymph nodes. We identify streptococcal virulence mechanisms important for bacterial lymphatic dissemination and show that metastatic streptococci within infected lymph nodes resist and subvert clearance by phagocytes, enabling replication that can seed intense bloodstream infection. The findings establish the lymphatic system as both a survival niche and conduit to the bloodstream for S. pyogenes, explaining the phenomenon of occult bacteraemia. This work provides new perspectives in streptococcal pathogenesis with implications for immunity.
Issue Date: 17-Sep-2020
Date of Acceptance: 24-Aug-2020
URI: http://hdl.handle.net/10044/1/82630
DOI: 10.1038/s41467-020-18454-0
ISSN: 2041-1723
Publisher: Nature Research
Journal / Book Title: Nature Communications
Volume: 11
Copyright Statement: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Wellcome Trust
Medical Research Council (MRC)
Funder's Grant Number: 103197/Z/13/Z
MR/L008610/1
Publication Status: Published
Article Number: ARTN 4697
Appears in Collections:Department of Immunology and Inflammation
Department of Infectious Diseases
National Heart and Lung Institute



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