Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection
Enterococcus faecalis is one of the most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. Here, we used a mouse wound excisional model to characterize the infection dynamics of E faecalis and show that infected wounds result in 2 di...
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sg-ntu-dr.10356-893072020-09-21T11:35:44Z Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection Chong, Kelvin Kian Long Tay, Wei Hong Janela, Baptiste Yong, Adeline Mei Hui Liew, Tze Horng Madden, Leigh Keogh, Damien Barkham, Timothy Mark Sebastian Ginhoux, Florent Becker, David Laurence Kline, Kimberly A. School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Singapore Centre for Environmental Life Sciences Engineering NTU Institute for Health Technologies Enterococcus Faecalis Wound Infection Enterococcus faecalis is one of the most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. Here, we used a mouse wound excisional model to characterize the infection dynamics of E faecalis and show that infected wounds result in 2 different states depending on the initial inoculum. Low-dose inocula were associated with short-term, low-titer colonization whereas high-dose inocula were associated with acute bacterial replication and long-term persistence. High-dose infection and persistence were also associated with immune cell infiltration, despite suppression of some inflammatory cytokines and delayed wound healing. During high-dose infection, the multiple peptide resistance factor, which is involved in resisting immune clearance, contributes to E faecalis fitness. These results comprehensively describe a mouse model for investigating E faecalis wound infection determinants, and suggest that both immune modulation and resistance contribute to persistent, nonhealing wounds. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Published version 2018-05-22T03:28:29Z 2019-12-06T17:22:30Z 2018-05-22T03:28:29Z 2019-12-06T17:22:30Z 2017 Journal Article Chong, K. K. L., Tay, W. H., Janela, B., Yong, A. M. H., Liew, T. H., Madden, L., et al. (2017). Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection. Journal of Infectious Diseases, 216(12), 1644-1654. 0022-1899 https://hdl.handle.net/10356/89307 http://hdl.handle.net/10220/44854 10.1093/infdis/jix541 en © 2017 The Author(s) (published by Oxford University Press for the Infectious Diseases Society of America). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 11 p. application/pdf |
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Enterococcus Faecalis Wound Infection |
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Enterococcus Faecalis Wound Infection Chong, Kelvin Kian Long Tay, Wei Hong Janela, Baptiste Yong, Adeline Mei Hui Liew, Tze Horng Madden, Leigh Keogh, Damien Barkham, Timothy Mark Sebastian Ginhoux, Florent Becker, David Laurence Kline, Kimberly A. Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection |
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Enterococcus faecalis is one of the most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. Here, we used a mouse wound excisional model to characterize the infection dynamics of E faecalis and show that infected wounds result in 2 different states depending on the initial inoculum. Low-dose inocula were associated with short-term, low-titer colonization whereas high-dose inocula were associated with acute bacterial replication and long-term persistence. High-dose infection and persistence were also associated with immune cell infiltration, despite suppression of some inflammatory cytokines and delayed wound healing. During high-dose infection, the multiple peptide resistance factor, which is involved in resisting immune clearance, contributes to E faecalis fitness. These results comprehensively describe a mouse model for investigating E faecalis wound infection determinants, and suggest that both immune modulation and resistance contribute to persistent, nonhealing wounds. |
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School of Biological Sciences |
author_facet |
School of Biological Sciences Chong, Kelvin Kian Long Tay, Wei Hong Janela, Baptiste Yong, Adeline Mei Hui Liew, Tze Horng Madden, Leigh Keogh, Damien Barkham, Timothy Mark Sebastian Ginhoux, Florent Becker, David Laurence Kline, Kimberly A. |
format |
Article |
author |
Chong, Kelvin Kian Long Tay, Wei Hong Janela, Baptiste Yong, Adeline Mei Hui Liew, Tze Horng Madden, Leigh Keogh, Damien Barkham, Timothy Mark Sebastian Ginhoux, Florent Becker, David Laurence Kline, Kimberly A. |
author_sort |
Chong, Kelvin Kian Long |
title |
Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection |
title_short |
Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection |
title_full |
Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection |
title_fullStr |
Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection |
title_full_unstemmed |
Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound Infection |
title_sort |
enterococcus faecalis modulates immune activation and slows healing during wound infection |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/89307 http://hdl.handle.net/10220/44854 |
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1681059292125331456 |