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Enterococcus faecalis modulates immune activation and slows healing during wound infection

Kelvin Kian Long Chong, Wei Hong Tay, Baptiste Janela, Mei Hui Adeline Yong, Tze Horng Liew, Leigh Madden, Damien Keogh, Timothy Mark Sebastian Barkham, Florent Ginhoux, David Laurence Becker, Kimberly A. Kline
doi: https://doi.org/10.1101/125252
Kelvin Kian Long Chong
1Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, SBS-B1n-27, 60 Nanyang Drive, Singapore 637551
2Nanyang Institute of Technology in Health and Medicine (NITHM), Research Techno Plaza, Nanyang Technological University, Frontiers Block #02-07, 50 Nanyang Drive, Singapore 637553
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Wei Hong Tay
1Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, SBS-B1n-27, 60 Nanyang Drive, Singapore 637551
3Singapore Centre for Environmental Life Sciences Engineering, Interdisciplinary Graduate School, Nanyang Technological University, SBS-B2n-27, 60 Nanyang Drive, Singapore 637551
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Baptiste Janela
4Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Singapore 138648
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Mei Hui Adeline Yong
1Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, SBS-B1n-27, 60 Nanyang Drive, Singapore 637551
5School of Biological Sciences, Nanyang Technological University, SBS-B2n-27, 60 Nanyang Drive, Singapore 637551
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Tze Horng Liew
1Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, SBS-B1n-27, 60 Nanyang Drive, Singapore 637551
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Leigh Madden
6Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232
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Damien Keogh
1Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, SBS-B1n-27, 60 Nanyang Drive, Singapore 637551
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Timothy Mark Sebastian Barkham
7Department of Laboratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433
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Florent Ginhoux
4Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Singapore 138648
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David Laurence Becker
6Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232
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Kimberly A. Kline
1Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, SBS-B1n-27, 60 Nanyang Drive, Singapore 637551
4Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Singapore 138648
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  • For correspondence: kkline@ntu.edu.sg
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ABSTRACT

Enterococcus faecalis is one of 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 two 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 (MprF) 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, non-healing wounds.

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Posted April 07, 2017.
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Enterococcus faecalis modulates immune activation and slows healing during wound infection
Kelvin Kian Long Chong, Wei Hong Tay, Baptiste Janela, Mei Hui Adeline Yong, Tze Horng Liew, Leigh Madden, Damien Keogh, Timothy Mark Sebastian Barkham, Florent Ginhoux, David Laurence Becker, Kimberly A. Kline
bioRxiv 125252; doi: https://doi.org/10.1101/125252
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Enterococcus faecalis modulates immune activation and slows healing during wound infection
Kelvin Kian Long Chong, Wei Hong Tay, Baptiste Janela, Mei Hui Adeline Yong, Tze Horng Liew, Leigh Madden, Damien Keogh, Timothy Mark Sebastian Barkham, Florent Ginhoux, David Laurence Becker, Kimberly A. Kline
bioRxiv 125252; doi: https://doi.org/10.1101/125252

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