Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections
Enterococcus faecalis is an opportunistic pathogen that is frequently co-isolated with other microbes in wound infections. While E. faecalis can subvert the host immune response and promote the survival of other microbes via interbacterial synergy, little is known about the impact of E. faecalis-med...
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sg-ntu-dr.10356-1739812024-03-11T15:32:27Z Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections Kao, Patrick Hsien-Neng Ch'ng, Jun-Hong Chong, Kelvin Kian Long Stocks, Claudia J. Wong, Siu Ling Kline, Kimberly A. School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Tan Tock Seng Hospital Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) Medicine, Health and Life Sciences Enterococcus faecalis Staphylococcus aureus Enterococcus faecalis is an opportunistic pathogen that is frequently co-isolated with other microbes in wound infections. While E. faecalis can subvert the host immune response and promote the survival of other microbes via interbacterial synergy, little is known about the impact of E. faecalis-mediated immune suppression on co-infecting microbes. We hypothesized that E. faecalis can attenuate neutrophil-mediated responses in mixed-species infection to promote survival of the co-infecting species. We found that neutrophils control E. faecalis infection via phagocytosis, ROS production, and degranulation of azurophilic granules, but it does not trigger neutrophil extracellular trap formation (NETosis). However, E. faecalis attenuates Staphylococcus aureus-induced NETosis in polymicrobial infection by interfering with citrullination of histone, suggesting E. faecalis can actively suppress NETosis in neutrophils. Residual S. aureus-induced NETs that remain during co-infection do not impact E. faecalis, further suggesting that E. faecalis possess mechanisms to evade or survive NET-associated killing mechanisms. E. faecalis-driven reduction of NETosis corresponds with higher S. aureus survival, indicating that this immunomodulating effect could be a risk factor in promoting the virulence polymicrobial infection. These findings highlight the complexity of the immune response to polymicrobial infections and suggest that attenuated pathogen-specific immune responses contribute to pathogenesis in the mammalian host. Ministry of Education (MOE) National Research Foundation (NRF) Published version This work was carried out at the Singapore Centre for Environmental and Life Science Engineering (SCELSE), whose research is supported by the National Research Foundation Singapore, Ministry of Education, to Nanyang Technological University and the National University of Singapore under its Research Centre of Excellence Programme. This work was funded by a Singapore Ministry of Education Academic Research Fund Tier 2 Grant awarded to K.A.K. (MOE2019-T2-2-089). 2024-03-08T07:56:17Z 2024-03-08T07:56:17Z 2023 Journal Article Kao, P. H., Ch'ng, J., Chong, K. K. L., Stocks, C. J., Wong, S. L. & Kline, K. A. (2023). Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections. FEMS Microbes, 4, xtad019-. https://dx.doi.org/10.1093/femsmc/xtad019 2633-6685 https://hdl.handle.net/10356/173981 10.1093/femsmc/xtad019 37900578 2-s2.0-85178303068 4 xtad019 en MOE2019-T2-2-089 FEMS Microbes © 2023 The Author(s). Published by Oxford University Press on behalf of FEMS. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com application/pdf |
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Medicine, Health and Life Sciences Enterococcus faecalis Staphylococcus aureus Kao, Patrick Hsien-Neng Ch'ng, Jun-Hong Chong, Kelvin Kian Long Stocks, Claudia J. Wong, Siu Ling Kline, Kimberly A. Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections |
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Enterococcus faecalis is an opportunistic pathogen that is frequently co-isolated with other microbes in wound infections. While E. faecalis can subvert the host immune response and promote the survival of other microbes via interbacterial synergy, little is known about the impact of E. faecalis-mediated immune suppression on co-infecting microbes. We hypothesized that E. faecalis can attenuate neutrophil-mediated responses in mixed-species infection to promote survival of the co-infecting species. We found that neutrophils control E. faecalis infection via phagocytosis, ROS production, and degranulation of azurophilic granules, but it does not trigger neutrophil extracellular trap formation (NETosis). However, E. faecalis attenuates Staphylococcus aureus-induced NETosis in polymicrobial infection by interfering with citrullination of histone, suggesting E. faecalis can actively suppress NETosis in neutrophils. Residual S. aureus-induced NETs that remain during co-infection do not impact E. faecalis, further suggesting that E. faecalis possess mechanisms to evade or survive NET-associated killing mechanisms. E. faecalis-driven reduction of NETosis corresponds with higher S. aureus survival, indicating that this immunomodulating effect could be a risk factor in promoting the virulence polymicrobial infection. These findings highlight the complexity of the immune response to polymicrobial infections and suggest that attenuated pathogen-specific immune responses contribute to pathogenesis in the mammalian host. |
author2 |
School of Biological Sciences |
author_facet |
School of Biological Sciences Kao, Patrick Hsien-Neng Ch'ng, Jun-Hong Chong, Kelvin Kian Long Stocks, Claudia J. Wong, Siu Ling Kline, Kimberly A. |
format |
Article |
author |
Kao, Patrick Hsien-Neng Ch'ng, Jun-Hong Chong, Kelvin Kian Long Stocks, Claudia J. Wong, Siu Ling Kline, Kimberly A. |
author_sort |
Kao, Patrick Hsien-Neng |
title |
Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections |
title_short |
Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections |
title_full |
Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections |
title_fullStr |
Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections |
title_full_unstemmed |
Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections |
title_sort |
enterococcus faecalis suppresses staphylococcus aureus-induced netosis and promotes bacterial survival in polymicrobial infections |
publishDate |
2024 |
url |
https://hdl.handle.net/10356/173981 |
_version_ |
1794549405718675456 |