Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections

Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with in vivo transposon and RNA sequencing approaches, we identified the E. faecalis purine biosynthetic pathway and galactose/mannose MptAB...

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Main Authors: Tan, Casandra Ai Zhu, Chong, Kelvin Kian Long, Yeong, Daryl Yu Xuan, Ng, Celine Hui Min, Muhammad Hafiz Ismail, Yap, Zhei Hwee, Khetrapal, Varnica, Tay, Vanessa Shi Yun, Drautz-Moses, Daniela I., Ali, Yusuf, Chen, Swaine L., Kline, Kimberly A.
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2024
Subjects:
Online Access:https://hdl.handle.net/10356/178572
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author Tan, Casandra Ai Zhu
Chong, Kelvin Kian Long
Yeong, Daryl Yu Xuan
Ng, Celine Hui Min
Muhammad Hafiz Ismail
Yap, Zhei Hwee
Khetrapal, Varnica
Tay, Vanessa Shi Yun
Drautz-Moses, Daniela I.
Ali, Yusuf
Chen, Swaine L.
Kline, Kimberly A.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Tan, Casandra Ai Zhu
Chong, Kelvin Kian Long
Yeong, Daryl Yu Xuan
Ng, Celine Hui Min
Muhammad Hafiz Ismail
Yap, Zhei Hwee
Khetrapal, Varnica
Tay, Vanessa Shi Yun
Drautz-Moses, Daniela I.
Ali, Yusuf
Chen, Swaine L.
Kline, Kimberly A.
author_sort Tan, Casandra Ai Zhu
collection NTU
description Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with in vivo transposon and RNA sequencing approaches, we identified the E. faecalis purine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential for E. faecalis acute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the consumption of purine metabolites by E. faecalis during acute replication and changing carbohydrate availability during the course of wound infection. Overall, our findings reveal the importance of the wound microenvironment in E. faecalis wound pathogenesis and how these metabolic pathways can be targeted to better control wound infections.
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spelling ntu-10356/1785722024-06-27T15:30:20Z Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections Tan, Casandra Ai Zhu Chong, Kelvin Kian Long Yeong, Daryl Yu Xuan Ng, Celine Hui Min Muhammad Hafiz Ismail Yap, Zhei Hwee Khetrapal, Varnica Tay, Vanessa Shi Yun Drautz-Moses, Daniela I. Ali, Yusuf Chen, Swaine L. Kline, Kimberly A. School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Singapore Centre for Environmental Life Sciences and Engineering Medicine, Health and Life Sciences Carbohydrates Fitness determinants Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with in vivo transposon and RNA sequencing approaches, we identified the E. faecalis purine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential for E. faecalis acute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the consumption of purine metabolites by E. faecalis during acute replication and changing carbohydrate availability during the course of wound infection. Overall, our findings reveal the importance of the wound microenvironment in E. faecalis wound pathogenesis and how these metabolic pathways can be targeted to better control wound infections. Ministry of Education (MOE) National Research Foundation (NRF) Published version This work was supported by the National Research Foundation and Ministry of Education Singapore under its Research Centre of Excellence Program and by a grant from the National Medical Research Council (MOH-OFIRG18may-005) awarded to K.A.K. This work was part supported by the Ministry of Education Singapore under its Singapore Ministry of Education Academic Research Fund Tier 1 (2019-T1-001-059) awarded to Y.A. Preparation of this article was also financially supported by the Interdisciplinary Graduate Program of Nanyang Technological University. 2024-06-26T07:58:27Z 2024-06-26T07:58:27Z 2024 Journal Article Tan, C. A. Z., Chong, K. K. L., Yeong, D. Y. X., Ng, C. H. M., Muhammad Hafiz Ismail, Yap, Z. H., Khetrapal, V., Tay, V. S. Y., Drautz-Moses, D. I., Ali, Y., Chen, S. L. & Kline, K. A. (2024). Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections. MBio, 15(1), e0238423-. https://dx.doi.org/10.1128/mbio.02384-23 2150-7511 https://hdl.handle.net/10356/178572 10.1128/mbio.02384-23 38078746 2-s2.0-85182596009 1 15 e0238423 en MOH-OFIRG18may-005 2019-T1-001-059 mBio © 2023 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. application/pdf
spellingShingle Medicine, Health and Life Sciences
Carbohydrates
Fitness determinants
Tan, Casandra Ai Zhu
Chong, Kelvin Kian Long
Yeong, Daryl Yu Xuan
Ng, Celine Hui Min
Muhammad Hafiz Ismail
Yap, Zhei Hwee
Khetrapal, Varnica
Tay, Vanessa Shi Yun
Drautz-Moses, Daniela I.
Ali, Yusuf
Chen, Swaine L.
Kline, Kimberly A.
Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections
title Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections
title_full Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections
title_fullStr Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections
title_full_unstemmed Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections
title_short Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections
title_sort purine and carbohydrate availability drive enterococcus faecalis fitness during wound and urinary tract infections
topic Medicine, Health and Life Sciences
Carbohydrates
Fitness determinants
url https://hdl.handle.net/10356/178572
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