Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition
Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/170990 |
| _version_ | 1826118585491128320 |
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| author | Wong, Jun Jie Ho, Foo Kiong Choo, Pei Yi Chong, Kelvin Kian Long Ho, Benjamin Chee Meng Neelakandan, Ramesh Keogh, Damien Barkham, Timothy Chen, John Liu, Chuan Fa Kline, Kimberly A. |
| author2 | Interdisciplinary Graduate School (IGS) |
| author_facet | Interdisciplinary Graduate School (IGS) Wong, Jun Jie Ho, Foo Kiong Choo, Pei Yi Chong, Kelvin Kian Long Ho, Benjamin Chee Meng Neelakandan, Ramesh Keogh, Damien Barkham, Timothy Chen, John Liu, Chuan Fa Kline, Kimberly A. |
| author_sort | Wong, Jun Jie |
| collection | NTU |
| description | Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E. coli wound infection isolates. While it is not clear how colibactin is released from E. coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S. aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E. coli and S. aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition. |
| first_indexed | 2024-10-01T04:46:12Z |
| format | Journal Article |
| id | ntu-10356/170990 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:46:12Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1709902023-10-12T15:30:22Z Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition Wong, Jun Jie Ho, Foo Kiong Choo, Pei Yi Chong, Kelvin Kian Long Ho, Benjamin Chee Meng Neelakandan, Ramesh Keogh, Damien Barkham, Timothy Chen, John Liu, Chuan Fa Kline, Kimberly A. Interdisciplinary Graduate School (IGS) School of Mechanical and Aerospace Engineering School of Biological Sciences Singapore Centre for Environmental Life Sciences and Engineering NTU Institute for Health Technologies Science::Biological sciences Complete Genome Sequence Virulence Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E. coli wound infection isolates. While it is not clear how colibactin is released from E. coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S. aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E. coli and S. aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition. 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 Programme, by the Ministry of Education Singapore under its tier 2 program (MOE2014-T2-01 (K.A.K). 2023-10-10T02:22:12Z 2023-10-10T02:22:12Z 2022 Journal Article Wong, J. J., Ho, F. K., Choo, P. Y., Chong, K. K. L., Ho, B. C. M., Neelakandan, R., Keogh, D., Barkham, T., Chen, J., Liu, C. F. & Kline, K. A. (2022). Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition. PLoS Pathogens, 18(9), e1010766-. https://dx.doi.org/10.1371/journal.ppat.1010766 1553-7366 https://hdl.handle.net/10356/170990 10.1371/journal.ppat.1010766 36067266 2-s2.0-85138297986 9 18 e1010766 en MOE2014-T2-01 PLoS Pathogens © 2022 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf |
| spellingShingle | Science::Biological sciences Complete Genome Sequence Virulence Wong, Jun Jie Ho, Foo Kiong Choo, Pei Yi Chong, Kelvin Kian Long Ho, Benjamin Chee Meng Neelakandan, Ramesh Keogh, Damien Barkham, Timothy Chen, John Liu, Chuan Fa Kline, Kimberly A. Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition |
| title | Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition |
| title_full | Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition |
| title_fullStr | Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition |
| title_full_unstemmed | Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition |
| title_short | Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition |
| title_sort | escherichia coli bara uvry regulates the pks island and kills staphylococci via the genotoxin colibactin during interspecies competition |
| topic | Science::Biological sciences Complete Genome Sequence Virulence |
| url | https://hdl.handle.net/10356/170990 |
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