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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481169/ https://www.ncbi.nlm.nih.gov/pubmed/36067266 http://dx.doi.org/10.1371/journal.ppat.1010766 |
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author | Wong, Jun Jie Ho, Foo Kiong Choo, Pei Yi Chong, Kelvin K. L. Ho, Chee Meng Benjamin Neelakandan, Ramesh Keogh, Damien Barkham, Timothy Chen, John Liu, Chuan Fa Kline, Kimberly A. |
author_facet | Wong, Jun Jie Ho, Foo Kiong Choo, Pei Yi Chong, Kelvin K. L. Ho, Chee Meng Benjamin Neelakandan, Ramesh Keogh, Damien Barkham, Timothy Chen, John Liu, Chuan Fa Kline, Kimberly A. |
author_sort | Wong, Jun Jie |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9481169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-94811692022-09-17 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 K. L. Ho, Chee Meng Benjamin Neelakandan, Ramesh Keogh, Damien Barkham, Timothy Chen, John Liu, Chuan Fa Kline, Kimberly A. PLoS Pathog Research Article 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. Public Library of Science 2022-09-06 /pmc/articles/PMC9481169/ /pubmed/36067266 http://dx.doi.org/10.1371/journal.ppat.1010766 Text en © 2022 Wong et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Wong, Jun Jie Ho, Foo Kiong Choo, Pei Yi Chong, Kelvin K. L. Ho, Chee Meng Benjamin 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 | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481169/ https://www.ncbi.nlm.nih.gov/pubmed/36067266 http://dx.doi.org/10.1371/journal.ppat.1010766 |
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