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: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-09-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010766 |
| _version_ | 1828105881470894080 |
|---|---|
| author | Jun Jie Wong Foo Kiong Ho Pei Yi Choo Kelvin K L Chong Chee Meng Benjamin Ho Ramesh Neelakandan Damien Keogh Timothy Barkham John Chen Chuan Fa Liu Kimberly A Kline |
| author_facet | Jun Jie Wong Foo Kiong Ho Pei Yi Choo Kelvin K L Chong Chee Meng Benjamin Ho Ramesh Neelakandan Damien Keogh Timothy Barkham John Chen Chuan Fa Liu Kimberly A Kline |
| author_sort | Jun Jie Wong |
| collection | DOAJ |
| 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 | 2024-04-11T10:08:51Z |
| format | Article |
| id | doaj.art-dc72b64de09642fb83abab1bf2c322b6 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-11T10:08:51Z |
| publishDate | 2022-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-dc72b64de09642fb83abab1bf2c322b62022-12-22T04:30:09ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-09-01189e101076610.1371/journal.ppat.1010766Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition.Jun Jie WongFoo Kiong HoPei Yi ChooKelvin K L ChongChee Meng Benjamin HoRamesh NeelakandanDamien KeoghTimothy BarkhamJohn ChenChuan Fa LiuKimberly A KlineWound 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.https://doi.org/10.1371/journal.ppat.1010766 |
| spellingShingle | Jun Jie Wong Foo Kiong Ho Pei Yi Choo Kelvin K L Chong Chee Meng Benjamin Ho Ramesh Neelakandan Damien Keogh Timothy Barkham John Chen Chuan Fa Liu Kimberly A Kline Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition. PLoS Pathogens |
| 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 |
| url | https://doi.org/10.1371/journal.ppat.1010766 |
| work_keys_str_mv | AT junjiewong escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT fookiongho escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT peiyichoo escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT kelvinklchong escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT cheemengbenjaminho escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT rameshneelakandan escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT damienkeogh escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT timothybarkham escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT johnchen escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT chuanfaliu escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition AT kimberlyakline escherichiacolibarauvryregulatesthepksislandandkillsstaphylococciviathegenotoxincolibactinduringinterspeciescompetition |