Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition.

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: PLoS Pathogens, Vol 18, Iss 9, p e1010766 (2022)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1010766
Popis: 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.
Databáze: Directory of Open Access Journals
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