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

Autor: Wong JJ; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.; Singapore Centre for Environmental Life Sciences Engineering, Interdisciplinary Graduate Programme, Nanyang Technological University, Singapore, Singapore., Ho FK; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore., Choo PY; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore., Chong KKL; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.; Nanyang Technological University Institute for Health Technologies, Interdisciplinary Graduate School, Nanyang Technological University, Singapore, Singapore., Ho CMB; School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore., Neelakandan R; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Keogh D; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore., Barkham T; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore., Chen J; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Liu CF; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Kline KA; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Sep 06; Vol. 18 (9), pp. e1010766. Date of Electronic Publication: 2022 Sep 06 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010766
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje