Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Andre Mu, William P. Klare, Sarah L. Baines, C. N. Ignatius Pang, Romain Guérillot, Nichaela Harbison-Price, Nadia Keller, Jonathan Wilksch, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Bernhard Keller, Brunda Nijagal, Dedreia Tull, Saravanan Dayalan, Hwa Huat Charlie Chua, Dominik Skoneczny, Jason Koval, Abderrahman Hachani, Anup D. Shah, Nitika NehaSnehal Jadhav, Sally R. Partridge, Amanda J. Cork, Kate Peters, Olivia Bertolla, Stephan Brouwer, Steven J. Hancock, Laura Álvarez-Fraga, David M. P. De Oliveira, Brian Forde, Ashleigh Dale, Warasinee Mujchariyakul, Calum J. Walsh, Ian Monk, Anna Fitzgerald, Mabel Lum, Carolina Correa-Ospina, Piklu Roy Chowdhury, Robert G. Parton, James De Voss, James Beckett, Francois Monty, Jessica McKinnon, Xiaomin Song, John R. Stephen, Marie Everest, Matt I. Bellgard, Matthew Tinning, Michael Leeming, Dianna Hocking, Leila Jebeli, Nancy Wang, Nouri Ben Zakour, Serhat A. Yasar, Stefano Vecchiarelli, Tonia Russell, Thiri Zaw, Tyrone Chen, Don Teng, Zena Kassir, Trevor Lithgow, Adam Jenney, Jason N. Cole, Victor Nizet, Tania C. Sorrell, Anton Y. Peleg, David L. Paterson, Scott A. Beatson, Jemma Wu, Mark P. Molloy, Anna E. Syme, Robert J. A. Goode, Adam A. Hunter, Grahame Bowland, Nicholas P. West, Marc R. Wilkins, Steven P. Djordjevic, Mark R. Davies, Torsten Seemann, Benjamin P. Howden, Dana Pascovici, Sonika Tyagi, Ralf B. Schittenhelm, David P. De Souza, Malcolm J. McConville, Jonathan R. Iredell, Stuart J. Cordwell, Richard A. Strugnell, Timothy P. Stinear, Mark A. Schembri, Mark J. Walker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
17 Downloads (Pure)

Abstract

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20–40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.

Original languageEnglish
Article number1530
Pages (from-to)1-21
Number of pages21
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 18 Mar 2023

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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