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

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37200-w

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