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

A Mu; WP Klare; SL Baines; CN Ignatius Pang; R Guérillot; N Harbison-Price; N Keller; J Wilksch; NTK Nhu; MD Phan; B Keller; B Nijagal; D Tull; S Dayalan; HHC Chua; D Skoneczny; J Koval; A Hachani; AD Shah; N Neha; S Jadhav; SR Partridge; AJ Cork; K Peters; O Bertolla; S Brouwer; SJ Hancock; L Álvarez-Fraga; DMP De Oliveira; B Forde; A Dale; W Mujchariyakul; CJ Walsh; I Monk; A Fitzgerald; M Lum; C Correa-Ospina; P Roy Chowdhury; RG Parton; J De Voss; J Beckett; F Monty; J McKinnon; X Song; JR Stephen; M Everest; MI Bellgard; M Tinning; M Leeming; D Hocking; L Jebeli; N Wang; N Ben Zakour; SA Yasar; S Vecchiarelli; T Russell; T Zaw; T Chen; D Teng; Z Kassir; T Lithgow; A Jenney; JN Cole; V Nizet; TC Sorrell; AY Peleg; DL Paterson; SA Beatson; J Wu; MP Molloy; AE Syme; RJA Goode; AA Hunter; G Bowland; NP West; MR Wilkins; SP Djordjevic; MR Davies; T Seemann; BP Howden; D Pascovici; S Tyagi; RB Schittenhelm; DP De Souza; MJ McConville; JR Iredell; SJ Cordwell; RA Strugnell; TP Stinear; MA Schembri; MJ Walker

Journal article

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

A Mu, WP Klare, SL Baines, CN Ignatius Pang, R Guérillot, N Harbison-Price, N Keller, J Wilksch, NTK Nhu, MD Phan, B Keller, B Nijagal, D Tull, S Dayalan, HHC Chua, D Skoneczny, J Koval, A Hachani, AD Shah, N Neha Show all

Nature Communications | NATURE PORTFOLIO | Published : 2023

DOI: 10.1038/s41467-023-37200-w

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 l..

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University of Melbourne Researchers

Sarah Baines Author

Romain Guérillot Author

Jonathan Wilksch Author

Brunda Nijagal Author

Grants

Awarded by Bioplatforms Australia

Funding Acknowledgements

The authors thank Bioplatforms Australia and the National Health and Medical Research Council (NHMRC) of Australia for supporting this study. We would like to acknowledge the contribution of the Antibiotic Resistant Sepsis Pathogens Framework Initiative consortium. (https://data.bioplatforms.com/organization/pages/bpa-sepsis/consortium) in the generation of data used in this publication. This work was supported by the Wellcome Trust grant 220540/Z/20/A. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The Initiative is supported by funding from Bioplatforms Australia (enabled by NCRIS). AGRF is supported by the Australian Government National Collaborative Research Infrastructure Initiative through Bioplatforms Australia. C.N.I.P. and M.R.W. acknowledge support from the New South Wales State Government RAAP Scheme. Microscopy was performed at the Australian Cancer Research Foundation (ACRF)/Institute for Molecular Bioscience Cancer Biology Imaging Facility, which was established with the support of the ACRF. The authors would like to acknowledge Peter Pham and Belinda Roychoudhry for expert technical assistance, and Johan Gustafsson for assistance with MetaboLights repository.