Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria
Andre Mu, William P. Klare, Sarah L. Baines, Chi Nam Ignatius Pang, Romain Guérillot, Nichaela Harbison-Price, Nadia Keller, Jonathan J. 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 M. Peters, Olivia M. Bertolla, Stephan Brouwer, Steven J. Hancock, Laura Álvarez-Fraga, David M. P. De Oliveira, Brian M. Forde, Ashleigh Dale, Warasinee Mujchariyakul, Calum J. Walsh, Ian R. Monk, Anna Fitzgerald, Mabel Lum, Carolina Correa-Ospina, Piklu Roy Chowdhury, Robert G. Parton, James J. De Voss, J. B. Beckett, Francois Monty, Jessica McKinnon, Xiaomin Song, J. Stephen, Marie Everest, M. Bellgard, Matthew Tinning, Michael G. Leeming, Dianna M. Hocking, Leila Jebeli, Nancy Wang, Nouri L. 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 Syme, Robert J. A. Goode, Adam 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
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.