학술논문
Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria
Document Type
Original Paper
Author
Mu, Andre; Klare, William P.; Baines, Sarah L.; Ignatius Pang, C. N.; Guérillot, Romain; Harbison-Price, Nichaela; Keller, Nadia; Wilksch, Jonathan; Nhu, Nguyen Thi Khanh; Phan, Minh-Duy; Keller, Bernhard; Nijagal, Brunda; Tull, Dedreia; Dayalan, Saravanan; Chua, Hwa Huat Charlie; Skoneczny, Dominik; Koval, Jason; Hachani, Abderrahman; Shah, Anup D.; Neha, Nitika; Jadhav, Snehal; Partridge, Sally R.; Cork, Amanda J.; Peters, Kate; Bertolla, Olivia; Brouwer, Stephan; Hancock, Steven J.; Álvarez-Fraga, Laura; De Oliveira, David M. P.; Forde, Brian; Dale, Ashleigh; Mujchariyakul, Warasinee; Walsh, Calum J.; Monk, Ian; Fitzgerald, Anna; Lum, Mabel; Correa-Ospina, Carolina; Roy Chowdhury, Piklu; Parton, Robert G.; De Voss, James; Beckett, James; Monty, Francois; McKinnon, Jessica; Song, Xiaomin; Stephen, John R.; Everest, Marie; Bellgard, Matt I.; Tinning, Matthew; Leeming, Michael; Hocking, Dianna; Jebeli, Leila; Wang, Nancy; Ben Zakour, Nouri; Yasar, Serhat A.; Vecchiarelli, Stefano; Russell, Tonia; Zaw, Thiri; Chen, Tyrone; Teng, Don; Kassir, Zena; Lithgow, Trevor; Jenney, Adam; Cole, Jason N.; Nizet, Victor; Sorrell, Tania C.; Peleg, Anton Y.; Paterson, David L.; Beatson, Scott A.; Wu, Jemma; Molloy, Mark P.; Syme, Anna E.; Goode, Robert J. A.; Hunter, Adam A.; Bowland, Grahame; West, Nicholas P.; Wilkins, Marc R.; Djordjevic, Steven P.; Davies, Mark R.; Seemann, Torsten; Howden, Benjamin P.; Pascovici, Dana; Tyagi, Sonika; Schittenhelm, Ralf B.; De Souza, David P.; McConville, Malcolm J.; Iredell, Jonathan R.; Cordwell, Stuart J.; Strugnell, Richard A.; Stinear, Timothy P.; Schembri, Mark A.; Walker, Mark J.
Source
Nature Communications. 14(1)
Subject
Language
English
ISSN
2041-1723
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.
Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.
Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.