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

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Mu, A., Klare, W. P., Baines, S. L., Ignatius Pang, C. N., Guérillot, R., Harbison-Price, N., Keller, N., Wilksch, J., Nhu, N. T. K., Phan, M-D., Keller, B., Nijagal, B., Tull, D., Dayalan, S., Chua, H. H. C., Skoneczny, D., Koval, J., Hachani, A., Shah, A. D., Neha, N., Jadhav, S., Partridge, S. R., Cork, A. J., Peters, K., Bertolla, O., Brouwer, S., Hancock, S. J., Álvarez-Fraga, L., De Oliveira, D. M. P., Forde, B., Dale, A., Mujchariyakul, W., Walsh, C. J., Monk, I., Fitzgerald, A., Lum, M., Correa-Ospina, C., Roy Chowdhury, P., Parton, R. G., De Voss, J., Beckett, J., Monty, F., McKinnon, J., Song, X., Stephen, J. R., Everest, M., Bellgard, M. I., Tinning, M., Leeming, M., Hocking, D., Jebeli, L., Wang, N., Ben Zakour, N., Yasar, S. A., Vecchiarelli, S., Russell, T., Zaw, T., Chen, T., Teng, D., Kassir, Z., Lithgow, T., Jenney, A., Cole, J. N., Nizet, V., Sorrell, T. C., Peleg, A.Y., Paterson, D. L., Beatson, S. A., Wu, J., Molloy, M. P., Syme, A. E., Goode, R. J. A., Hunter, A. A., Bowland, G., West, N. P., Wilkins, M. R., Djordjevic, S. P., Davies, M. R., Seemann, T., Howden, B. P., Pascovici, D., Tyagi, S., Schittenhelm, R. B., De Souza, D. P., McConville, M. J., Iredell, J. R., Cordwell, S. J., Strugnell, R. A., Stinear, T. P., Schembri, M. A. and Walker, M. J. 2023. Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria. Nature Communications. 14 (Art. 1530). https://doi.org/10.1038/s41467-023-37200-w
AuthorsMu, A., Klare, W. P., Baines, S. L., Ignatius Pang, C. N., Guérillot, R., Harbison-Price, N., Keller, N., Wilksch, J., Nhu, N. T. K., Phan, M-D., Keller, B., Nijagal, B., Tull, D., Dayalan, S., Chua, H. H. C., Skoneczny, D., Koval, J., Hachani, A., Shah, A. D., Neha, N., Jadhav, S., Partridge, S. R., Cork, A. J., Peters, K., Bertolla, O., Brouwer, S., Hancock, S. J., Álvarez-Fraga, L., De Oliveira, D. M. P., Forde, B., Dale, A., Mujchariyakul, W., Walsh, C. J., Monk, I., Fitzgerald, A., Lum, M., Correa-Ospina, C., Roy Chowdhury, P., Parton, R. G., De Voss, J., Beckett, J., Monty, F., McKinnon, J., Song, X., Stephen, J. R., Everest, M., Bellgard, M. I., Tinning, M., Leeming, M., Hocking, D., Jebeli, L., Wang, N., Ben Zakour, N., Yasar, S. A., Vecchiarelli, S., Russell, T., Zaw, T., Chen, T., Teng, D., Kassir, Z., Lithgow, T., Jenney, A., Cole, J. N., Nizet, V., Sorrell, T. C., Peleg, A.Y., Paterson, D. L., Beatson, S. A., Wu, J., Molloy, M. P., Syme, A. E., Goode, R. J. A., Hunter, A. A., Bowland, G., West, N. P., Wilkins, M. R., Djordjevic, S. P., Davies, M. R., Seemann, T., Howden, B. P., Pascovici, D., Tyagi, S., Schittenhelm, R. B., De Souza, D. P., McConville, M. J., Iredell, J. R., Cordwell, S. J., Strugnell, R. A., Stinear, T. P., Schembri, M. A. and Walker, M. J.
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.

JournalNature Communications
Journal citation14 (Art. 1530)
ISSN 2041-1723
Year2023
PublisherNature Research
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Digital Object Identifier (DOI)https://doi.org/10.1038/s41467-023-37200-w
Publication dates
Online18 Mar 2023
Publication process dates
Accepted06 Mar 2023
Deposited21 Apr 2023
FunderWellcome Trust
Bioplatforms Australia
National Health and Medical Research Council of Australia
Antibiotic Resistant Sepsis Pathogens Framework Initiative Consortium
National Collaborative Research Infrastructure Strategy
New South Wales State Government RAAP Scheme
Australian Cancer Research Foundation
Copyright holder© 2023, The Authors
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