Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria
Article
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
Authors | 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. |
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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. |
Journal | Nature Communications |
Journal citation | 14 (Art. 1530) |
ISSN | 2041-1723 |
Year | 2023 |
Publisher | Nature Research |
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Digital Object Identifier (DOI) | https://doi.org/10.1038/s41467-023-37200-w |
Publication dates | |
Online | 18 Mar 2023 |
Publication process dates | |
Accepted | 06 Mar 2023 |
Deposited | 21 Apr 2023 |
Funder | Wellcome 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 |
https://repository.uel.ac.uk/item/8vy1v
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