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Heat-shock proteases promote survival of Pseudomonas aeruginosa during growth arrest

Basta, David W. and Angeles-Albores, David and Spero, Melanie A. and Ciemniecki, John A. and Newman, Dianne K. (2020) Heat-shock proteases promote survival of Pseudomonas aeruginosa during growth arrest. Proceedings of the National Academy of Sciences of the United States of America, 117 (8). pp. 4358-4367. ISSN 0027-8424. PMCID PMC7049150. https://resolver.caltech.edu/CaltechAUTHORS:20200206-163326208

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Abstract

When nutrients in their environment are exhausted, bacterial cells become arrested for growth. During these periods, a primary challenge is maintaining cellular integrity with a reduced capacity for renewal or repair. Here, we show that the heat-shock protease FtsH is generally required for growth arrest survival of Pseudomonas aeruginosa, and that this requirement is independent of a role in regulating lipopolysaccharide synthesis, as has been suggested for Escherichia coli. We find that ftsH interacts with diverse genes during growth and overlaps functionally with the other heat-shock protease-encoding genes hslVU, lon, and clpXP to promote survival during growth arrest. Systematic deletion of the heat-shock protease-encoding genes reveals that the proteases function hierarchically during growth arrest, with FtsH and ClpXP having primary, nonredundant roles, and HslVU and Lon deploying a secondary response to aging stress. This hierarchy is partially conserved during growth at high temperature and alkaline pH, suggesting that heat, pH, and growth arrest effectively impose a similar type of proteostatic stress at the cellular level. In support of this inference, heat and growth arrest act synergistically to kill cells, and protein aggregation appears to occur more rapidly in protease mutants during growth arrest and correlates with the onset of cell death. Our findings suggest that protein aggregation is a major driver of aging and cell death during growth arrest, and that coordinated activity of the heat-shock response is required to ensure ongoing protein quality control in the absence of growth.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.1912082117DOIArticle
https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1912082117/-/DCSupplementalPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7049150/PubMed CentralArticle
https://doi.org/10.7907/K6X1-GS91Related ItemCaltech PhD thesis (DWB)
ORCID:
AuthorORCID
Basta, David W.0000-0003-4176-6566
Angeles-Albores, David0000-0001-5497-8264
Spero, Melanie A.0000-0003-3291-2138
Newman, Dianne K.0000-0003-1647-1918
Additional Information:© 2020 The Author(s). Published under the PNAS license. Edited by Caroline S. Harwood, University of Washington, Seattle, WA, and approved January 8, 2020 (received for review July 14, 2019) PNAS first published February 6, 2020. We thank members of the D.K.N. laboratory for thoughtful discussions and critical feedback on the manuscript, and Lisa Racki (The Scripps Research Institute) for the gift of pLREX97. This manuscript derives from a chapter in D.W.B.’s doctoral thesis from the California Institute of Technology. This work was supported by the Millard and Muriel Jacobs Genetics and Genomics Laboratory at the California Institute of Technology and by the NIH (1R01AI127850-01A1 and 1R21AI146987-01). Author contributions: D.W.B., D.A.-A., M.A.S., J.A.C., and D.K.N. designed research; D.W.B., D.A.-A., M.A.S., and J.A.C. performed research; D.W.B., D.A.-A., M.A.S., J.A.C., and D.K.N. analyzed data; and D.W.B. and D.K.N. wrote the paper. The authors declare no competing interest. This article is a PNAS Direct Submission. This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1912082117/-/DCSupplemental.
Group:Millard and Muriel Jacobs Genetics and Genomics Laboratory
Funders:
Funding AgencyGrant Number
Millard and Muriel Jacobs Genetics and Genomics LaboratoryUNSPECIFIED
NIH1R01AI127850-01A1
NIH1R21AI146987-01
Subject Keywords:Pseudomonas aeruginosa | growth arrest | survival | proteostasis | FtsH
Issue or Number:8
PubMed Central ID:PMC7049150
Record Number:CaltechAUTHORS:20200206-163326208
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200206-163326208
Official Citation:Heat-shock proteases promote survival of Pseudomonas aeruginosa during growth arrest. David W. Basta, David Angeles-Albores, Melanie A. Spero, John A. Ciemniecki, Dianne K. Newman. Proceedings of the National Academy of Sciences Feb 2020, 117 (8) 4358-4367; DOI: 10.1073/pnas.1912082117
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101176
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:07 Feb 2020 19:16
Last Modified:10 Apr 2020 22:26

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