Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress Article Swipe
Magdalena Podkowik
,
Andrew I. Perault
,
Gregory Putzel
,
Andrew W. Pountain
,
Jisun Kim
,
Ashley Dumont
,
Erin E. Zwack
,
Robert J. Ulrich
,
Theodora K. Karagounis
,
Chunyi Zhou
,
Andreas F. Haag
,
Julia Shenderovich
,
Gregory A. Wasserman
,
Junbeom Kwon
,
John Chen
,
Anthony R. Richardson
,
Jeffrey N. Weiser
,
Carla R. Nowosad
,
Desmond S. Lun
,
Dane Parker
,
Alejandro Pironti
,
Xilin Zhao
,
Karl Drlica
,
Itai Yanai
,
Victor J. Torres
,
Bo Shopsin
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.7554/elife.89098.2
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.7554/elife.89098.2
The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr increased both respiration and aerobic fermentation but decreased ATP levels and growth, suggesting that Δagr cells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived “memory” of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2−/−) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.7554/elife.89098.2
- https://github.com/elifesciences/enhanced-preprints-data/raw/master/data/89098/v2/89098-v2.pdf
- OA Status
- gold
- References
- 81
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4392368152
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4392368152Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.7554/elife.89098.2Digital Object Identifier
- Title
-
Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stressWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-03-04Full publication date if available
- Authors
-
Magdalena Podkowik, Andrew I. Perault, Gregory Putzel, Andrew W. Pountain, Jisun Kim, Ashley Dumont, Erin E. Zwack, Robert J. Ulrich, Theodora K. Karagounis, Chunyi Zhou, Andreas F. Haag, Julia Shenderovich, Gregory A. Wasserman, Junbeom Kwon, John Chen, Anthony R. Richardson, Jeffrey N. Weiser, Carla R. Nowosad, Desmond S. Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J. Torres, Bo ShopsinList of authors in order
- Landing page
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https://doi.org/10.7554/elife.89098.2Publisher landing page
- PDF URL
-
https://github.com/elifesciences/enhanced-preprints-data/raw/master/data/89098/v2/89098-v2.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://github.com/elifesciences/enhanced-preprints-data/raw/master/data/89098/v2/89098-v2.pdfDirect OA link when available
- Concepts
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Quorum sensing, Oxidative stress, Reactive oxygen species, Staphylococcus aureus, Biology, Virulence, Alternative oxidase, Microbiology, Oxidative phosphorylation, Wild type, Cell biology, Gene, Mutant, Mitochondrion, Biochemistry, Genetics, BacteriaTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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81Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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