PXD029457

PXD029457 is an original dataset announced via ProteomeXchange.

Title	Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase
Description	The transition from growth to stationary phase is a natural response of bacteria to starvation and stress. When stress is alleviated and more favorable growth conditions return, bacteria resume proliferation without a significant loss in fitness. Although specific adaptations that enhance the persistence and survival of bacteria in stationary phase have been identified, mechanisms that help maintain the competitive fitness potential of non-dividing bacterial populations have remained obscure. Here, we demonstrate that staphylococci that enter stationary phase following growth in media supplemented with excess glucose undergo regulated cell death to maintain the competitive fitness potential of the population. Upon a decrease in extracellular pH, the acetate generated as a byproduct of glucose metabolism induces cytoplasmic acidification and extensive protein damage in non-dividing cells. Although cell death ensues,it does not occur as a passive consequence of protein damage. Instead, we demonstrate that the expression and activity of the ClpXP protease is induced, resulting in the degeneration of cellular antioxidant capacity and, ultimately,cell death. Under these conditions, inactivation of either clpX or clpP resulted in the extended survival of unfit cells in stationary phase, but at the cost of maintaining population fitness. Finally, we show that cell death from antibiotics that interfere with bacterial protein synthesis can also be partly ascribed to the corresponding increase in clpP expression and activity. The functional conservation of ClpP in eukaryotes and bacteria suggests that ClpP-dependent cell death and fitness maintenance may be a widespread phenomenon in these domains of life.
HostingRepository	PRIDE
AnnounceDate	2022-05-19
AnnouncementXML	Submission_2022-05-19_15:43:34.775.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029457
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vikas Kumar
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-01 04:59:37	ID requested
⏵ 1	2022-05-19 15:43:35	announced

Alqarzaee AA, Chaudhari SS, Islam MM, Kumar V, Zimmerman MC, Saha R, Bayles KW, Frees D, Thomas VC, Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase. Proc Natl Acad Sci U S A, 118(47):(2021) [pubmed]

submitter keyword: Staphylococcus aureus, clpP, clpX, sodA, cell death, stationary phase, competitive fitness

Vinai C Thomas
contact affiliation	Center for Staphylococcal Research Department of Pathology and Microbiology University of Nebraska Medical Center
contact email	vinai.thomas@unmc.edu
lab head
Vikas Kumar
contact affiliation	UNMC
contact email	vikas.kumar@unmc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029457
     1. Label: PRIDE project
     2. Name: Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase