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Playing the Long Game: A Phosphatase Promotes <em>Escherichia coli</em> Survival in Long-Term Stationary Phase Akash Sinha

Dissertations & Theses @ University of Pennsylvania Available online

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Format:
Book
Thesis/Dissertation
Author/Creator:
Sinha, Akash, author.
Contributor:
University of Pennsylvania. Biology., degree granting institution.
Language:
English
Subjects (All):
0306.
0369.
0379.
0410.
Local Subjects:
0306.
0369.
0379.
0410.
Physical Description:
1 electronic resource (97 pages)
Contained In:
Dissertations Abstracts International 87-07B
Place of Publication:
Ann Arbor : ProQuest Dissertations and Theses, 2025
Language Note:
English
Summary:
Bacteria inhabit diverse natural environments, many of which are nutrient-poor. Despite nutrient limitation, they maintain their viability by entering a quiescent state and resuming growth when favorable conditions return. In laboratory cultures, this phenomenon is observed during stationary phase, where cell division and metabolism are slowed down. The various factors responsible for maintaining stationary phase viability are actively being studied. Here, we identify one such factor, SixA, to be responsible for maintaining Long-term stationary phase survival of Escherichia coli. SixA is a phosphohistidine phosphatase conserved across bacterial species but with only few known substrates. We show that the loss of sixA drastically reduces E. coli survival during long-term stationary phase by disrupting nucleotide homeostasis and elevating cellular ATP levels. This physiological fitness defect results from the loss of SixA-mediated dephosphorylation of nucleoside diphosphate kinase (Ndk), which catalyzes the conversion of nucleoside diphosphates to triphosphates. Our identification of Ndk as a SixA substrate reveals a method for post-translational control of Ndk in prokaryotes. We also show that sixA expression increases during stationary phase through the accumulated stringent response alarmone ppGpp. Additionally, SixA is upregulated by envelope stress response factors, indicating multimodal regulation that integrates starvation and envelope stress. The regulation of SixA and its critical role in stationary phase survival not only establishes a new function for phosphohistidine phosphatases in bacteria but also advances our understanding of bacterial physiology during stationary phase
Notes:
Advisors: Goulian, Mark Committee members: Daldal, Fevzi; Pohlschröder, Mecky; Zhu, Jun Jay; Zackular, Joseph P.
Source: Dissertations Abstracts International, Volume: 87-07, Section: B.
Ph.D. University of Pennsylvania 2025
Vendor supplied data
Local Notes:
School code: 0175
ISBN:
9798276001289
Access Restriction:
Restricted for use by site license

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