Investigating the impact of phosphate acquisition and homeostasis on staphylococcus aureus pathogenesis

Kelliher, Jessica L.

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https://hdl.handle.net/2142/105129 Copy

Description

Title

Investigating the impact of phosphate acquisition and homeostasis on staphylococcus aureus pathogenesis

Author(s)

Kelliher, Jessica L.

Issue Date

2019-01-31

Director of Research (if dissertation) or Advisor (if thesis)

Kehl-Fie, Thomas E.

Doctoral Committee Chair(s)

Kehl-Fie, Thomas E.

Committee Member(s)

• Metcalf, William W.
• Slauch, James M.
• Wilson, Brenda A.

Department of Study

Microbiology

Discipline

Microbiology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Staphylococcus aureus, phosphate, transporter, pathogenesis

Abstract

Phosphate is an essential nutrient for all organisms. Therefore, transporters and regulatory systems in bacterial pathogens enabling phosphate acquisition within the host are important for virulence. However, the contribution of phosphate homeostasis to infection by the ubiquitous pathogen Staphylococcus aureus has not been evaluated. Bioinformatic analysis revealed that S. aureus encodes three inorganic phosphate (Pi) transporters: PstSCAB, PitA, and NptA. Each transporter imports Pi optimally in distinct environments. Interestingly, although loss of PstSCAB results in decreased virulence of several well-studied pathogens, a ΔpstSCAB mutant of S. aureus was not attenuated. However, these studies establish an important role for NptA in the pathogenesis of S. aureus. Although NptA has been sparsely characterized in bacteria, NptA homologs are widespread, suggesting that this type of Pi transporter may broadly contribute to pathogenesis. To regulate phosphate acquisition and homeostasis, bacteria contain a conserved, Pi-responsive two-component system named PhoPR in Gram-positives. In the model organism Escherichia coli and many others, the PhoPR homologs interact with PstSCAB and an accessory protein named PhoU to sense Pi, and mutation of PstSCAB or PhoU results in constitutive PhoPR activation. In contrast, deleting pstSCAB or phoU does not lead to dysregulated PhoPR activation in S. aureus, indicating that Pi sensing in this organism is fundamentally different from the current paradigm established in E. coli. In S. aureus, PhoPR is required for staphylococcal growth during Pi starvation and for virulence. Interestingly, the subset of PhoPR-regulated genes that promotes infection varies depending on other environmental factors. This is exemplified by the observation that in the liver, PhoPR is necessary for expression of Pi transporters PstSCAB and NptA, while PhoPR-regulated factors other than Pi transporters are required for infection of the heart. Cumulatively, the findings herein establish an essential role for Pi acquisition and homeostasis in staphylococcal pathogenesis and suggest that these processes are markedly different in S. aureus than in established models.

Graduation Semester

2019-05

Type of Resource

text

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http://hdl.handle.net/2142/105129

Copyright and License Information

Copyright 2019 Jessica Kelliher

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