PhoPR contributes to staphylococcus aureus Growth during phosphate starvation and pathogenesis in an environment- specific manner

Jessica L. Kelliher, Jana N. Radin, Thomas E. Kehl-Fie

Research output: Contribution to journalArticle

Abstract

Microbial pathogens must obtain all essential nutrients, including phosphate, from the host. To optimize phosphate acquisition in diverse and dynamic environments, such as mammalian tissues, many bacteria use the PhoPR two-component system. Despite the necessity of this system for virulence in several species, PhoPR has not been studied in the major human pathogen Staphylococcus aureus. To illuminate its role in staphylococcal physiology, we initially assessed whether PhoPR controls the expression of the three inorganic phosphate (P i ) importers (PstSCAB, NptA, and PitA) in S. aureus. This analysis revealed that PhoPR is required for the expression of pstSCAB and nptA and can modulate pitA expression. Consistent with a role in phosphate homeostasis, PhoPR-mediated regulation of the transporters is influenced by phosphate availability. Further investigations revealed that PhoPR is necessary for growth under P i -limiting conditions, and in some environments, its primary role is to induce the expression of pstSCAB or nptA. Interestingly, in other environments, PhoPR is necessary for growth independent of P i transporter expression, indicating that additional PhoPR-regulated factors promote S. aureus adaptation to low-P i conditions. Together, these data suggest that PhoPR differentially contributes to growth in an environment-specific manner. In a systemic infection model, a mutant of S. aureus lacking PhoPR is highly attenuated. Further investigation revealed that PhoPRregulated factors, in addition to P i transporters, are critical for staphylococcal pathogenesis. Cumulatively, these findings point to an important role for PhoPR in orchestrating P i acquisition as well as transporter-independent mechanisms that contribute to S. aureus virulence.

Original languageEnglish (US)
Article numbere00371-18
JournalInfection and immunity
Volume86
Issue number10
DOIs
StatePublished - Oct 1 2018

Keywords

  • Infection
  • Infectious disease
  • NptA
  • PhoPR
  • Phosphate homeostasis
  • PstSCAB
  • Staphylococcus aureus
  • Two-component system

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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