This is a collaboration with Thomas Kehl-Fie and a student in his lab, Caroline Vermilya. The goal of this project is to identify homologs of two proteins central to the regulation of phosphate homeostasis in the opportunistic bacterial pathogen S. aureus. The two proteins' names are PhoU and PitR. More descriptions of the two proteins and their functional roles can be found in the notes in the docs folder (under development).
The query sequences used to initiate the analysis can be found in the data folder. Analyses, scripts and output files are stored in their respective folders.
Below are the title, authors and abstract for the manuscription in prepration.
Multiple clades of regulators contribute to bacterial phosphate homeostasis and pathogenesis
Caroline Vermilya, Eliot S. Joya Sandoval1, Jana N. Radin1, Gary J. Olsen, & Thomas E. Kehl-Fie1
Phosphate is both essential for life and toxic, necessitating that organisms tightly regulate phosphate acquisition. The molecular details of bacterial phosphate homeostasis have primarily been investigated using Escherichia coli, which possesses a single accessory regulator PhoU. This protein, in conjunction with an ABC-type phosphate importer, suppresses the phosphate starvation response and is essential for viability. The current investigation revealed that bacteria frequently possess multiple PhoU paralogs. Distributed in three clades each paralog associates with a specific phosphate importer family, PhoU and the Pst ABC transporter family, PitR and the Pit inorganic phosphate transporter family, and a PhoU-domain fused to a NptA sodium phosphate transporter. The antibiotic-resistant pathogen Staphylococcus aureus has a remarkable ability to obtain phosphate from divergent environments, which contributes to its ability to cause infection and possesses paralog-transporter pairs from all three clades. Investigation with S. aureus revealed that all three paralogs can regulate phosphate homeostasis but do so only with their cognate transporter. While all three paralogs can regulate phosphate homeostasis, there is hierarchy. In standard culture conditions PitR is dominant to PhoU and the PhoU-domain of NptA. However, the hierarchy is modulated by the environment leading both PitR and PhoU to independently contribute to S. aureus virulence during systemic infection. Cumulatively, these investigations reveal that microbes possess multiple distinct groups of accessory regulatory proteins and that this previously unrealized diversity enables microbes to control phosphate homeostasis in diverse environments, including those encountered by pathogens during infection.