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Multiple clades of regulators contribute to bacterial phosphate homeostasis and pathogenesis
Preprint   Open access

Multiple clades of regulators contribute to bacterial phosphate homeostasis and pathogenesis

Caroline Vermilya, Eliot S Joya Sandoval, Jana N Radin, Gary J Olsen, Bin Z He and Thomas E Kehl-Fie
bioRxiv
Cold Spring Harbor Laboratory
09/08/2025
DOI: 10.1101/2025.09.08.674922
PMCID: PMC12439885
PMID: 40964295
url
https://doi.org/10.1101/2025.09.08.674922View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Phosphate is both essential for life and toxic, necessitating the tight regulation of its acquisition. Based on , most bacteria are thought to use a single accessory protein that monitors import to regulate phosphate homeostasis. This work reveals that most bacteria possess multiple distinct families of accessory regulators with each family regulating homeostasis in conjunction with a unique importer family. The antibiotic-resistant pathogen can obtain phosphate from divergent environments and possesses accessory-transporter pairs from all three identified groups. Investigations with revealed that all three accessory proteins can regulate phosphate homeostasis, but that there is a hierarchy, which is dictated by the environment. Multiple accessory regulators are independently necessary for to cause infection. Thus, microbes possess not one, but multiple distinct groups of accessory regulatory proteins and this diversity enables them to control phosphate homeostasis across environments, including those encountered during infection.

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