The distinct PhoPR mediated responses to phosphate limitation in Bacillus subtilis subspecies subtilis and spizizenii stem from differences in wall teichoic acid composition and metabolism

Abstract

The PhoPR-mediated response to phosphate limitation (PHO response) in Bacillus subtilis subsp subtilis is amplified and maintained by reducing the level of Lipid V composed of poly(glycerol phosphate), a wall teichoic acid (WTA) biosynthetic intermediate that inhibits PhoR autokinase activity. However, the reduction in Lipid V level is effected by activated PhoP∼P, raising the question of how the PHO response is first initiated. Furthermore, that WTA is composed of poly(ribitol phosphate) in Bacillus subtilis subsp spizizenii prompted an investigation of how the PHO response is regulated in that bacterium. We report that the PHO responses of B. subtilis subsp subtilis and subsp spizizenii are distinct. The PhoR kinases of the two B. subtilis subspecies are functionally equivalent and are activated either by the TagA/TarA or TagB/TarB enzyme product. However, they are inhibited by Lipid V composed of poly(glycerol phosphate) but not by Lipid V composed of poly(ribitol phosphate). Therefore, the distinctive PHO responses of these B. subtilis subspecies stem from the differential sensitivity of PhoR kinases to the polyol composition of Lipid V and from the genomic organization of WTA biosynthetic genes and the regulation of their expression.

Activation of the PhoPR-Mediated Response to Phosphate Limitation Is Regulated by Wall Teichoic Acid Metabolism in Bacillus subtilis

“…Since the PHO response is amplified in B. subtilis by two processes that require activated PhoP∼P (i.e., reduction of WTA synthesis and activation of teichuronic synthesis), it is evident that it must be initiated by a different PhoP∼P-independent mechanism. Thus, initiation of the PHO response was addressed in Bacillus subtilis subspecies spizizenii (hereafter called B. spizizenii ) that synthesizes WTA composed of poly(ribitol phosphate) ( tarABIJKL genes) ( Prunty et al, 2018 ). Investigation of the PHO response in B. spizizenii has the advantage that it is not amplified as in B. subtilis [i.e., WTA intermediates composed of poly(ribitol phosphate) do not inhibit PhoR autokinase activity], and expression of WTA biosynthetic enzymes is not repressed by PhoP∼P ( Prunty et al, 2018 ).…”

“…Thus, initiation of the PHO response was addressed in Bacillus subtilis subspecies spizizenii (hereafter called B. spizizenii ) that synthesizes WTA composed of poly(ribitol phosphate) ( tarABIJKL genes) ( Prunty et al, 2018 ). Investigation of the PHO response in B. spizizenii has the advantage that it is not amplified as in B. subtilis [i.e., WTA intermediates composed of poly(ribitol phosphate) do not inhibit PhoR autokinase activity], and expression of WTA biosynthetic enzymes is not repressed by PhoP∼P ( Prunty et al, 2018 ). Three pieces of evidence indicate that the PHO response is activated by an intermediate in WTA synthesis in B. spizizenii .…”

“…Three pieces of evidence indicate that the PHO response is activated by an intermediate in WTA synthesis in B. spizizenii . (1) In a strain with inducible expression of the tarABIJKL operon encoding the WTA biosynthetic enzymes, the magnitude of the PHO response is directly proportional to the level of added inducer ( Prunty et al, 2018 ). (2) The PHO response is increased in a strain of B. spizizenii unable to synthesize teichuronic acid, indicating that the onset of teichuronic acid synthesis reduces the level of a WTA intermediate that activates the PHO response ( Prunty et al, 2018 ).…”

“…The first mechanism, exemplified by PhoBR activation in E. coli , is responsive to phosphate transport and is mediated by the PstSCAB transporter and PhoU adaptor protein ( Hsieh and Wanner, 2010 ). The second mechanism, exemplified by PhoPR in B. subtilis , is responsive to WTA metabolism and is mediated by intermediates in WTA biosynthesis ( Botella et al, 2014 ; Prunty et al, 2018 ). Variation of both mechanisms is observed that enable bacteria to ensure an adequate phosphorous supply in their particular ecological niches.…”

The distinct PhoPR mediated responses to phosphate limitation in Bacillus subtilis subspecies subtilis and spizizenii stem from differences in wall teichoic acid composition and metabolism

“…In the article by Prunty et al . (), the authors want to add Eric Botella to the authorship of this paper. The authors are listed here correctly.…”