As the increase in rap transcription in a pstS mutant is below 2-fold,
we believe that a 35% reduction in activation, in response to Pi limitation, may be undetectable. An alternative explanation could be that rap is induced via PhoBR, but not in response to Pi limitation. Previously, PhoBR has been shown to activate expression of the asr (acid shock RNA) gene, but Pi limitation did not activate asr expression . In addition, there is also evidence that PhoB can be activated by non-partner histidine kinases, in the absence of PhoR . This has lead to the hypothesis that PhoBR may activate genes in response to a variety of environmental cues, in addition to Pi limitation . It may not be learn more entirely accurate to describe the effect of a pstS mutation, or Pi limitation, on QS as ‘upregulation’. For QS to function correctly, it is the absolute concentrations of the AHL signal molecule that is critical, not the amount per cell . Due to the growth defect observed following a pstS mutation or Pi limitation, the amount of AHL
per cell is increased, but the absolute value remains comparable to WT/Pi excess conditions. Therefore, Selonsertib it may be more accurate to state that the upregulation of smaI transcription, following pstS mutation or Pi limitation, allows maintenance of QS regulon control despite the reduced growth rate. This idea is supported by the fact that although carR, pigQ, pigR and rap are all regulated by QS in Serratia 39006 [28, 29], only rap transcription is upregulated in response to a pstS mutation. Our experiments indicate that, in response to a pst mutation, rap is activated
independently of QS, and that activation may be mediated via PhoB. Activation of carA expression, following pstS mutation, was previously reported to be dependent on the upregulation of QS . However, as Rap is also an activator of carA transcription , it is possible that Rap, rather than QS, is responsible for the activation of carA following a pstS mutation. We propose that a dual mechanism, involving (1) the alleviation of SmaR repression at lower cell density, Tryptophan synthase via upregulation of smaI, and (2) increased levels of Rap via PhoB mediated transcriptional activation, is responsible for the increase in carA expression following pstS mutation. In the absence of AHL (and hence constitutive SmaR repression), carA transcription is essentially abolished  and hence, further activation by Rap, in response to a pstS mutation, might not be possible. Based on our data, we propose a model by which Pi limitation results in upregulation of secondary metabolism via multiple inter-linked pathways (Fig. 9). In response to Pi limitation, or following mutation of the pstSCAB genes, PhoB is activated by phosphorylation [9, 15, 16]. PhoB~P can then activate expression of genes involved in the Serratia phosphate response which includes smaI, pigA and rap. Activation of pigA expression causes increased Pig Survivin inhibitor production.