Pi Sensing by P aeruginosa and Its Interaction with the QS System A Conserved Mechanism of Virulence Activation in Nosocomial Pathogens

Pi concentration [Pi] appears to be not only important to the activation of P. aerugi-nosa to express a lethal phenotype, but also to multiple pathogens relevant to gut-derived sepsis following surgical injury and stress. From the standpoint of the microbe, [Pi] could be viewed as a marker of relative energy abundance in eukaryotic cells and hence a surrogate marker for tissue homeostasis versus dysfunction. On this level, it seems logical that bacteria have evolved sophisticated sensory systems to detect [Pi]. A highly conserved two-component phosphor-sensor system consisting of an inner membrane histidine kinase PhoR and transcriptional regulator PhoB is present in various bacteria associated with gut-derived sepsis. This system controls the expression of the PhoB regulated genes via binding of PhoB to its specific DNA binding site pho. The pho box has been identified upstream of multiple genes including those of the QS regulon. As such Pi depletion can induce the expression of virulence through its effect on quorum sensing (Fig. 9.1c) (Zaborin et al. 2009). Although there is considerable information on the regulation of microbial metabolism and virulence during low Pi conditions in vitro, there is virtually no information on how Pi concentration affects microbial lethality in vivo. As mentioned above, remarkably the concentration of Pi within tissue sites of microbial colonization during health or disease is essentially unstudied. It is assumed that the intestinal tract does not represent a site of low [Pi] as luminal Pi is predicted to be abundant from oral nutrition. However, as we have shown, mucus [Pi] may be of more importance to intestinal pathogens as they attach to mucus during colonization and invasion. Given the importance of local [Pi] to be sensed by such a wide variety of intestinal bacteria, more detailed study of the concentration of phosphate is needed to understand its relevance in infection-related mortality during severe host stress (Lamarche et al. 2008).

High [Pi] Represses PhoB by binding to PstS

Low [Pi] Activates Virulence

Pho box

MICROBE

MECHANISM

REFERENCE

Escherichia coli

Isaacson (2002)

Klebsiella pneumonia

(2005)

Proteus mirabilis

(2004)

Streptococcus pneumonia

PhoB

Polissi et al. (1998)

Acenitobacter sp

ppk

Darwin & Miller (1999)

Enterococcus

PhoB

Grant et al. (2005)

Low [Pi] Causes PhoB activation by up-regulation of PstS, release of PhoR and PhoB phosphorylation

Pi I

Quorum Sensing Activation Expression of Virulence Factors

Low [Pi] Causes PhoB activation by up-regulation of PstS, release of PhoR and PhoB phosphorylation

Pi I

Quorum Sensing Activation Expression of Virulence Factors

Fig. 9.1 The PstS-PhoB phosphate sensing system. (Panel A) High extracellular [Pi] binds PstS causing PhoR to remain bound to the multi-component mem brane complex. (Panel B) When PstS is activated by low [Pi], PhoR release leads to PhoB phosphorylation (PhoB-Pi), which then activates QS leading to vira lence expression. (Panel C) Various pathogens of clinical relevance activate their virulence in response to low [Pi] via PhoB (Van Dien and Keasling 1998)

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