Abstract
In iron-replete environments, the Pseudomonas aeruginosa Fur (ferric uptake regulator) protein represses expression of two small regulatory RNAs encoded by prrF1 and prrF2. Here we describe the effects of iron and PrrF regulation on P. aeruginosa physiology. We show that PrrF represses genes encoding enzymes for the degradation of anthranilate (i.e. antABC), a precursor of the Pseudomonas quinolone signal (PQS). Under iron-limiting conditions, PQS production was greatly decreased in a DeltaprrF1,2 mutant as compared with wild type. The addition of anthranilate to the growth medium restored PQS production to the DeltaprrF1,2 mutant, indicating that its defect in PQS production is a consequence of anthranilate degradation. PA2511 was shown to encode an anthranilate-dependent activator of the ant genes and was subsequently renamed antR. AntR was not required for regulation of antA by PrrF but was required for optimal iron activation of antA. Furthermore, iron was capable of activating both antA and antR in a DeltaprrF1,2 mutant, indicating the presence of two distinct yet overlapping pathways for iron activation of antA (AntR-dependent and PrrF-dependent). Additionally, several quorum-sensing regulators, including PqsR, influenced antA expression, demonstrating that regulation of anthranilate metabolism is intimately woven into the quorum-sensing network of P. aeruginosa. Overall, our data illustrate the extensive control that both iron regulation and quorum sensing exercise in basic cellular physiology, underlining how intermediary metabolism can affect the regulation of virulence factors in P. aeruginosa.
Highlights
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in immuno-compromised individuals, such as burn victims, and in cystic fibrosis (CF)2
The data presented in this study demonstrate the extensive control that iron exerts on P. aeruginosa physiology via the PrrF small regulatory RNAs, the roles of which extend beyond iron homeostasis and into control over metabolism and virulence
The extent of PrrF regulation is demonstrated by the marked effect that prrF1,2 deletion has on expression of the genes for anthranilate degradation and the result of this regulation with regard to Pseudomonas quinolone signal (PQS) production
Summary
In iron-replete environments, the Pseudomonas aeruginosa Fur (ferric uptake regulator) protein represses expression of two small regulatory RNAs encoded by prrF1 and prrF2. We describe the effects of iron and PrrF regulation on P. aeruginosa physiology. We show that PrrF represses genes encoding enzymes for the degradation of anthranilate (i.e. antABC), a precursor of the Pseudomonas quinolone signal (PQS). AntR was not required for regulation of antA by PrrF but was required for optimal iron activation of antA. Our data illustrate the extensive control that both iron regulation and quorum sensing exercise in basic cellular physiology, underlining how intermediary metabolism can affect the regulation of virulence factors in P. aeruginosa. PQS, acting as a coinducer for the LysR-type regulator PqsR (MvfR), activates the transcription of several virulence factors and the pqsABCDE operon, the gene products of which direct the synthesis of PQS (18 –20). PQS synthesis involves the condensation of a fatty acid with anthranilate, a metabolite that can alternatively be converted by sevdialyzed TSB; MOPS, 4-morpholinepropanesulfonic acid; IPTG, isopropyl-1-thio--D-galactopyranoside; HSL, homoserine lactone; RT-PCR, reverse transcription-PCR
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