Opportunistic use of catecholamine neurotransmitters as siderophores to access iron by Pseudomonas aeruginosa

Abstract

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Beta adrenergic receptor antagonist can modify Pseudomonas aeruginosa biofilm formation in vitro: Implications for chronic wounds

“…We find that the catecholamine neuromodulators and AR agonists, EPI and NE, promote both the planktonic growth and biofilm forming capacity of this organism, confirming earlier findings that showed norepinephrine increased virulence, motility and adhesion in strains of P. aeruginosa 23,42 . These studies pointed out the possible mechanism to include to chelation of iron by catecholamines for enhancing transport into P. aeruginosa cells possibly through the outer membrane receptor and transporter, TonB 60 . Significantly and newly reported here, the catecholamine growth‐enhancing effects can be reversed when the cultures are treated with the beta‐AR antagonist timolol (TIM).…”

“…This may be related to the receptors that transduce the catecholamine-mediated pyoverdine and pyocyanin responses. Although not fully identified, some potential catecholamine receptors for P. aeruginosa include the TonB Dependent Transporters PirA and PiuA 60 and the interconnected QS systems las, rhl and PQS. 23,71 Alternatively, secreted protein was sampled at 72 h, and longer incubation times may be needed to detect the change in translation of this protein.…”

How the Presence of Hemin Affects the Expression of the Different Iron Uptake Pathways in Pseudomonas aeruginosa Cells

“…Moreover, we have also shown that the presence of xenosiderophores in P. aeruginosa growth media often strongly induces the expression of the proteins of their corresponding uptake pathways. 26,32,35,36,41,45 Here, we first investigated the effect of 0.25 µM hemin on the expression of the TBDT genes hasR, phuR and hxuA, involved in hemin uptake in P. aeruginosa cells, using differential proteomic approaches. The intracellular concentration of hemin in eukaryotic cells is estimated to be between 0.025 and 0.3 µM, 55 and the KD of HasAp for hemin of 350 ± 50 nM, 6 leading us to choose the concentration of 0.25 µM hemin for our experiments.…”

“…35 As previously described, our differential proteomic data showed that the presence of 10 µM TCV alone in the medium of PAO1 induces the expression of pfeA (log2 fold change of 4.81), pfeE (log2 fold change of 5.55), and pirA, another TBDT also involved in iron uptake via catechol xenosiderophores, (log2 fold change of 2.05). 26,41,45,67,68 The presence of TCV also resulted in the repression of fptA expression (log2 fold change of -2.37) and that of many genes encoding proteins of the PCH-dependent iron-uptake pathway (Figure 7A). In the presence of both 10 µM TCV and 0.25 µM hemin, the expression of pfeA and pirA was still induced with the same efficiency as with TCV alone.…”

“…26 Previous proteomic and transcriptomic studies of our group have shown how P. aeruginosa adapts the expression of its various iron-uptake pathways to xenosiderophores. 26,35,41 Moreover, Hijazi et al showed that the absence of PVD and PCH biosynthesis increases the susceptibility of P. aeruginosa to Gallium-protoporphyrin (a toxic analogue of heme), suggesting an increase in hasR and phuR transcription 42 and a regulatory link between hemin acquisition systems via the HasR and PhuR proteins and PVD and PCH biosynthesis.…”