Abstract
Pseudomonas aeruginosa is a Gram-negative bacterium which can cause serious infections among immune-depressed people including cystic fibrosis patients where it can colonize the lungs causing chronic infections. Iron is essential for P. aeruginosa and can be provided via three sources under aerobic conditions: its own siderophores pyochelin (PCH) and pyoverdine (PVD), xenosiderophores, or heme, respectively. Pyoverdine is the high affinity siderophore and its synthesis and uptake involve more than 30 genes organized in different operons. Its synthesis and uptake are triggered by iron scarcity via the Fur regulator and involves two extra cytoplasmic sigma factors (ECF), PvdS for the biosynthesis of PVD and FpvI for the uptake via the TonB-dependent FpvA outer membrane transporter and other periplasmic and inner membrane proteins. It appeared recently that the regulation of PVD biosynthesis and uptake involves other regulators, including other ECF factors, and LysR regulators. This is the case especially for the genes coding for periplasmic and inner membrane proteins involved in the reduction of Fe3+ to Fe2+ and the transport of ferrous iron to the cytoplasm that appears to represent a crucial step in the uptake process.
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References
Attila C, Ueda A, Wood TK (2008) PA2663 (PpyR) increases biofilm formation in Pseudomonas aeruginosa PAO1 through the psl operon and stimulates virulence and quorum-sensing phenotypes. Appl Microbiol Biotechnol 78(2):293–307. https://doi.org/10.1007/s00253-007-1308-y
Beare PA, For RJ, Martin LW, Lamont IL (2003) Siderophore-mediated cell signalling in Pseudomonas aeruginosa: divergent pathways regulate virulence factor production and siderophore receptor synthesis. Mol Microbiol 47(1):195–207. https://doi.org/10.1046/j.1365-2958.2003.03288.x
Blanka A, Schulz S, Eckweiler D, Franke R, Bielecka A, Nicolai T et al (2014) Identification of the alternative sigma factor SigX regulon and its implications for Pseudomonas aeruginosa pathogenicity. J Bacteriol 196(2):345–356. https://doi.org/10.1128/JB.01034-13
Boechat AL, Kaihami GH, Politi MJ, Lepine F, Baldini RL (2013) A novel role for an ECF sigma factor in fatty acid biosynthesis and membrane fluidity in Pseudomonas aeruginosa. PLoS ONE 8(12):e84775. https://doi.org/10.1371/journal.pone.0084775
Bonneau A, Roche B, Schalk IJ (2020) Iron acquisition in Pseudomonas aeruginosa by the siderophore pyoverdine: an intricate interacting network including periplasmic and membrane proteins. Sci Rep 10(1):120. https://doi.org/10.1038/s41598-019-56913-x
Bouffartigues E, Si Hadj Mohand I, Maillot O, Tortuel D, Omnes J, David A et al (2020) The temperature-regulation of Pseudomonas aeruginosa cmaX-cfrX-cmpX operon reveals an intriguing molecular network involving the sigma factors AlgU and SigX. Front Microbiol 11:579495. https://doi.org/10.3389/fmicb.2020.579495
Brillet K, Ruffenach F, Adams H, Journet L, Gasser V, Hoegy F et al (2012) An ABC transporter with two periplasmic binding proteins involved in iron acquisition in Pseudomonas aeruginosa. ACS Chem Biol 7(12):2036–2045. https://doi.org/10.1021/cb300330v
Cai Z, Yang F, Shao X, Yue Z, Li Z, Song Y et al (2022) ECF sigma factor HxuI is critical for in vivo fitness of Pseudomonas aeruginosa during infection. Microbiol Spectr. https://doi.org/10.1128/spectrum.01620-21
Chevalier S, Bouffartigues E, Bazire A, Tahrioui A, Duchesne R, Tortuel D et al (2019) Extracytoplasmic function sigma factors in Pseudomonas aeruginosa. Biochim Biophys Acta Gene Regul Mech 1862(7):706–721. https://doi.org/10.1016/j.bbagrm.2018.04.008
Cornelis P, Dingemans J (2013) Pseudomonas aeruginosa adapts its iron uptake strategies in function of the type of infections. Front Cell Infect Microbiol 3:75. https://doi.org/10.3389/fcimb.2013.00075
Escolar L, Perez-Martin J, de Lorenzo V (1999) Opening the iron box: transcriptional metalloregulation by the Fur protein. J Bacteriol 181(20):6223–6229. doi: https://doi.org/10.1128/JB.181.20.6223-6229.1999
Flechard M, Duchesne R, Tahrioui A, Bouffartigues E, Depayras S, Hardouin J et al (2018) The absence of SigX results in impaired carbon metabolism and membrane fluidity in Pseudomonas aeruginosa. Sci Rep 8(1):17212. https://doi.org/10.1038/s41598-018-35503-3
Frangipani E, Visaggio D, Heeb S, Kaever V, Camara M, Visca P et al (2014) The Gac/Rsm and cyclic-di-GMP signalling networks coordinately regulate iron uptake in Pseudomonas aeruginosa. Environ Microbiol 16(3):676–688. https://doi.org/10.1111/1462-2920.12164
Ganne G, Brillet K, Basta B, Roche B, Hoegy F, Gasser V et al (2017) Iron release from the siderophore pyoverdine in Pseudomonas aeruginosa involves three new actors: FpvC, FpvG, and FpvH. ACS Chem Biol 12(4):1056–1065. https://doi.org/10.1021/acschembio.6b01077
Ge L, Seah SY (2006) Heterologous expression, purification, and characterization of an l-ornithine N(5)-hydroxylase involved in pyoverdine siderophore biosynthesis in Pseudomonas aeruginosa. J Bacteriol 188(20):7205–7210. https://doi.org/10.1128/JB.00949-06
Ghysels B, Ochsner U, Mollman U, Heinisch L, Vasil M, Cornelis P et al (2005) The Pseudomonas aeruginosa pirA gene encodes a second receptor for ferrienterobactin and synthetic catecholate analogues. FEMS Microbiol Lett 246(2):167–174. https://doi.org/10.1016/j.femsle.2005.04.010
Imperi F, Putignani L, Tiburzi F, Ambrosi C, Cipollone R, Ascenzi P et al (2008) Membrane-association determinants of the omega-amino acid monooxygenase PvdA, a pyoverdine biosynthetic enzyme from Pseudomonas aeruginosa. Microbiol (Reading) 154(Pt 9):2804–2813. https://doi.org/10.1099/mic.0.2008/018804-0
Imperi F, Tiburzi F, Fimia GM, Visca P (2010) Transcriptional control of the pvdS iron starvation sigma factor gene by the master regulator of sulfur metabolism CysB in Pseudomonas aeruginosa. Environ Microbiol 12(6):1630–1642. https://doi.org/10.1111/j.1462-2920.2010.02210.x
Kong W, Zhao J, Kang H, Zhu M, Zhou T, Deng X et al (2015) ChIP-seq reveals the global regulator AlgR mediating cyclic di-GMP synthesis in Pseudomonas aeruginosa. Nucleic Acids Res 43(17):8268–8282. https://doi.org/10.1093/nar/gkv747
Little AS, Okkotsu Y, Reinhart AA, Damron FH, Barbier M, Barrett B et al (2018) Pseudomonas aeruginosa AlgR phosphorylation status differentially regulates pyocyanin and pyoverdine production. MBio. https://doi.org/10.1128/mBio.02318-17
Llamas MA, Mooij MJ, Sparrius M, Vandenbroucke-Grauls CM, Ratledge C, Bitter W (2008) Characterization of five novel Pseudomonas aeruginosa cell-surface signalling systems. Mol Microbiol 67(2):458–472. https://doi.org/10.1111/j.1365-2958.2007.06061.x
Llamas MA, Imperi F, Visca P, Lamont IL (2014) Cell-surface signaling in Pseudomonas: stress responses, iron transport, and pathogenicity. FEMS Microbiol Rev 38(4):569–597. doi: https://doi.org/10.1111/1574-6976.12078
Lyczak JB, Cannon CL, Pier GB (2000) Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2(9):1051–1060. https://doi.org/10.1016/s1286-4579(00)01259-4
Meyer JM, Neely A, Stintzi A, Georges C, Holder IA (1996) Pyoverdin is essential for virulence of Pseudomonas aeruginosa. Infect Immun 64(2):518–523. https://doi.org/10.1128/iai.64.2.518-523.1996
Mossialos D, Ochsner U, Baysse C, Chablain P, Pirnay JP, Koedam N et al (2002) Identification of new, conserved, non-ribosomal peptide synthetases from fluorescent pseudomonads involved in the biosynthesis of the siderophore pyoverdine. Mol Microbiol 45(6):1673–1685. doi: https://doi.org/10.1046/j.1365-2958.2002.03120.x
Ochsner UA, Vasil AI, Vasil ML (1995) Role of the ferric uptake regulator of Pseudomonas aeruginosa in the regulation of siderophores and exotoxin A expression: purification and activity on iron-regulated promoters. J Bacteriol 177(24):7194–7201. https://doi.org/10.1128/jb.177.24.7194-7201.1995
Ochsner UA, Vasil ML, Alsabbagh E, Parvatiyar K, Hassett DJ (2000) Role of the Pseudomonas aeruginosa oxyR-recG operon in oxidative stress defense and DNA repair: OxyR-dependent regulation of katB-ankB, ahpB, and ahpC-ahpF. J Bacteriol 182(16):4533–4544. https://doi.org/10.1128/JB.182.16.4533-4544.2000
Ochsner UA, Wilderman PJ, Vasil AI, Vasil ML (2002) GeneChip expression analysis of the iron starvation response in Pseudomonas aeruginosa: identification of novel pyoverdine biosynthesis genes. Mol Microbiol 45(5):1277–1287. https://doi.org/10.1046/j.1365-2958.2002.03084.x
Pletzer D, Braun Y, Weingart H (2016) Swarming motility is modulated by expression of the putative xenosiderophore transporter SppR-SppABCD in Pseudomonas aeruginosa PA14. Antonie Van Leeuwenhoek 109(6):737–753. https://doi.org/10.1007/s10482-016-0675-8
Ravel J, Cornelis P (2003) Genomics of pyoverdine-mediated iron uptake in pseudomonads. Trends Microbiol 11(5):195–200
Reen FJ, Haynes JM, Mooij MJ, O’Gara F (2013) A non-classical LysR-type transcriptional regulator PA2206 is required for an effective oxidative stress response in Pseudomonas aeruginosa. PLoS ONE 8(1):e54479. https://doi.org/10.1371/journal.pone.0054479
Schulz S, Eckweiler D, Bielecka A, Nicolai T, Franke R, Dotsch A et al (2015) Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals a modular architecture with limited and function-specific crosstalk. PLoS Pathog 11(3):e1004744. https://doi.org/10.1371/journal.ppat.1004744
Trouillon J, Imbert L, Villard AM, Vernet T, Attree I, Elsen S (2021) Determination of the two-component systems regulatory network reveals core and accessory regulations across Pseudomonas aeruginosa lineages. Nucleic Acids Res. https://doi.org/10.1093/nar/gkab928
Vinckx T, Matthijs S, Cornelis P (2008) Loss of the oxidative stress regulator OxyR in Pseudomonas aeruginosa PAO1 impairs growth under iron-limited conditions. FEMS Microbiol Lett 288(2):258–265. https://doi.org/10.1111/j.1574-6968.2008.01360.x
Visca P, Imperi F, Lamont IL (2007) Pyoverdine siderophores: from biogenesis to biosignificance. Trends Microbiol 15(1):22–30. doi: https://doi.org/10.1016/j.tim.2006.11.004
Wei Q, Minh PN, Dotsch A, Hildebrand F, Panmanee W, Elfarash A et al (2012) Global regulation of gene expression by OxyR in an important human opportunistic pathogen. Nucleic Acids Res 40(10):4320–4333. doi: https://doi.org/10.1093/nar/gks017
Wilderman PJ, Vasil AI, Johnson Z, Wilson MJ, Cunliffe HE, Lamont IL et al (2001) Characterization of an endoprotease (PrpL) encoded by a PvdS-regulated gene in Pseudomonas aeruginosa. Infect Immun 69(9):5385–5394. https://doi.org/10.1128/IAI.69.9.5385-5394.2001
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Cornelis, P., Tahrioui, A., Lesouhaitier, O. et al. High affinity iron uptake by pyoverdine in Pseudomonas aeruginosa involves multiple regulators besides Fur, PvdS, and FpvI. Biometals 36, 255–261 (2023). https://doi.org/10.1007/s10534-022-00369-6
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DOI: https://doi.org/10.1007/s10534-022-00369-6