Targeted Killing of Pseudomonas aeruginosa by Pyocin G Occurs via the Hemin Transporter Hur

Atanaskovic, Iva; Mosbahi, Khédidja; Sharp, Connor; Housden, Nicholas G.; Kaminska, Renata; Walker, Daniel; Kleanthous, Colin

doi:10.1016/j.jmb.2020.04.020

Cited by 21 publications

(49 citation statements)

References 31 publications

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“…We repeated the same proteomic and qRT-PCR experiments with DFOB, and 13 observed similar induction of foxA transcription and expression ( Figures 2 and 3), as previously 14 shown. 22 The induction of transcription and expression of foxA was of the same intensity for 15 both exosiderophores. 16 In conclusion, foxA transcription and expression is induced by both NOCA and DFOB, showing 17 that these two siderophores use this TBDT to transport iron from the environment into the P. 18 aeruginosa periplasm.…”

Section: Introductionmentioning

confidence: 87%

“…P. aeruginosa can acquire iron 17 from the catechol exosiderophore enterobactin via the TBDTs PfeA and PirA , 17-20 and 18 vibriobactin via FvbA. 21 It can also use the exosiderophores mycobactin and 19 carboximycobactin via the TBDT FemA, 22 aerobactin, rhizobactin, and schizokinen by ChtA, 23 20 and citrate by FecA. 24 Hydroxamate siderophores are also used by P. aeruginosa, along with 21 ferrioxamine B (DFOB), transported by FoxA, 25,26 and ferrichrome (FRC), transported by 22 FiuA.…”

Section: Introductionmentioning

confidence: 99%

“…P. aeruginosa can sense the presence of iron-loaded exosiderophores in its 4 environment via AraC regulators, sigma factors, or two-component systems, resulting in the 5 induction of the transcription and expression of the corresponding TBDTs. 9,22,[29][30][31][32] We grew P. 6 aeruginosa PAO1 in iron-restricted medium (CAA medium), with or without 10 μM NOCA, 7 and analyzed the bacteria by proteomics to identify the TBDTs and any other proteins involved 8 in iron acquisition by NOCA ( Figure 2). 9 In the presence of NOCA, only the expression of the TBDT FoxA was strongly induced, 10 showing a log2 6.37-fold increase (Figure 2A).…”

Section: Introductionmentioning

confidence: 99%

“…9 These sensing 21 mechanisms involve cell surface signaling that involves the TBDT itself and coupled sigma and 22 anti-sigma factors FoxR/FoxI and FiuR/FiuI. 22,25 The various changes in protein conformation 23 and the protein interactions involved in these signaling cascades have been described in more 24 detail for the PVD pathway, with the FpvR/PvdS or FpvR/FpvI sigma/anti sigma factors. 25 Binding of iron-loaded PVD to the TBDT FpvA induces movement of the periplasmic N-1 10 42 M -1 for enterobactin, much higher than the affinities of PVD and PCH, the siderophores 2 produced by P. aeruginosa (10 18 M -2 for PCH 48 and 10 32 M -1 for PVD 49 ).…”

Section: Introductionmentioning

confidence: 99%

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Nocardamine-Dependent Iron Uptake in Pseudomonas aeruginosa: Exclusive Involvement of the FoxA Outer Membrane Transporter

et al. 2020

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Iron is a key nutrient for almost all living organisms. Paradoxically, it is poorly soluble and 3 consequently poorly bioavailable. Bacteria have thus developed multiple strategies to access 4 this metal. One of the most common consists of the use of siderophores, small compounds that chelate ferric iron with very high affinity. Many bacteria are able to produce their own 6 siderophores or use those produced by other microorganisms (exosiderophores) in a piracy 7 strategy. Pseudomonas aeruginosa produces two siderophores, pyoverdine and pyochelin, and 8 is also able to use a large panel of exosiderophores. We investigated the ability of P. aeruginosa 9 to use nocardamine (NOCA) and ferrioxamine B (DFOB) as exosiderophores under iron-10 limited planktonic growth conditions. Proteomic and RT-qPCR approaches showed induction 11 of the transcription and expression of the outer membrane transporter FoxA in the presence of 12 NOCA or DFO in the bacterial environment. Expression of the proteins of the heme-or 13 pyoverdine-and pyochelin-dependent iron uptake pathways was not affected by the presence 14 of these two tris-hydroxamate siderophores. 55 Fe uptake assays using foxA mutants showed 15 ferri-NOCA to be exclusively transported by FoxA, whereas ferri-DFOB was transported by 16 FoxA and at least one other unidentified transporter. The crystal structure of FoxA complexed 17 with NOCA-Fe revealed very similar siderophore binding sites between NOCA-Fe and DFOB-18 Fe. We discuss iron uptake by hydroxamate exosiderophores in P. aeruginosa cells in the light 19 of these results. 20 Page 2 of 40 ACS Paragon Plus Environment ACS Chemical Biology 1 detected the presence of ferri-exosiderophores, these transcriptional regulators activate the 2 transcription of the corresponding TBDT for iron acquisition. 9,22,29-32 3 Here, we investigated the ability of P. aeruginosa to use nocardamine (NOCA, Figure 1A) as 4 an exosiderophore. NOCA, also called desferrioxamine E, is a cyclic tris-hydroxamate 5 siderophore related to DFOB, with a higher affinity for iron: 10 32 M-1 for NOCA and 10 30 M-1 6 for DFOB 33 (Figure 1). NOCA is synthesized by various actinomycetes, such as Streptomyces, Nocardia, and Micromonospora, and bacteria, such as Streptomyces griseus, 35 Pseudomonas 8 stutzeri, 36 and Enterobacter agglomerans. 37 We show that the presence of NOCA in the P. 9 aeruginosa environment strongly induces the transcription and expression of foxA with the 10 same efficiency as DFOB. We demonstrate, using 55 Fe, that NOCA-55 Fe is exclusively 11 transported by the TBDT FoxA, whereas DFOB uses, in addition to FoxA, at least one other 12 transporter. We also determined the crystal structure of FoxA complexed with ferri-NOCA, 13 revealing a siderophore-binding site very similar to that of DFOB.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nocardamine-Dependent Iron Uptake in Pseudomonas aeruginosa: Exclusive Involvement of the FoxA Outer Membrane Transporter

et al. 2020

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“…In Pectobacterium carotovorum , three CLB nucleases termed carocins have been characterized. Two of the carocins, S1K (40 kDa) and carocin D (91 kDa) are DNases while the third, S2 (85 kDa) is a tRNAse ( Chuang et al, 2007 ; Chan et al, 2009 , 2011 ; Roh et al, 2010 ; Atanaskovic et al, 2020 ). In addition, two pectobacterial CLBs, pectocins M1 and M2 (both 29 kDa) have been characterized that possess cytotoxic domains homologous to that of colicin M and have been shown to similarly target lipid II ( Grinter et al, 2012b ).…”

Section: Colicin-like Bacteriocinsmentioning

confidence: 99%

Bacteriocins Targeting Gram-Negative Phytopathogenic Bacteria: Plantibiotics of the Future

et al. 2020

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Gram-negative phytopathogenic bacteria are a significant threat to food crops. These microbial invaders are responsible for a plethora of plant diseases and can be responsible for devastating losses in crops such as tomatoes, peppers, potatoes, olives, and rice. Current disease management strategies to mitigate yield losses involve the application of chemicals which are often harmful to both human health and the environment. Bacteriocins are small proteinaceous antibiotics produced by bacteria to kill closely related bacteria and thereby establish dominance within a niche. They potentially represent a safer alternative to chemicals when used in the field. Bacteriocins typically show a high degree of selectivity toward their targets with no off-target effects. This review outlines the current state of research on bacteriocins active against Gramnegative phytopathogenic bacteria. Furthermore, we will examine the feasibility of weaponizing bacteriocins for use as a treatment for bacterial plant diseases.

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Iron Homeostasis in Pseudomonas aeruginosa: Targeting Iron Acquisition and Storage as an Antimicrobial Strategy

Llamas

Sánchez-Jiménez

2022

Advances in Experimental Medicine and Biology

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Targeted Killing of Pseudomonas aeruginosa by Pyocin G Occurs via the Hemin Transporter Hur

Cited by 21 publications

References 31 publications

Nocardamine-Dependent Iron Uptake in Pseudomonas aeruginosa: Exclusive Involvement of the FoxA Outer Membrane Transporter

Nocardamine-Dependent Iron Uptake in Pseudomonas aeruginosa: Exclusive Involvement of the FoxA Outer Membrane Transporter

Bacteriocins Targeting Gram-Negative Phytopathogenic Bacteria: Plantibiotics of the Future

Iron Homeostasis in Pseudomonas aeruginosa: Targeting Iron Acquisition and Storage as an Antimicrobial Strategy

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