FrpA is the outer membrane piscibactin transporter in Vibrio anguillarum: structural elements in synthetic piscibactin analogues required for transport

Autor: Diana Martínez-Matamoros, Lucía Ageitos, Jaime Rodríguez, Marta A. Lages, Miguel Balado, Carlos Jiménez, Manuel L. Lemos, M. Carmen de la Fuente
Rok vydání: 2021
Předmět:
Zdroj: RUC. Repositorio da Universidade da Coruña
instname
ISSN: 1432-1327
0949-8257
DOI: 10.1007/s00775-021-01916-1
Popis: Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG [Abstract] Piscibactin (Pcb) is a labile siderophore widespread among Vibrionaceae. Its production is a major virulence factor of some fish pathogens such as Photobacterium damselae subsp. piscicida and Vibrio anguillarum. Although FrpA was previously suggested as the putative outer membrane transporter (OMT) for ferri-piscibactin, its role in piscibactin uptake was never demonstrated. In this work, we generated mutants of V. anguillarum defective in FrpA and analyzed their ability to use piscibactin as iron source. The results showed that inactivation of frpA completely disables piscibactin utilization, and the original phenotype could be restored by gene complementation, confirming that FrpA is the OMT that mediates ferri-Pcb uptake. Additionally, the ability of several Pcb thiazole analogues, with different configurations at positions 9, 10, and 13, to be internalized through FrpA, was evaluated measuring their ability to promote growth under iron deficiency of several indicator strains. The results showed that while those analogues with a thiazole ring maintain almost the same activity as Pcb, the maintenance of the hydroxyl group present in natural piscibactin configuration at position C-13 is crucial for Fe³⁺ chelation and, in consequence, for the recognition of the ferri-siderophore by the cognate OMT. All these findings allowed us to propose a Pcb analogue as a good candidate to vectorize antimicrobial compounds, through the Trojan horse strategy, to develop novel compounds against bacterial fish diseases. This work was supported by grants RTI2018-093634-B-C21/C22 (AEI/FEDER, EU), cofunded by the FEDER Programme from the European Union, and by Grant PID2019-103891RJ-100 (AEI) from the Agency for Research (AEI) of Spain. Work in University of Santiago de Compostela and University of A Coruña was also supported by grants GRC2018/018 and GRC2018/039, respectively, from Xunta de Galicia and BLUEBIOLAB (0474_BLUEBIOLAB_1_E), Programme INTERREG V A of Spain-Portugal (POCTEP). L.A. thanks Xunta de Galicia (Spain) for a predoctoral fellowship (ED481A-2019/081) co-financed by European Social Fund (ESF). Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature Xunta de Galicia; GRC2018/018 Xunta de Galicia; GRC2018/039 Xunta de Galicia; ED481A-2019/081
Databáze: OpenAIRE
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