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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Production and Uptake of Distinct Endogenous Catecholate-Type Siderophores Are Required for Iron Acquisition and Virulence in Chromobacterium violaceum

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Batista, Bianca Bontempi [1] ; Rodrigues de Souza Santos, Renato Elias [1] ; Ricci-Azevedo, Rafael [1] ; Silva Neto, Jose Freire [1]
Total Authors: 4
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Infection and Immunity; v. 87, n. 12 DEC 2019.
Web of Science Citations: 0

Bacteria use siderophores to scavenge iron from environmental or host sources. The iron acquisition systems of Chromobacterium violaceum, a ubiquitous environmental bacterium that can cause infections in humans, are still unknown. In this work, we demonstrated that C. violaceum produces putative distinct endogenous siderophores, here named chromobactin and viobactin, and showed that they are each required for iron uptake and virulence. An in silico analysis in the genome of C. violaceum revealed that genes related to synthesis and uptake of chromobactin (cba) and viobactin (vba) are located within two secondary-metabolite biosynthetic gene clusters. Using a combination of gene deletions and siderophore detection assays, we revealed that chromobactin and viobactin are catecholate siderophores synthesized from the common precursor 2,3-dihydroxybenzoate (2,3-DHB) on two nonribosomal peptide synthetase (NRPS) enzymes (CbaF and VbaF) and taken up by two TonB-dependent receptors (CbuA and VbuA). Infection assays in mice revealed that both the synthesis and the uptake of chromobactin or viobactin are required for the virulence of C. violaceum, since only the mutant strains that do not produce any siderophores or are unable to take up both of them were attenuated for virulence. In addition, the mutant strain unable to take up both siderophores showed a pronounced attenuation of virulence in vivo and reduced neutrophil extracellular trap (NET) formation in in vitro assays, suggesting that extracellularly accumulated siderophores modulate the host immune response. Overall, our results revealed that C. violaceum uses distinct endogenous siderophores for iron uptake and its establishment in the host. (AU)

FAPESP's process: 18/01388-6 - Iron homeostasis in Chromobacterium violaceum: regulatory mechanisms, uptake systems and role in virulence
Grantee:José Freire da Silva Neto
Support type: Regular Research Grants
FAPESP's process: 12/20435-9 - Transcription factors of Chromobacterium violaceum: integrating signaling pathways, regulons and pathogenicity
Grantee:José Freire da Silva Neto
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 17/03342-0 - The Fur family of transcription factors and the response to iron and zinc in Chromobacterium violaceum
Grantee:Renato Elias Rodrigues de Souza Santos
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/02998-0 - Effects of Toxoplasma gondii and Paracoccidioides brasiliensis, exerted through their respective lectins on intracellular pathways activated by the recognition of N-linked glycans to toll like receptors on neutrophils
Grantee:Rafael Ricci de Azevedo
Support type: Scholarships in Brazil - Post-Doctorate