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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Batista, Bianca Bontempi [1] ; Rodrigues de Souza Santos, Renato Elias [1] ; Ricci-Azevedo, Rafael [1] ; Silva Neto, Jose Freire [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Infection and Immunity; v. 87, n. 12 DEC 2019.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 18/01388-6 - Homeostase de ferro em Chromobacterium violaceum: mecanismos regulatórios, sistemas de captação e papel em virulência
Beneficiário:José Freire da Silva Neto
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/20435-9 - Fatores de transcrição de Chromobacterium violaceum: integrando vias de sinalização, regulons e patogenicidade
Beneficiário:José Freire da Silva Neto
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 17/03342-0 - Fatores de transcrição da família Fur e a resposta a ferro e zinco em Chromobacterium violaceum
Beneficiário:Renato Elias Rodrigues de Souza Santos
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 17/02998-0 - Efeitos de Toxoplasma gondii e Paracoccidioides brasiliensis, exercidos através de suas respectivas lectinas sobre vias intracelulares ativadas pelo reconhecimento de glicanos N-ligados a receptores do tipo Toll em neutrófilos
Beneficiário:Rafael Ricci de Azevedo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado