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

Autor(es)

Batista, Bianca Bontempi ^[1] ; Rodrigues de Souza Santos, Renato Elias ^[1] ; Ricci-Azevedo, Rafael ^[1] ; Silva Neto, Jose Freire ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto, SP - Brazil

• 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
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - 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
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado