Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum

Autor(es)

Previato-Mello, Maristela ; Meireles, Diogo de Abreu ; Soares Netto, Luis Eduardo ; da Silva Neto, Jose Freire

• Tipo de documento: Artigo Científico
• Fonte: Infection and Immunity; v. 85, n. 8 AUG 2017.
• Citações Web of Science: 7

Resumo

A major pathway for the detoxification of organic hydroperoxides, such as cumene hydroperoxide (CHP), involves the MarR family transcriptional regulator OhrR and the peroxidase OhrA. However, the effect of these peroxides on the global transcriptome and the contribution of the OhrA/OhrR system to bacterial virulence remain poorly explored. Here, we analyzed the transcriptome profiles of Chromobacterium violaceum exposed to CHP and after the deletion of ohrR, and we show that OhrR controls the virulence of this human opportunistic pathogen. DNA microarray and Northern blot analyses of CHP-treated cells revealed the upregulation of genes related to the detoxification of peroxides (antioxidant enzymes and thiol-reducing systems), the degradation of the aromatic moiety of CHP (oxygenases), and protection against other secondary stresses (DNA repair, heat shock, iron limitation, and nitrogen starvation responses). Furthermore, we identified two upregulated genes (ohrA and a putative diguanylate cyclase with a GGDEF domain for cyclic di-GMP {[}c-di-GMP] synthesis) and three downregulated genes (hemolysin, chitinase, and collagenase) in the ohrR mutant by transcriptome analysis. Importantly, we show that OhrR directly repressed the expression of the putative diguanylate cyclase. Using a mouse infection model, we demonstrate that the ohrR mutant was attenuated for virulence and showed a decreased bacterial burden in the liver. Moreover, an ohrRdiguanylate cyclase double mutant displayed the same virulence as the wild-type strain. In conclusion, we have defined the transcriptional response to CHP, identified potential virulence factors such as diguanylate cyclase as members of the OhrR regulon, and shown that C. violaceum uses the transcriptional regulator OhrR to modulate its virulence. (AU)

• Processo FAPESP: 13/25745-9 - Caracterização funcional de fatores de transcrição da família MarR de Chromobacterium violaceum
• Beneficiário: Maristela Previato Mello
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/21722-1 - Caracterização estrutural e bioquímica de proteínas da família Ohr/OsmC: ênfase para a caracterização de uma proteína de Francisella tularensis envolvida em patogenicidade
• Beneficiário: Diogo de Abreu Meireles
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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