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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.)

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

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Author(s):
Previato-Mello, Maristela ; Meireles, Diogo de Abreu ; Soares Netto, Luis Eduardo ; da Silva Neto, Jose Freire
Total Authors: 4
Document type: Journal article
Source: Infection and Immunity; v. 85, n. 8 AUG 2017.
Web of Science Citations: 7
Abstract

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)

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: 12/21722-1 - Structural and biochemical characterization of Ohr/OsmC family proteins: emphasis on the characterization of a Francisella tularensis protein involved in pathogenicity
Grantee:Diogo de Abreu Meireles
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/25745-9 - Functional characterization of MarR family transcription factors in Chromobacterium violaceum
Grantee:Maristela Previato Mello
Support type: Scholarships in Brazil - Doctorate