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Controlling a Necessary Evil: Quorum Sensing Attenuates Virulence in Sodalis praecaptivus.

ABSTRACT: Sodalis praecaptivus is a close relative and putative environmental progenitor of the widely distributed, insect-associated, Sodalis-allied symbionts. Mutant strains of S. praecaptivus, lacking critical components of a quorum sensing (QS) apparatus acquire a rapid and potent killing phenotype following microinjection into an insect host. Transcriptomic and genetic analyses indicate that insect killing occurs as a consequence of virulence factors, including insecticidal toxins and enzymes that degrade the insect integument that are normally repressed by QS at high infection densities. This unorthodox method of regulation ensures that virulence factors are only utilized to initiate the insect-bacterial association. Once bacteria reach a sufficient infection density in host tissues, the QS circuit represses the expression of these harmful genes, facilitating a long-lasting and benign association. We discuss the implications of the functionality of this QS system in the context of the establishment and evolution of mutualistic relationships involving these bacteria.

ORGANISM(S): Sodalis praecaptivus

PROVIDER: GSE97720 | GEO | 2017/05/09

SECONDARY ACCESSION(S): PRJNA382726

REPOSITORIES: GEO

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Project description:Many pathogenic bacteria use a regulatory process termed Quorum Sensing (QS) to produce and detect small diffusible molecules to synchronize gene expression within a population. In Gram-negative bacteria, the detection and response to these molecules depend on transcriptional regulators belonging to the LuxR family. Such a system have been discovered in the intracellular pathogen Brucella melitensis, a Gram-negative bacteria responsible for brucellosis, a word-wide zoonosis remaining a serious public health concern in endemic countries. Two LuxR-type regulators, VjbR and BabR, have been identified in the genome of this pathogen. The vjbR mutant is highly attenuated in all tested models suggesting a crucial role of QS in the virulence of Brucella. This attenuation is at least due to the involvement of VjbR in the activation of the virB operon coding for a type four secretion system essential for Brucella to reach its intracellular replication compartment. At present, no function has been attributed to BabR. To assess the role of both Brucella QS-regulators, we performed in tandem comparative transcriptomic and proteomic analyses of vjbR and babR mutants. These experiments revealed that 10% of Brucella genome is regulated through those regulators, revealing that QS is a global regulatory system in this intracellular pathogen. The overlapping between BabR and VjbR targets suggest an unexpected cross-talk between these two regulators. Moreover, our results demonstrate that VjbR and BabR regulate many gene and/or proteins involved in stress response, metabolism and virulence. These targets are potentially involved in the adaptation of Brucella to the oxidative, pH and nutritional stresses encountered within the host. These findings highlight the involvement of QS in the virulence of Brucella and led us to suggest that this regulatory system could be implied in the spatial and sequential adaptation of Brucella to the host environment. Keywords: Quorum Sensing, Comparative gene expression, Brucella melitensis

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Controlling a Necessary Evil: Quorum Sensing Attenuates Virulence in Sodalis praecaptivus.

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