Dataset Information

The Ton system, an ABC transporter, and a universally conserved GTPase are involved in iron utilization by Brucella melitensis 16M.

ABSTRACT: Brucella spp. are gram-negative intracellular facultative pathogens that are known to produce 2,3-dihydroxybenzoic acid (DHBA), a catechol siderophore that is essential for full virulence in the natural host. The mechanism of DHBA entry into Brucella and other gram-negative bacteria is poorly understood. Using mini-Tn5Kmcat mutagenesis, we created a transposon library of Brucella melitensis 16M and isolated 32 mutants with a defect in iron acquisition or assimilation. Three of these transposon mutants are deficient in utilization of DHBA. Analysis of these three mutants indicated that the ExbB, DstC, and DugA proteins are required for optimal assimilation of DHBA and/or citrate. ExbB is part of the Ton complex, and DstC is a permease homologue of an iron(III) ABC transporter; in gram-negative bacteria these two complexes are involved in the uptake of iron through the outer and inner membranes, respectively. DugA is a new partner in iron utilization that exhibits homology with the bacterial conserved GTPase YchF. Based on this homology, DugA could have a putative regulatory function in iron assimilation in Brucella. None of the three mutants was attenuated in cellular models or in the mouse model of infection, which is consistent with the previous suggestion that DHBA utilization is not required in these models.

SUBMITTER: Danese I

PROVIDER: S-EPMC517599 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature

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The Ton system, an ABC transporter, and a universally conserved GTPase are involved in iron utilization by Brucella melitensis 16M.

Danese Isabelle I Haine Valerie V Delrue Rose-May RM Tibor Anne A Lestrate Pascal P Stevaux Olivier O Mertens Pascal P Paquet Jean-Yves JY Godfroid Jacques J De Bolle Xavier X Letesson Jean-Jacques JJ

Infection and immunity 20041001 10

Brucella spp. are gram-negative intracellular facultative pathogens that are known to produce 2,3-dihydroxybenzoic acid (DHBA), a catechol siderophore that is essential for full virulence in the natural host. The mechanism of DHBA entry into Brucella and other gram-negative bacteria is poorly understood. Using mini-Tn5Kmcat mutagenesis, we created a transposon library of Brucella melitensis 16M and isolated 32 mutants with a defect in iron acquisition or assimilation. Three of these transposon m ...[more]

PMID: 15385478

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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

Dataset Information

The Ton system, an ABC transporter, and a universally conserved GTPase are involved in iron utilization by Brucella melitensis 16M.

Publications

The Ton system, an ABC transporter, and a universally conserved GTPase are involved in iron utilization by Brucella melitensis 16M.

Similar Datasets

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