Fun stories about Brucella: the “furtive nasty bug”
Introduction
Brucella was called “nasty” by Moreno and Moriyon in their commentary paper on the genomic sequence of Brucella melitensis published by DelVecchio and co-workers (DelVecchio et al., 2002, Moreno and Moriyon, 2002). Brucella is “furtive” as well. Unlike many other pathogenic bacteria, Brucella lacks obvious classical virulence factors such as capsules, fimbriae, flagella, exotoxins, exoenzymes including exoproteases, cytolysins, resistance forms, antigenic variation, plasmids and lysogenic phages. Further, Brucella is a facultative intracellular pathogen of both professional and non-professional phagocytic cells, hiding within the immune system from the immune system!
In the last decade, several technical improvements such as transposon mutagenesis, in vivo expression technology (IVET), differential fluorescence induction (DFI), and signature tagged mutagenesis (STM) have made it possible to analyze the molecular basis of microbial pathogenesis on a genome wide basis. In conjunction with the emerging discipline of cellular microbiology and its satellite techniques (confocal microscopy, etc.), the study of the host–pathogen relationships has progressed rapidly. The Brucella scientific community seized the opportunities offered by these powerful approaches to learn the secrets of the pathogenesis of their favorite bacterial pathogen.
The ever-increasing reports on the virulence determinants of Brucella have been reviewed recently (Boschiroli et al., 2001). Our team is very involved in the identification of virulence genes and in deciphering the virulence mechanisms of Brucella (Godfroid et al., 1998, Godfroid et al., 2000, Lestrate et al., 2000, Delrue et al., 2001). The purpose of this paper is not to make a complete survey of what has already been published by ourselves and others but, rather, to focus on three amazing and intriguing stories of Brucella that we discovered and are presently investigating further: communication by quorum sensing, flagellar apparatus without motility, and cell cycle regulation.
Section snippets
To communicate or not to communicate: the quorum sensing story
A novel communication circuit called quorum sensing (QS) that is involved in the regulation of virulence gene expression among diverse bacterial species and dependent on the number of cells was described recently (Fuqua et al., 2001). Quorum sensing describes a phenomenon in which the accumulation of a signal or actor molecule called a pheromone allows individual cells to perceive when a minimum bacteria number or quorum is reached. The signal allows for the initiation of a concerted response
To move or to secrete: the story of the flagellar gene clusters in Brucella
Eighty percent of the known bacterial species are flagellated. Assembly of a flagellum and the taxis system require around 50 genes and 1% of the energy of the cell (Macnab, 1996). Search for a favorable niche is the obvious function of flagellum based mobility but, in pathogenic bacteria, this structure could also play a role in colonization or adhesion. The homology between subunits that form the protein transport apparatus of the flagellum and the contact dependent type III secretion
Peculiarities of the cell cycle control in Brucella: the CtrA regulon story
The ctrA gene (cell cycle transcriptional regulator A) identified first in the asymmetrically dividing α-Proteobacterium C. crescentus (Quon et al., 1996) encodes an essential response regulator belonging to the OmpR family of two-component signal transduction proteins (Volz, 1993). In C. crescentus, CtrA is a global regulator that orchestrates many cell cycle events through the transcriptional control of about one fourth of the cell cycle-regulated genes (Laub et al., 2000): (1) CtrA represses
Conclusion
We are still far from understanding the regulation and the fine tuning of the molecular mechanisms of Brucella and, finally, how this bacteria causes brucellosis. Not all virulence factors are known and, for those that are known, the cellular targets they interact with or interfere with still need to be identified. One of the ways will be to identify the common mechanisms shared with plant pathogens and endosymbionts of the α-Proteobacteria because genes involved in the virulence of A.
Acknowledgements
This work was supported by the Commission of the European Communities, contract no. QLK2-CT-1999-00014. R.-M. Delrue, B. Taminiau, I. Danese, F. Bellefontaine, D. Fretin, A. Dricot, C. Deschamps and S. Leonard received a specialization grant from the Fonds pour la Formation à la Recherche dans l’Industrie et l’Agriculture.
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