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Brucella spp.

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Brucellosis

3. Introduction

Brucella species are gram-negative, facultative intracellular bacteria that cause brucellosis (or called Malta fever, undulant fever, Bang's disease, Mediterranean fever ) in humans and a variety of animals (Corbel, 1997). B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. The first three species have been identified as priority agents amenable for use in biological warfare and bio-terrorism, and are listed as NIAID and CDC category B priority pathogens. To date, there is no safe, effective Brucella vaccine available for human use. The vaccine strains used in animals are considered to be too virulent and unsafe for humans (Schurig et al., 1991). Novel vaccines that are non-infectious to humans but effective in stimulating a broad protective immune response are needed.

4. Microbial Pathogenesis

The mechanism of Brucella pathogenesis and infection of natural animal hosts is not completely understood (Corbel, 1997). It is well accepted that its pathogenesis relies on its ability to live and replicate inside the vacuolar phagocytic compartment of macrophages (Kohler et al., 2002). The host macrophage-Brucella interaction is critical for establishment of chronic Brucella infections. The Type IV secretion system encoded by the virB operon and the two-component regulatory system encoded by the bvrRS operon are required for successful replication of Brucella in macrophages. Smooth Brucella strains with intact lipopolysaccharide (LPS) O-side chains are virulent and invade macrophages through lipid rafts. On entry into the macrophage, Brucella reside in an acidified compartment that fuses with components of the early endosomal pathway. The majority of Brucella die at the early infection stage. A subpopulation of virulent Brucella strains is trafficked to an intracellular compartment known as the replicative phagosome (brucellosome) through continual interactions between the Brucella-containing vacuoles and the endoplasmic reticulum of the host macrophages. Once inside the replicative phagosome, Brucella are resistant to further attack and rapidly propagate. Virulent Brucella also inhibit macrophage apoptosis that in turn favors pathogen survival and replication. Brucella also infects placental trophoblast cells where acute infection leads to abortion and disease transmission (Roop et al., 2004).

5. Host Ranges and Animal Models

Brucella has a broad host range infecting vertebrate animal species and humans. Brucella infections are most often identified in humans, cattle, swine, goats, sheep, deer, caribou, elk, dogs and coyotes. There are six Brucella species based on the preferential host specificity: B. melitensis (goats), B. abortus (cattle), B. suis (swine), B. canis (dogs), B. ovis (sheep) and B. neotomae (desert mice). The first four species are pathogenic and exhibit a decreasing order of severity in humans. Therefore, brucellosis is a zoonotic disease (Corbel, 1997). Mouse models are often used in Brucella vaccine research. BALB/c and C57BL/10 mice differ in their abilities to induce immune responses and protection against virulent Brucella infections (Fernandes et al., 1996; Li, 1991; Montaraz et al., 1986).

6. Host Protective Immunity

Both humoral and cell-mediated immune responses can influence the course of a Brucella infection, cell-mediated immune responses are essential for clearance of intracellular Brucella (Schurig et al., 2002).

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