Brucellosis: Bacteriology, pathogenesis, epidemiology and role of the metallophores in virulence: a review

Abstract

Brucellosis is a recognized zoonotic disease caused by various Brucella species with significant economic and animal welfare ramifications worldwide. The spread of brucellosis from domestic livestock and wild animals, as well as its emergence in new regions, present novel epidemiological challenges. The consumption of unpasteurized milk and dairy products from unsanitary farms in endemic areas poses a serious risk to public health from brucellosis. Determining the accurate prevalence of brucellosis, particularly in regions with persistently high prevalence, basically requires careful and frequent surveillance. Furthermore, transmission and detection of the illness in non-endemic areas have become more complex due to global human and animal migration as well as the trade in animal products. This review presents an updated understanding of brucellosis, covering its classification and taxonomy, pathogenesis, diagnosis and treatment approaches, epidemiology, available control and prevention measures, antimicrobial resistance and the role of metal uptake in bacterial virulence. It highlights the consequences of brucellosis for global health and underscores the need for continuous research, knowledge sharing, and interdisciplinary cooperation for effective disease control and prevention.

Keywords: Brucella; brucellosis; livestock; public health threats; zoonotic disease.

Figure 1

Schematic illustration of the Brucella cell wall.

Figure 2

Through lipid rafts, Brucella interacts with macrophage cell membranes to penetrate host cells and produce Brucella-containing vacuoles (BCV), which are encircled by phagocytic vesicles. Eight to twelve hours after Brucella enters the cell, the virus (BCV) develops the endosomes in the membrane-bound vacuoles, creates acidified endosomes, and receives certain host marker molecules by contact with lysosomes (Lys) and endosomes. Currently, endosomal Brucella containing vacuole (eBCV) is the term used to refer to BCV. The Type IV secretory system (T4SS) receives membranes derived from the Golgi apparatus and the endoplasmic reticulum (ER) by mediating the connection between the effector protein and the ER exit site as BCV grows and matures. The eBCV acquired Lys marker molecules (such Rab7, LAMP-1, etc.) after losing the early host marker molecules.

Figure 3

Factors related to Brucella virulence that affect macrophages’ ability to adjust the host immunological response. ∣, inhibition; →, activation. The dashed arrow shows that while the Brucella LPS produces a reduced inflammatory response, it does not signal through the TLR4 pathway robustly. The red X means that TLR5 does not identify the Brucella flagellin.

Figure 4

Factors associated with Brucella virulence that affect dendritic cells’ capacity to control the host immunological response. ∣, inhibition. The dashed arrow shows that while the Brucella LPS produces a reduced inflammatory response, it does not signal through the TLR4 pathway robustly.

Figure 5

The contributions of various components such as the T4SS effectors, the LPS O-chain, Omp22, Omp25d, and cyclic β-1,2-Dglucan (CbG) are pivotal in the formation of the replicative Brucella-containing vacuole within host macrophages. The membrane vesicles, depicted as empty black and orange circles, are involved in trafficking from the endolysosomal pathway, endoplasmic reticulum, and Golgi apparatus towards the Brucella-containing vacuoles (BCVs).

Figure 6

Siderophores produced by Brucella.

Figure 7

Siderophores-Iron transporters in Brucella. OM, outer membrane; IM, inner membrane.

Figure 8

Heme transporter in Brucella. OM, outer membrane; IM, inner membrane.

Figure 9

Iron transporter in Brucella. OM, outer membrane; IM, inner membrane.

Figure 10

Nickel, zinc, manganese, magnesium and cobalt transporters in Brucella. OM, outer membrane; IM, inner membrane.