Brucellosis is a worldwide disease of humans and livestock that is caused by a number of very closely related classical Brucella species in the alpha-2 subdivision of the Proteobacteria. We report the complete genome sequence of Brucella abortus field isolate 9-941 and compare it to those of Brucella suis 1330 and Brucella melitensis 16 M. The genomes of these Brucella species are strikingly similar, with nearly identical genetic content and gene organization. However, a number of insertion-deletion events and several polymorphic regions encoding putative outer membrane proteins were identified among the genomes. Several fragments previously identified as unique to either B. suis or B. melitensis were present in the B. abortus genome. Even though several fragments were shared between only B. abortus and B. suis, B. abortus shared more fragments and had fewer nucleotide polymorphisms with B. melitensis than B. suis. The complete genomic sequence of B. abortus provides an important resource for further investigations into determinants of the pathogenicity and virulence phenotypes of these bacteria.Brucellosis is a bacterial disease of animals that can be transmitted to humans. The primary impact of brucellosis stems from losses due to reproductive failure in food animals and the loss of human productivity. Since brucellosis threatens the food supply and causes undulant fever, a long, debilitating disease in humans, Brucella species are recognized as potential agricultural, civilian, and military bioterrorism agents. Brucellosis in food animals is controlled by vaccination. Human brucellosis is treatable with antibiotics, though the course of antibiotic treatment must be prolonged due to the intracellular nature of Brucella.Analysis of 16S rRNA sequences places Brucella spp. as members of the alpha-2 Proteobacteria (31). The genus Brucella has six recognized species, all of which exhibit distinct host preferences (25,26). The high degree of similarity among the brucellae (1, 3, 13, 33) lends support to the proposal that the classical species of Brucella are actually strains of Brucella melitensis (40). However, this view conflicts with the hypothesized evolutionary isolation of these classical species due to their intracellular existence and host preference (29). Common host-pathogen associations among the classical Brucella species are as follows: B.

Fifty years ago, bacteria in the genus Brucella were known to cause infertility and reproductive losses. At that time, the genus was considered to contain only 3 species: Brucella abortus, Brucella melitensis, and Brucella suis. Since the early 1960s, at least 7 new species have been identified as belonging to the Brucella genus (Brucella canis, Brucella ceti, Brucella inopinata, Brucella microti, Brucella neotomae, Brucella ovis, and Brucella pinnipedialis) with several additional new species under consideration for inclusion. Although molecular studies have found such high homology that some authors have proposed that all Brucella are actually 1 species, the epidemiologic and diagnostic benefits for separating the genus based on phenotypic characteristics are more compelling. Although pathogenic Brucella spp have preferred reservoir hosts, their ability to infect numerous mammalian hosts has been increasingly documented. The maintenance of infection in new reservoir hosts, such as wildlife, has become an issue for both public health and animal health regulatory personnel. Since the 1960s, new information on how Brucella enters host cells and modifies their intracellular environment has been gained. Although the pathogenesis and histologic lesions of B. abortus, B. melitensis, and B. suis in their preferred hosts have not changed, additional knowledge on the pathology of these brucellae in new hosts, or of new species of Brucella in their preferred hosts, has been obtained. To this day, brucellosis remains a significant human zoonosis that is emerging or reemerging in many parts of the world.Keywords Brucella, pathogenesis, zoonosis, reservoir hosts, laboratory modelsIn 1966, the first issue of Pathologia Veterinaria-now known as Veterinary Pathology-published an article on the characteristics of Brucella granulomas by K. L. Jacob, and the third issue included a manuscript by B. I. Osburn and P. C. Kennedy describing pathologic and immunologic responses of fetal lambs after infection with Brucella ovis. As the journal embarks on its second half-century of publication, it seems appropriate to assess the advancement of knowledge on this topic since these articles were published in the first issues of the journal.Fifty years ago, bacteria in the genus Brucella were known to cause infertility and reproductive losses with predilection for causing placentitis, fetal pneumonia, and mastitis. At that time, the genus contained only Brucella abortus, Brucella melitensis, and Brucella suis, the 3 classic species of brucellae, and these were generally thought to be somewhat hostspecific pathogens of cattle, sheep and goats, and swine, respectively. They were also known to be zoonotic, with the capability for causing clinical disease in humans. At that time, taxonomy placed the 3 classic species in the family Brucellaceae, with other bacterial genera such as Bordetella, Pasteurella and so on. Although scientific and practical knowledge of brucellosis has increased dramatically, in many countries, brucellosis continu...

Brucellosis, in particular infections with Brucella abortus, Brucella melitensis or Brucella suis, remains a significant human health threat in many areas of the world. The persistence of pathogenic Brucella spp. in domestic livestock or free-ranging wildlife remains unresolved, despite decades of regulatory efforts worldwide. Although vaccination is probably the most economic control measure, administration of currently available vaccines alone is not sufficient for elimination of brucellosis in any host species. Complacency in brucellosis control programs usually results in failure, or at best, limited reductions in disease prevalence or incidence of human infections. New brucellosis vaccines with high efficacy and safety are needed that address the diversity in host species and can be more widely applied under field conditions. Development of safer and more efficacious vaccines alone, or combined with enhancements or increased emphasis on other regulatory program components, could have tremendous impact on reducing the worldwide prevalence of brucellosis and the associated zoonotic infections.

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Brucella suis is a significant zoonotic species that is present in domestic livestock and wildlife in many countries worldwide. Transmission from animal reservoirs is the source of human infection as human-to-human transmission is very rare. Although swine brucellosis causes economic losses in domestic livestock, preventing human infection is the primary reason for its emphasis in disease control programs. Although disease prevalence varies worldwide, in areas outside of Europe, swine brucellosis is predominantly caused by B. suis biovars 1 and 3. In Europe, swine are predominantly infected with biovar 2 which is much less pathogenic in humans. In many areas worldwide, feral or wild populations of swine are important reservoir hosts. Like other Brucella spp. in their natural host, B. suis has developed mechanisms to survive in an intracellular environment and evade immune detection. Limitations in sensitivity and specificity of current diagnostics require use at a herd level, rather for individual animals. There is currently no commercial vaccine approved for preventing brucellosis in swine. Although not feasible in all situations, whole-herd depopulation is the most effective regulatory mechanism to control swine brucellosis.

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The objective of this study was to develop a suitable experimental model of natural Mycobacterium bovis infection in white-tailed deer (Odocoileus virginianus), describe the distribution and character of tuberculous lesions, and to examine possible routes of disease transmission. In October 1997, 10 mature female white-tailed deer were inoculated by intratonsilar instillation of 2 x 10(3) (low dose) or 2 x 10(5) (high dose) colony forming units (CFU) of M. bovis. In January 1998, deer were euthanatized, examined, and tissues were collected 84 to 87 days post inoculation. Possible routes of disease transmission were evaluated by culture of nasal, oral, tonsilar, and rectal swabs at various times during the study. Gross and microscopic lesions consistent with tuberculosis were most commonly seen in medial retropharyngeal lymph nodes and lung in both dosage groups. Other tissues containing tuberculous lesions included tonsil, trachea, liver, and kidney as well as lateral retropharyngeal, mandibular, parotid, tracheobronchial, mediastinal, hepatic, mesenteric, superficial cervical, and iliac lymph nodes. Mycobacterium bovis was isolated from tonsilar swabs from 8 of 9 deer from both dosage groups at least once 14 to 87 days after inoculation. Mycobacterium bovis was isolated from oral swabs 63 and 80 days after inoculation from one of three deer in the low dose group and none of four deer in the high dose group. Similarly, M. bovis was isolated from nasal swabs 80 and 85 days after inoculation in one of three deer from the low dose group and 63 and 80 days after inoculation from two of four deer in the high dose group. Intratonsilar inoculation with M. bovis results in lesions similar to those seen in naturally infected white-tailed deer; therefore, it represents a suitable model of natural infection. These results also indicate that M. bovis persists in tonsilar crypts for prolonged periods and can be shed in saliva and nasal secretions. These infected fluids represent a likely route of disease transmission to other animals or humans.