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Brucella

Brucella

For medical students3 min readUpdated 2026-10-10

Brucella is a genus of small, Gram-negative bacteria that cause brucellosis (undulant fever), a severe zoonotic infection. As facultative intracellular pathogens, they are capable of surviving inside macrophages for prolonged periods, which drives the chronic systemic nature of the disease.

MorphologySmall, non-spore-forming Gram-negative coccobacilli.
Target CellsCells of the reticuloendothelial system (lymph nodes, liver, spleen).
Bioterrorism ThreatAirborne transmission makes the pathogen a potential bioweapon.
CultivationExtremely slow growth: primary cultures require incubation for up to 30 days.

Taxonomy and Biological Properties

The genus Brucella includes 6 species, initially discovered by David Bruce in 1886. Three species are of primary epidemiological and clinical significance to humans: B. melitensis (the most virulent), B. abortus, and B. suis.

Morphologically, they are small, non-motile, non-spore-forming Gram-negative coccobacilli. Interestingly, these bacteria can form a capsule, but exclusively when grown on media supplemented with serum.

Brucellae are fastidious organisms. They require complex media enriched with blood, liver infusion, or tryptose-soy extract. Growth is extremely slow (up to a month). Metabolically, they are strict aerobes, though B. abortus requires an elevated carbon dioxide concentration (5%) for optimal growth. In liquid media, they produce uniform turbidity. Virulent strains form smooth (S) colonies, whereas avirulent variants form rough (R) colonies.

Biochemically, they are active: they produce urease, catalase, and oxidase, reduce nitrates, and oxidize carbohydrates without producing gas or acid. Hemolytic and proteolytic enzymes are absent. Species are differentiated based on hydrogen sulfide production (characteristic of B. abortus), dye sensitivity (thionin, basic fuchsin), and the ratio of somatic A and M antigens.

Epidemiology and Resistance

Brucellosis is a classic zoonotic infection. Infected humans do not transmit the disease to others. Animals serve as reservoirs, with each pathogenic species having a primary host preference:

Animals shed the bacteria into the environment via milk, urine, feces, and amniotic fluid. Humans contract the infection via the alimentary route (consuming unpasteurized milk or cheeses), direct contact with infected animals, or inhalation of infectious aerosols containing dust from contaminated wool or manure.

Brucella shows high resistance to low temperatures. It persists in soil and water for up to 4 months, in frozen meat for up to 5 months, and in unpasteurized milk cheeses for up to 8 weeks. However, brucellae are highly susceptible to heat (killed at 60 °C within 30 minutes, instantly at boiling point) and are rapidly destroyed by standard disinfectants.

Pathogenesis and Clinical Presentation

Brucella species are facultative intracellular parasites, and their virulence factors are tailored for intracellular survival within host cells. Adhesion to target cells occurs via binding to sialic acid residues. Invasion is mediated by outer membrane proteins, lipopolysaccharide (LPS), and a type IV secretion system that injects effector proteins directly into the host cell. Early on, the enzyme urease plays a critical role by protecting the bacterium from phagolysosomal destruction.

Following internalization by phagocytes, the bacteria survive and replicate intracellularly. Subsequently, they disseminate via lymphatic and blood vessels, seeding organs of the reticuloendothelial system. Intracellular parasitism leads to periodic bacteremic bursts.

The disease has an infectious-allergic component and tends toward chronicity with alternating remissions and relapses. Clinically, it manifests as prolonged fever and the formation of characteristic granulomas in the nervous, urogenital, and musculoskeletal systems. The immune response features non-sterile immunity and delayed-type hypersensitivity (DTH). Severe complications can include involvement of the central nervous system, heart, and death.

Microbiological Diagnostics and Prevention

Diagnosis of brucellosis relies on three pillars:

  1. Bacteriological («Gold Standard»): Culture of blood, cerebrospinal fluid, or lymph node aspirates must be performed in specialized high-security containment laboratories. Two bottles are typically used (one incubated in capnophilic conditions at 37 °C for up to 30 days, with subcultures performed every 5 days).
  2. Animal Inoculation: Used when the clinical sample has low bacterial load or is contaminated with other flora.
  3. Serological Testing: The primary clinical diagnostic modality. During the acute phase, Wright agglutination test, indirect hemagglutination, and ELISA are utilized. In subacute or latent phases, standard tests may be falsely negative due to incomplete blocking antibodies; thus, the Coombs test is applied. Screening methods include the rapid Huddleson slide agglutination test and the Burnet skin test to evaluate DTH.

Management relies on targeted antibiotic therapy. Specific prophylaxis is performed under strict epidemiological indications using a live attenuated vaccine derived from B. abortus strain 19-BA, which confers cross-protection against multiple Brucella species.

Mnemonic

Species and their hosts: B. melitensis (Melitensis = Mutton/Goats), B. abortus (Abortus = Abortion in cattle/Agro-cows), B. suis (Suis = Swine).

Frequently asked questions

Which antibiotics are the drugs of choice for the targeted therapy of brucellosis?

The drugs of choice for the targeted treatment of brucellosis are tetracyclines combined with other antimicrobial agents. Therapy requires the simultaneous administration of two drugs, at least one of which must be capable of penetrating host cell membranes.

Standard regimens include:

  • Doxycycline — combined with rifampin or streptomycin.
  • Rifampin — used alongside doxycycline or ofloxacin.
  • Tetracycline — used in combination with gentamicin or rifampin.

The course of treatment is prolonged (at least 6 weeks). Relapses require repeat courses with alternative drug combinations.

What is the Burnet test, what reagent is used, and how are the results interpreted?

The Burnet test is a delayed-type hypersensitivity skin test used to assess cellular sensitization to Brucella antigens. The diagnostic reagent utilized is brucellin, a specific protein allergen derived from the bacteria.

The reagent is injected intradermally, typically into the middle third of the volar surface of the forearm. Results are read 48 to 72 hours post-injection, with the presence and size of induration (papule) serving as the primary diagnostic metric.

What antigens comprise the antigenic structure of Brucella, and how are they distributed among species?

The antigenic profile of Brucella includes surface and somatic antigens, the relative proportions of which differ among species.

  • Surface antigen — capsular Vi-like antigen.
  • Somatic antigens — A antigen and M antigen.
SpeciesPredominant Somatic Antigen
B. melitensisM antigen
B. abortusA antigen
B. suisA antigen
Why might the Wright agglutination test yield false-negative results in latent brucellosis?

During the subacute phase and periods of remission, incomplete blocking antibodies (IgA and IgG) accumulate in the blood and inhibit standard agglutination. The Coombs antiglobulin test is used to detect these blocking antibodies.

What conditions are required to successfully isolate a pure culture of Brucella?

Brucellae are fastidious: they require complex media (enriched with blood or liver infusion), prolonged incubation of up to 30 days at 37 °C, and B. abortus specifically requires an atmosphere supplemented with 5% CO₂.

Is a human patient with brucellosis contagious to others?

No, an infected human is not a source of transmission. Brucellosis is a classic zoonosis; humans acquire the infection exclusively from animals or animal products.

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