Brucella

Ni-Urease—Gateway to Infection#

Urease is essential for survival during gastrointestinal passage and initial intestinal colonization.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓}

Brucella is typically acquired through ingestion of contaminated dairy products or direct contact with infected animals. The oral route demands acid resistance during gastric transit.

Urease-generated ammonia and bicarbonate buffer the Acidic Microenvironment of the stomach, enabling bacteria to reach the intestinal mucosa intact. Once past the GI barrier, Brucella establishes intracellular infection in macrophages, where it resides in a modified phagosome.

Urease as Vaccine Target#

Immunization with urease protects against Brucella infection—one of the clearest demonstrations that a nickel (Ni)-dependent virulence factor can serve as a protective antigen.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓}

This validates urease as a targetable vulnerability, paralleling the HspA vaccine candidate approach for Helicobacter pylori. The finding has broader implications: any pathogen whose colonization depends on urease-mediated acid survival could be targeted with urease-based immunization strategies.

Iron Acquisition#

Brucella species produce siderophores (brucebactin) for iron scavenging within the macrophage phagosome.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓} Iron acquisition is critical for intracellular survival and replication, complementing the nickel-dependent acid survival that enables initial colonization.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓}

Clinical Significance#

Brucellosis: causes undulant fever, arthritis, endocarditis, neurobrucellosis. Over 500,000 new human cases annually worldwide.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓} Zoonotic reservoir: cattle (B. abortus), goats/sheep (B. melitensis), swine (B. suis), dogs (B. canis).^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓}

Intracellular persistence: survives within macrophages by preventing phagosome-lysosome fusion, creating chronic and relapsing infections.^{[1]Role of Nickel in Microbial PathogenesisRobert J. Maier, Stéphane L. Benoit · 2019Open reference 1 ↓} Occupational and food-borne: pasteurization of dairy products is the primary prevention strategy; absence of pasteurization in endemic regions drives ongoing transmission.

Treatment requires prolonged combination antibiotic therapy (doxycycline + streptomycin/rifampin), and relapse rates remain significant.