Host and Pathogen Genetic Determinants of Brucellosis in Veterinary-One Health Interface: A Review

Brucellosis remains among the most widespread global zoonoses, yet its genetic architecture-spanning host susceptibility and pathogen virulence-is increasingly being investigated. Advances in whole-genome sequencing, transposon mutagenesis, CRISPR screening, and machine learning-driven transcriptomics have accelerated marker discovery on both sides of the host-pathogen interface, although most signatures remain at discovery or early-validation stages. In hosts, polymorphisms in innate immune receptors (TLR2, TLR5, VDR), cytokine regulators (TNF, CTLA4), and novel candidates such as ASAP1 are linked to differential susceptibility in humans and livestock. In Brucella, functional genomics shows that virulence relies on interconnected regulatory circuits that control the type IV secretion system, lipopolysaccharide biosynthesis, and stress responses, with gene essentiality shifting according to the host immune context. Antimicrobial resistance may involve unconventional mechanisms, including metabolic and regulatory adaptation, that are not fully explained by classical resistance-gene paradigms and may implicate metabolic reprogramming and ribosomal modulation. This review synthesizes these converging lines of evidence, highlights key gaps-chiefly the scarcity of functional validation for host associations and limited multi-omics integration-and proposes a roadmap for translating genetic markers toward future diagnostic refinement and therapeutic target discovery, urging a shift from descriptive cataloging toward mechanistic and clinical validation.