DECIPHERING NEUROTROPIC MECHANISMS OF BURKHOLDERIA SPECIES: GENOMIC INSIGHTS AND MURINE MODEL DEVELOPMENT

Neuromelioidosis, a severe but underrecognized manifestation of Burkholderia pseudomallei infection, is associated with high mortality and often mimics neurological disorders such as Guillain–Barré syndrome and brainstem encephalitis, resulting in diagnostic challenges in endemic regions. With increasing prevalence in India and other tropical countries, the neurotropic mechanisms and host–pathogen interactions underlying this disease remain poorly understood. This study aimed to define the genetic and phenotypic determinants of neurovirulence and establish experimental models to investigate infection dynamics. Clinical Burkholderia isolates were characterized using phenotypic profiling, antimicrobial susceptibility testing, and whole‑genome sequencing to identify virulence factors, antimicrobial resistance determinants, and genetic diversity, with emphasis on Indian sequence types. In vitro infection assays using neuronal and epithelial cell lines demonstrated marked strain‑specific differences in invasion efficiency, intracellular persistence, and cytotoxicity. To establish a reproducible in vivo framework, Burkholderia cepacia infection was modeled in C57BL/6J mice, enabling assessment of bacterial dissemination, behavioral alterations, and organ‑specific persistence during acute and chronic infection stages. Analysis of behavioral outcomes and bacterial burden confirmed the robustness of this murine model for studying neurotropic Burkholderia infections. Preliminary observations indicate that host responses, including apoptosis and lipid droplet formation, vary depending on bacterial strain and infected cell type. Overall, this integrated genomic, cellular, and in vivo approach provides a foundation for future B. pseudomallei investigations under BSL‑3 containment and advances understanding of immune‑mediated disease progression, with potential implications for improved diagnosis and targeted therapies in endemic regions.