Cycle-Inhibiting Factor Is Associated with Burkholderia pseudomallei Invasion in Human Neuronal Cells

Amporn Rungruengkitkun1, Niramol Jitprasutwit2,3, Watcharamat Muangkaew1

  • 1Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

Biology
|October 27, 2022
PubMed

Insights

Burkholderia pseudomallei invades human neuronal cells, replicating and forming cell-to-cell spread structures. The virulence factor Cif is crucial for this invasion, offering potential therapeutic targets for neurological melioidosis.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Neuroscience

Background:

  • Burkholderia pseudomallei causes melioidosis, a severe human infection with high mortality.
  • The pathogenic mechanisms of B. pseudomallei, particularly in neurological contexts, remain poorly understood.

Purpose of the Study:

  • To investigate the interaction of B. pseudomallei with human neuronal cells.
  • To elucidate the role of the B. pseudomallei cycle-inhibiting factor (Cif) in neuronal cell invasion and pathogenesis.

Main Methods:

  • Infection of human neuronal SH-Sy5y cells with B. pseudomallei strains.
  • Construction and analysis of a B. pseudomallei cif deletion mutant.
  • Assessment of bacterial invasion, intracellular replication, actin-tail formation, and multinucleated giant cell formation.

Main Results:

  • All tested B. pseudomallei strains invaded SH-Sy5y cells, replicated intracellularly, formed actin tails, and induced multinucleated giant cells.
  • A cif deletion mutant showed significantly reduced invasion capabilities in SH-Sy5y cells.
  • Complementation of the cif gene restored the invasion phenotype of the mutant.

Conclusions:

  • The virulence factor Cif plays a critical role in B. pseudomallei invasion of human neuronal cells.
  • These findings advance the understanding of B. pseudomallei pathogenesis in neurological melioidosis.
  • Identifying Cif's function may lead to novel therapeutic strategies for melioidosis.

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