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.
Abstract:
Burkholderia pseudomallei is a pathogenic bacterium that causes human melioidosis, which is associated with a high mortality rate. However, the underlying mechanisms of B. pseudomallei pathogenesis are largely unknown. In this study, we examined the infection of human neuronal SH-Sy5y cells by several clinically relevant B. pseudomallei strains. We found that all tested B. pseudomallei strains can invade SH-Sy5y cells, undergo intracellular replication, cause actin-tail formation, and form multinucleated giant cells. Additionally, a deletion mutant of B. pseudomallei cycle-inhibiting factor (cif) was constructed that exhibited reduced invasion in SH-Sy5y cells. Complementation of cif restored invasion of the B. pseudomallei cif-deleted mutant. Our findings enhance understanding of B. pseudomallei pathogenicity in terms of the virulence factor Cif and demonstrate the function of Cif in neurological melioidosis. This may eventually lead to the discovery of novel targets for treatment and a strategy to control the disease.
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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