Burkholderia pseudomallei BimC Is Required for Actin-Based Motility, Intracellular Survival, and Virulence

• Published in: Frontiers in cellular and infection microbiology Vol. 9; p. 63
• Main Authors: Srinon, Varintip, Chaiwattanarungruengpaisan, Somjit, Korbsrisate, Sunee, Stevens, Joanne M.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.03.2019
• Subjects: actin-based motility; Actins - metabolism; Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; BimA; BimC; Burkholderia pseudomallei; Burkholderia pseudomallei - growth & development; Burkholderia pseudomallei - metabolism; Cell Line; Cellular and Infection Microbiology; Epithelial Cells - microbiology; Gene Deletion; Humans; intracellular survival; Kinesin - genetics; Kinesin - metabolism; Locomotion; Macrophages - microbiology; Mice; multi-nucleated giant cell; Virulence; BimC; actin-based motility; intracellular survival; BimA; virulence; multi-nucleated giant cell; Burkholderia pseudomallei
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2019.00063

The intracellular pathogen , the etiological agent of melioidosis in humans and various animals, is capable of survival and movement within the cytoplasm of host cells by a process known as actin-based motility. The bacterial factor BimA is required for actin-based motility through its direct interaction with actin, and by mediating actin polymerization at a single pole of the bacterium to promote movement both within and between cells. However, little is known about the other bacterial proteins required for this process. Here, we have investigated the role of the gene ( ) which lies immediately upstream of the gene ( ) on the chromosome 2. Conserved amongst all and strains sequenced to date, this gene encodes an iron-binding protein with homology to a group of proteins known as the bacterial autotransporter heptosyltransferase (BAHT) family. We have constructed a deletion mutant and demonstrate that it is defective in intracellular survival in HeLa cells, but not in J774.1 macrophage-like cells. The mutant is defective in cell to cell spread as demonstrated by ablation of plaque formation in HeLa cells, and by the inability to form multi-nucleated giant cells in J774.1 cells. These phenotypes in intracellular survival and cell to cell spread are not due to the loss of expression and polar localization of the BimA protein on the surface of intracellular bacteria, however they do correlate with an inability of the bacteria to recruit and polymerize actin. Furthermore, we also establish a role for in virulence of using a larvae model of infection. Taken together, our findings indicate that BimC plays an important role in intracellular behavior and virulence of this emerging pathogen.