Eukaryotic pathways targeted by the type III secretion system effector protein, BipC, involved in the intracellular lifecycle of Burkholderia pseudomallei

Abstract

Burkholderia pseudomallei, the etiological agent for melioidosis, is known to secrete a type III secretion system (TTSS) protein into the host’s internal milieu. One of the TTSS effector protein, BipC, has been shown to play an important role in the B. pseudomallei pathogenesis. To identify the host response profile that was directly or indirectly regulated by this protein, genome-wide transcriptome approach was used to examine the gene expression profiles of infected mice. The transcriptome analysis of the liver and spleen revealed that a total of approximately 1,000 genes were transcriptionally affected by BipC. Genes involved in bacterial invasion, regulation of actin cytoskeleton, and MAPK signalling pathway were over-expressed and may be specifically regulated by BipC in vivo. These results suggest that BipC mainly targets pathways related to the cellular processes which could modulate the cellular trafficking processes. The host transcriptional response exhibited remarkable differences with and without the presence of the BipC protein. Overall, the detailed picture of this study provides new insights that BipC may have evolved to efficiently manipulate host-cell pathways which is crucial in the intracellular lifecycle of B. pseudomallei.

Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis

“…Among these, TLRs are known to recognize B. pseudomallei LPS and initiate inflammation [33][34][35][36] and acute septic melioidosis patients had increased expression of many TLRs in leukocytes [34]. The activation of MAPK signaling and Th17 pathway in melioidosis patients have also been demonstrated in previous studies [37][38][39] [40]. Multiple signaling pathways were downregulated in severe melioidosis suggesting that prolonged bacterial persistence exacerbates inflammatory responses that may lead to immune exhaustion, immune suppression, and poor outcome of the disease.…”

Melioidosis in Malaysia: Incidence, Clinical Challenges, and Advances in Understanding Pathogenesis

“…This study was extended to further evaluate the role of the cell invasion protein, BipC, in pathogenesis of B. pseudomallei . BipC, an immunoreactive protein, is involved in actin binding to facilitate internalization of B. pseudomallei into host cells, as a bipC mutant was impaired in adherence, invasion, and intracellular survival in epithelial cells, and BipC protein is required for full virulence in a murine model of melioidosis [ 78 , 79 ]. Recently, Vadivelu et al [ 80 ] showed that B. pseudomallei localized within the nuclear compartment of host cells, suggesting that the nucleus may play a role as an occult or transient niche for persistence of intracellular pathogens, potentially leading to recurrent episodes or recrudescence of infection.…”

Upregulation of Immune Process-Associated Genes in RAW264.7 Macrophage Cells in Response toBurkholderia pseudomalleiInfection

“…To identify host responses that are directly or indirectly regulated by Burkholderia invasion protein C (BipC), transcriptomic analysis of the liver and spleen tissues of infected mice was performed. The results demonstrated that BipC mainly targets cellular processes related pathways, which can modulate cellular trafficking [ 13 ].…”