Abstract
Bordetella bronchiseptica is genetically related to B. pertussis and B. parapertussis, which cause respiratory tract infections in humans. These pathogens possess a large number of virulence factors, including the type III secretion system (T3SS), which is required for the delivery of effectors into the host cells. In a previous study, we identified a transcriptional regulator, BspR, that is involved in the regulation of the T3SS-related genes in response to iron-starved conditions. A unique feature of BspR is that this regulator is secreted into the extracellular milieu via the T3SS. To further characterize the role of BspR in extracellular localization, we constructed various truncated derivatives of BspR and investigated their translocation into the host cells using conventional translocation assays. In this study, the effector translocation was evaluated by the T3SS of enteropathogenic E. coli (EPEC), since the exogenous expression of BspR triggers severe repression of the Bordetella T3SS expression. The results of the translocation assays using the EPEC T3SS showed that the N-terminal 150 amino acid (aa) residues of BspR are sufficient for translocation into the host cells in a T3SS-dependent manner. In addition, exogenous expression of BspR in HeLa cells demonstrated that the N-terminal 100 aa residues are involved in the nuclear localization. In contrast, the N-terminal 54 aa residues are sufficient for the extracellular secretion into the bacterial culture supernatant via the EPEC T3SS. Thus, BspR is not only a transcriptional regulator in bacteria cytosol, but also functions as an effector that translocates into the nuclei of infected host cells.
Highlights
The genus Bordetella is a Gram-negative aerobic coccobacilli that is currently subclassified into nine species [1]
To determine whether BspR is translocated into the host cells via the T3SS, plasmids carrying the full length BspR or its truncated derivatives fused with CyaA were constructed and introduced into the B. bronchiseptica S798 ΔbteA ΔcyaA strain, which is deficient in the induction of host cell death by the effector BteA [10] and lacks endogenous CyaA activity (S1 Fig)
We have demonstrated that BspR can be translocated into the host cells via the T3SS using enteropathogenic E. coli (EPEC) as host bacteria (Figs 2 and 3)
Summary
The genus Bordetella is a Gram-negative aerobic coccobacilli that is currently subclassified into nine species [1]. B. bronchiseptica, Bordetella pertussis, and B. parapertussis share a large number of virulence factors, including toxins, adhesins, and components of the type III secretion system (T3SS) [2]. ParapertussisHU are strictly human-adapted pathogens and are the etiological agents of whooping cough (pertussis) in humans. To exert full virulence in the hosts, Bordetella coordinately regulates a number of virulence genes by a two-component signal transduction system, BvgA and BvgS (BvgAS) [5]. The resulting activated BvgA is able to bind to promoter regions, leading to the transcriptional activation of a wide variety of virulence genes (Bvg+ phase) [7]. Bordetella virulence genes are coordinately regulated by the BvgAS system in response to various environmental conditions
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