From Assembly to Secretion: Deciphering the role of dynamic components in the Type III Secretion System
Loading...
Files
Date
relationships.isAuthorOf
Publisher
Philipps-Universität Marburg
item.page.supervisor-of-thesis
Abstract
Many Gram-negative bacterial pathogens possess a conserved virulence factor called the Type III Secretion System (T3SS), often referred to as the injectisome, which resembles a syringe with an extracellular needle. The T3SS enables these pathogens to inject proteins, known as effectors, directly into the cytoplasm of host eukaryotic cells, manipulating their cellular processes to promote bacterial survival and facilitate infection. Over the past few decades, significant progress has been made in deciphering the precise structure of this nanomachine, providing deeper insights into its function. However, the T3SS and other protein complexes are far from the stable, uniformly defined complexes that these structural studies might suggest. Recent research has revealed that the T3SS undergoes a continuous dynamic protein exchange of its cytosolic components, which correlates with T3SS function, although the direct causal relationship remains unclear.
At the beginning of my thesis, it was not known whether other parts of the T3SS exhibit dynamic behavior and what the biological significance of such dynamics might be. In my PhD research, I studied the dynamic nature of three key parts of the T3SS: the pilotin SctG that assists the formation of the outer membrane ring of the T3SS, the cytosolic components that order the export of the various T3SS substrates, and the structural inner membrane ring component SctD. In the thesis, I show that the dynamics in the T3SS are not limited to the cytosolic components but also extend to include both the lipoprotein SctG in the outer membrane and the integral inner membrane protein SctD. Specifically, SctG transiently associates with the T3SS and primarily diffuses within the membrane. In contrast, the SctD proteins bound to the T3SS undergo subunit exchange with a membrane-associated pool, like what was observed with the cytosolic components, though their exchange occurs with a cytoplasmic pool.
I further found that the dynamic behavior of SctG and SctD plays a crucial role during the assembly process of the T3SS. The diffusion of SctG within the membrane enables to determine the location and promote the assembly of the T3SS. In the following steps of T3SS assembly, the subunit exchange of SctD facilitates the integration of the export apparatus into the inner membrane ring structure that SctD forms. The findings in my thesis further show that once the T3SS is assembled, the dynamic nature of SctG, SctD, and the cytosolic components also significantly contribute to the secretion of the different T3SS substrates. Notably, the absence of SctG strongly disrupts the export of early substrates, like needle components, but has little effect on the late substrates, including effectors. We propose that SctG dissociation from the T3SS triggers a shift in export specificity between these substrate groups. Simultaneously, the development of an SctD mutant, whose exchange can be controlled by crosslinking, revealed reduced effector secretion when exchange was restricted, suggesting that SctD exchange facilitates secretion. Finally, my thesis demonstrates that the cytosolic components SctQ and SctL directly bind to effector/chaperone complexes in the cytoplasm. This interaction supports us to propose a shuttling mechanism that transports effectors from the cytoplasm to the membrane-anchored T3SS, thereby promoting their secretion. Ultimately, our findings presented in this thesis provide significant insight into the dynamic nature of the T3SS, highlighting its crucial role in ensuring proper assembly and function for the injection of virulent effectors.
.
Review
Metadata
Contributors
Supervisor:
Dates
Created: 2024Issued: 2025-11-26Updated: 2025-05-15
Faculty
Fachbereich Biologie
Language
eng
Data types
DoctoralThesis
Keywords
Dynamic componentsAsemblySecretionDynamische KomponentenZusammenbauSekretion
DFG-subjects
Type III Secretion SystemT3SS
DDC-Numbers
570
show more
Brianceau, Corentin: From Assembly to Secretion: Deciphering the role of dynamic components in the Type III Secretion System. : Philipps-Universität Marburg 2025-11-26. DOI: https://doi.org/10.17192/z2024.0508.