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Mathematical Model for Length Control by the Timing of Substrate Switching in the Type III Secretion System
Nariya, Maulik K. Israeli, Johnny Shi, Jack J. Deeds, Eric J.
Nariya, Maulik K.
Israeli, Johnny
Shi, Jack J.
Deeds, Eric J.
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Abstract
Type III Secretion Systems (T3SS) are complex bacterial structures that provide gram-negative pathogens with a unique virulence mechanism whereby they grow a needle-like structure in order to inject bacterial effector proteins into the cytoplasm of a host cell. Numerous experiments have been performed to understand the structural details of this nanomachine during the past decade. Despite the concerted efforts of molecular and structural biologists, several crucial aspects of the assembly of this structure, such as the regulation of the length of the needle itself, remain unclear. In this work, we used a combination of mathematical and computational techniques to better understand length control based on the timing of substrate switching, which is a possible mechanism for how bacteria ensure that the T3SS needles are neither too short nor too long. In particular, we predicted the form of the needle length distribution based on this mechanism, and found excellent agreement with available experimental data from Salmonella typhimurium with only a single free parameter. Although our findings provide preliminary evidence in support of the substrate switching model, they also make a set of quantitative predictions that, if tested experimentally, would assist in efforts to unambiguously characterize the regulatory mechanisms that control the growth of this crucial virulence factor.
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A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.
Date
2016-04
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Public Library of Science
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Nariya, M. K., Israeli, J., Shi, J. J., & Deeds, E. J. (2016). Mathematical Model for Length Control by the Timing of Substrate Switching in the Type III Secretion System. PLoS Computational Biology, 12(4), e1004851. http://doi.org/10.1371/journal.pcbi.1004851