title: Mathematical Model for Length Control by the Timing of Substrate Switching in the Type III Secretion System.
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.
authors.affiliation: Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas, United States of America.
authors.forename: Maulik K
authors.initials: MK
authors.lastname: Nariya
authors.affiliation: Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas, United States of America.
authors.forename: Johnny
authors.initials: J
authors.lastname: Israeli
authors.affiliation: Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas, United States of America.
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Shi
authors.affiliation: Center for Computational Biology, University of Kansas, Lawrence, Kansas, United States of America.|Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, United States of America.|Sante Fe Institute, Santa Fe, New Mexico, United States of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Deeds
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology; D019295:Computational Biology; D003198:Computer Simulation; D054884:Host-Pathogen Interactions / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D059748:Proteolysis; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology*; D013269:Stochastic Processes; D000069296:Type III Secretion Systems / Q000737:chemistry / Q000502:physiology*; D014774:Virulence / Q000502:physiology; D037521:Virulence Factors / Q000737:chemistry / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D000069296:Type III Secretion Systems; D037521:Virulence Factors