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Spatial constraints within the chlamydial host cell inclusion predict interrupted development and persistence

Hoare, Alexander, Timms, Peter, Bavoil, Patrik M., & Wilson, David P. (2008) Spatial constraints within the chlamydial host cell inclusion predict interrupted development and persistence. BMC Microbiology, 8(5).

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Abstract

BACKGROUND: The chlamydial developmental cycle involves the alternation between the metabolically inert elementary body (EB) and the replicating reticulate body (RB). The triggers that mediate the interchange between these particle types are unknown and yet this is crucial for understanding basic Chlamydia biology. PRESENTATION OF THE HYPOTHESIS: We have proposed a hypothesis to explain key chlamydial developmental events whereby RBs are replicating strictly whilst in contact with the host cell membrane-derived inclusion via type three secretion (T3S) injectisomes. As the inclusion expands, the contact between each RB and the inclusion membrane decreases, eventually reaching a threshold, beyond which T3S is inactivated upon detachment and this is the signal for RB-to-EB differentiation. TESTING THE HYPOTHESIS: We explore this hypothesis through the development of a detailed mathematical model. The model uses knowledge and data of the biological system wherever available and simulates the chlamydial developmental cycle under the assumptions of the hypothesis in order to predict various outcomes and implications under a number of scenarios. IMPLICATIONS OF THE HYPOTHESIS: We show that the concept of in vitro persistent infection is not only consistent with the hypothesis but in fact an implication of it. We show that increasing the RB radius, and/or the maximum length of T3S needles mediating contact between RBs and the inclusion membrane, and/or the number of inclusions per infected cell, will contribute to the development of persistent infection. The RB radius is the most important determinant of whether persistent infection would ensue, and subsequently, the magnitude of the EB yield. We determine relationships between the length of the T3S needle and the RB radius within an inclusion, and between the RB radius and the number of inclusions per host cell to predict whether persistent infection or normal development would occur within a host cell. These results are all testable experimentally and could lead to significantly greater understanding of one of the most crucial steps in chlamydial development.

Impact and interest:

15 citations in Scopus
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15 citations in Web of Science®

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40 since deposited on 10 Jun 2008
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ID Code: 13704
Item Type: Journal Article
Keywords: infectious diseases, cells and tissue, ihbi, Bacterial proteins, metabolism, Chlamydia, Inclusion Bodies
DOI: 10.1186/1471-2180-8-5
ISSN: 1471-2180
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Microbiology not elsewhere classified (060599)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Metabolism (060104)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Infectious Agents (060502)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Bacteriology (060501)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2008 (The authors)
Copyright Statement: Copyright 2008 Hoare et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 10 Jun 2008
Last Modified: 29 Feb 2012 23:49

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