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

Content Provider	Springer Nature : BioMed Central
Author	Hoare, Alexander Timms, Peter Bavoil, Patrik M Wilson, David P
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.
Related Links	https://bmcmicrobiol.biomedcentral.com/counter/pdf/10.1186/1471-2180-8-5.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	14712180
DOI	10.1186/1471-2180-8-5
Journal	BMC Microbiology
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2008-01-09
Access Restriction	Open
Subject Keyword	Microbiology Biological Microscopy Mycology Parasitology Virology Life Sciences Persistent Infection Chlamydial Infection Elementary Body Needle Length Inclusion Membrane
Content Type	Text
Resource Type	Article
Subject	Microbiology Microbiology (medical)
Journal Impact Factor	4/2023
5-Year Journal Impact Factor	4.6/2023

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