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Plasmid coding sequence-five influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection

Plasmid coding sequence-five influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection
Plasmid coding sequence-five influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection
The native plasmid of both Chlamydia muridarum and C. trachomatis has been shown to control virulence and infectivity in mice and in lower primates. We have recently described the development of a plasmid-based genetic transformation protocol for Chlamydia trachomatis that for the first time provides a platform for the molecular dissection of the function of the chlamydial plasmid and its individual genes or coding sequences (CDS). In the present study, we transformed a plasmid-free lymphogranuloma venereum isolate of C. trachomatis, serovar L2, with either the original shuttle vector (pGFP::SW2) or a derivative of pGFP::SW2 carrying a deletion of the plasmid CDS5 gene (pCDS5KO). Female mice were inoculated with these strains either intravaginally or transcervically. We found that transformation of the plasmid-free isolate with the intact pGFP::SW2 vector significantly enhanced infectivity and induction of host inflammatory responses when compared to the plasmid-free parental isolate. Transformation with pCDS5KO resulted in infection courses and inflammatory responses not significantly different from those observed in mice infected with the plasmid-free isolate. These results indicate a critical role of plasmid CDS5 in in vivo fitness and in induction of inflammatory responses. To our knowledge, these are the first in vivo observations ascribing infectivity and virulence to a specific plasmid gene
0019-9567
3341-3349
Ramsey, K.H.
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Schripsema, J.H.
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Smith, B.J.
7edb865a-faca-4bd5-9f94-b08aacfbf587
Wang, Y.
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Jham, B.C.
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O'Hagan, K.P.
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Thomson, N.R.
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Murthy, A.K.
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Skilton, R.J.
b02d4f32-609c-4074-b616-ec819b018dbe
Chu, P.
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Clarke, I.N.
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Ramsey, K.H.
eec8a828-a647-4d53-8d60-e7b9b0db55ef
Schripsema, J.H.
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Smith, B.J.
7edb865a-faca-4bd5-9f94-b08aacfbf587
Wang, Y.
23c775f0-3cac-44d5-9e16-2098959c493b
Jham, B.C.
f85e0fdb-a455-4a76-85be-da38aa978218
O'Hagan, K.P.
10a65df9-e1f4-423c-a559-fbbfbcaa2e1e
Thomson, N.R.
2ab67a93-2afc-4a98-b1e4-8d539b92b351
Murthy, A.K.
b5bf7f02-c28f-4000-8e2e-fd1fd6939ae2
Skilton, R.J.
b02d4f32-609c-4074-b616-ec819b018dbe
Chu, P.
328d86ef-a461-4144-a18d-d7c2e163a652
Clarke, I.N.
ff6c9324-3547-4039-bb2c-10c0b3327a8b

Ramsey, K.H., Schripsema, J.H., Smith, B.J., Wang, Y., Jham, B.C., O'Hagan, K.P., Thomson, N.R., Murthy, A.K., Skilton, R.J., Chu, P. and Clarke, I.N. (2014) Plasmid coding sequence-five influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection. Infection and Immunity, 82 (8), 3341-3349. (doi:10.1128/IAI.01795-14). (PMID:24866804)

Record type: Article

Abstract

The native plasmid of both Chlamydia muridarum and C. trachomatis has been shown to control virulence and infectivity in mice and in lower primates. We have recently described the development of a plasmid-based genetic transformation protocol for Chlamydia trachomatis that for the first time provides a platform for the molecular dissection of the function of the chlamydial plasmid and its individual genes or coding sequences (CDS). In the present study, we transformed a plasmid-free lymphogranuloma venereum isolate of C. trachomatis, serovar L2, with either the original shuttle vector (pGFP::SW2) or a derivative of pGFP::SW2 carrying a deletion of the plasmid CDS5 gene (pCDS5KO). Female mice were inoculated with these strains either intravaginally or transcervically. We found that transformation of the plasmid-free isolate with the intact pGFP::SW2 vector significantly enhanced infectivity and induction of host inflammatory responses when compared to the plasmid-free parental isolate. Transformation with pCDS5KO resulted in infection courses and inflammatory responses not significantly different from those observed in mice infected with the plasmid-free isolate. These results indicate a critical role of plasmid CDS5 in in vivo fitness and in induction of inflammatory responses. To our knowledge, these are the first in vivo observations ascribing infectivity and virulence to a specific plasmid gene

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e-pub ahead of print date: 27 May 2014
Published date: August 2014
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 365678
URI: https://eprints.soton.ac.uk/id/eprint/365678
ISSN: 0019-9567
PURE UUID: a51cb293-5009-49e3-9240-1f06768cadf4
ORCID for I.N. Clarke: ORCID iD orcid.org/0000-0002-4938-1620

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Date deposited: 13 Jun 2014 15:39
Last modified: 15 Aug 2019 00:58

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Contributors

Author: K.H. Ramsey
Author: J.H. Schripsema
Author: B.J. Smith
Author: Y. Wang
Author: B.C. Jham
Author: K.P. O'Hagan
Author: N.R. Thomson
Author: A.K. Murthy
Author: R.J. Skilton
Author: P. Chu
Author: I.N. Clarke ORCID iD

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