Development of a lambda Red based system for gene deletion in Chlamydia.

The ability to efficiently target loci in the Chlamydia trachomatis genome for deletion remains a desirable goal in the field and new strategies need to be developed and refined. Here we describe the development and application of a lambda red recombineering system for Chlamydia. Using a non-replica...

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Main Authors: Yibing Wang, Robert Suchland, Amy Hua, Steven Carrell, Daniel Rockey, Kevin Hybiske
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0311630
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author Yibing Wang
Robert Suchland
Amy Hua
Steven Carrell
Daniel Rockey
Kevin Hybiske
author_facet Yibing Wang
Robert Suchland
Amy Hua
Steven Carrell
Daniel Rockey
Kevin Hybiske
author_sort Yibing Wang
collection DOAJ
description The ability to efficiently target loci in the Chlamydia trachomatis genome for deletion remains a desirable goal in the field and new strategies need to be developed and refined. Here we describe the development and application of a lambda red recombineering system for Chlamydia. Using a non-replicative plasmid encoding key lambda Red components and targeting sequences, we demonstrate the efficient deletion of numerous gene targets in the model chlamydial strains C. trachomatis L2/434 and C. muridarum. For initial development of the system, we targeted the incA gene of C. trachomatis for deletion. Deletion mutants containing a chloramphenicol resistance marker were recovered within 3 rounds of selection, or 2 rounds of passaging, in McCoy cells and the resulting clones (CTΔincA) were verified by PCR-based genotyping and whole genome sequencing. Phenotypic assessment of host cells infected with CTΔincA was performed by immunofluorescence microscopy and confirmed the lack of IncA expression and the uniform presence of nonfusogenic vacuoles (inclusions) across CTΔincA-infected monolayers. To explore the utility of this system, we deleted 5 additional candidate virulence factors in C. trachomatis and C. muridarum, including deletions of single and multiple genes. We expect lambda Red recombineering to offer a powerful new strategy for making gene deletion and/or replacement mutants in Chlamydia.
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spelling doaj-art-3cfbad8539a347429c01a29500bdf45d2025-08-20T03:13:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011911e031163010.1371/journal.pone.0311630Development of a lambda Red based system for gene deletion in Chlamydia.Yibing WangRobert SuchlandAmy HuaSteven CarrellDaniel RockeyKevin HybiskeThe ability to efficiently target loci in the Chlamydia trachomatis genome for deletion remains a desirable goal in the field and new strategies need to be developed and refined. Here we describe the development and application of a lambda red recombineering system for Chlamydia. Using a non-replicative plasmid encoding key lambda Red components and targeting sequences, we demonstrate the efficient deletion of numerous gene targets in the model chlamydial strains C. trachomatis L2/434 and C. muridarum. For initial development of the system, we targeted the incA gene of C. trachomatis for deletion. Deletion mutants containing a chloramphenicol resistance marker were recovered within 3 rounds of selection, or 2 rounds of passaging, in McCoy cells and the resulting clones (CTΔincA) were verified by PCR-based genotyping and whole genome sequencing. Phenotypic assessment of host cells infected with CTΔincA was performed by immunofluorescence microscopy and confirmed the lack of IncA expression and the uniform presence of nonfusogenic vacuoles (inclusions) across CTΔincA-infected monolayers. To explore the utility of this system, we deleted 5 additional candidate virulence factors in C. trachomatis and C. muridarum, including deletions of single and multiple genes. We expect lambda Red recombineering to offer a powerful new strategy for making gene deletion and/or replacement mutants in Chlamydia.https://doi.org/10.1371/journal.pone.0311630
spellingShingle Yibing Wang
Robert Suchland
Amy Hua
Steven Carrell
Daniel Rockey
Kevin Hybiske
Development of a lambda Red based system for gene deletion in Chlamydia.
PLoS ONE
title Development of a lambda Red based system for gene deletion in Chlamydia.
title_full Development of a lambda Red based system for gene deletion in Chlamydia.
title_fullStr Development of a lambda Red based system for gene deletion in Chlamydia.
title_full_unstemmed Development of a lambda Red based system for gene deletion in Chlamydia.
title_short Development of a lambda Red based system for gene deletion in Chlamydia.
title_sort development of a lambda red based system for gene deletion in chlamydia
url https://doi.org/10.1371/journal.pone.0311630
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