The protease inhibitor JO146 demonstrates a critical role for CtHtrA for Chlamydia trachomatis reversion from penicillin persistence

Ong, VA; Marsh, JW; Lawrence, A; Allan, JA; Timms, P; Huston, WM

The protease inhibitor JO146 demonstrates a critical role for CtHtrA for Chlamydia trachomatis reversion from penicillin persistence

Ong, VA Marsh, JW

Lawrence, A Allan, JA Timms, P Huston, WM

Permalink

Publication Type:: Journal Article
Citation:: Frontiers in Cellular and Infection Microbiology, 2013, 3 (DEC)
Issue Date:: 2013-12-01

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Published VersionAdobe PDF (2.2 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Ong, VA	en_US
dc.contributor.author	Marsh, JW https://orcid.org/0000-0003-4681-1012	en_US
dc.contributor.author	Lawrence, A	en_US
dc.contributor.author	Allan, JA	en_US
dc.contributor.author	Timms, P	en_US
dc.contributor.author	Huston, WM https://orcid.org/0000-0002-0879-1287	en_US
dc.date.available	2013-12-03	en_US
dc.date.issued	2013-12-01	en_US
dc.identifier.citation	Frontiers in Cellular and Infection Microbiology, 2013, 3 (DEC)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/36791
dc.description.abstract	The Chlamydia trachomatis serine protease HtrA (CtHtrA) has recently been demonstrated to be essential during the replicative phase of the chlamydial developmental cycle. A chemical inhibition strategy (serine protease inhibitor JO146) was used to demonstrate this essential role and it was found that the chlamydial inclusions diminish in size and are lost from the cell after CtHtrA inhibition without formation of viable elementary bodies. The inhibitor (JO146) was used in this study to investigate the role of CtHtrA for penicillin persistence and heat stress conditions for Chlamydia trachomatis. JO146 addition during penicillin persistence resulted in only minor reductions (~1 log) in the final viable infectious yield after persistent Chlamydia were reverted from persistence. However, JO146 treatment during the reversion and recovery from penicillin persistence was completely lethal for Chlamydia trachomatis. JO146 was completely lethal when added either during heat stress conditions, or during the recovery from heat stress conditions. These data together indicate that CtHtrA has essential roles during some stress environments (heat shock), recovery from stress environments (heat shock and penicillin persistence), as well as the previously characterized essential role during the replicative phase of the chlamydial developmental cycle. Thus, CtHtrA is an essential protease with both replicative phase and stress condition functions for Chlamydia trachomatis. © 2013 Ong, Marsh, Lawrence, Allan, Timms and Huston.	en_US
dc.relation.ispartof	Frontiers in Cellular and Infection Microbiology	en_US
dc.relation.isbasedon	10.3389/fcimb.2013.00100	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Chlamydia trachomatis	en_US
dc.subject.mesh	Penicillins	en_US
dc.subject.mesh	Serine Endopeptidases	en_US
dc.subject.mesh	Protease Inhibitors	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Penicillin Resistance	en_US
dc.subject.mesh	Microbial Viability	en_US
dc.subject.mesh	Hep G2 Cells	en_US
dc.title	The protease inhibitor JO146 demonstrates a critical role for CtHtrA for Chlamydia trachomatis reversion from penicillin persistence	en_US
dc.type	Journal Article
utslib.citation.volume	DEC	en_US
utslib.citation.volume	3	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	open_access
pubs.issue	DEC	en_US
pubs.publication-status	Published	en_US
pubs.volume	3	en_US

Abstract:

The Chlamydia trachomatis serine protease HtrA (CtHtrA) has recently been demonstrated to be essential during the replicative phase of the chlamydial developmental cycle. A chemical inhibition strategy (serine protease inhibitor JO146) was used to demonstrate this essential role and it was found that the chlamydial inclusions diminish in size and are lost from the cell after CtHtrA inhibition without formation of viable elementary bodies. The inhibitor (JO146) was used in this study to investigate the role of CtHtrA for penicillin persistence and heat stress conditions for Chlamydia trachomatis. JO146 addition during penicillin persistence resulted in only minor reductions (~1 log) in the final viable infectious yield after persistent Chlamydia were reverted from persistence. However, JO146 treatment during the reversion and recovery from penicillin persistence was completely lethal for Chlamydia trachomatis. JO146 was completely lethal when added either during heat stress conditions, or during the recovery from heat stress conditions. These data together indicate that CtHtrA has essential roles during some stress environments (heat shock), recovery from stress environments (heat shock and penicillin persistence), as well as the previously characterized essential role during the replicative phase of the chlamydial developmental cycle. Thus, CtHtrA is an essential protease with both replicative phase and stress condition functions for Chlamydia trachomatis. © 2013 Ong, Marsh, Lawrence, Allan, Timms and Huston.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/36791