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.
Highlights
Chlamydia trachomatis is a unique obligate intracellular bacterial pathogen
JO146 ADDITION TO C. trachomatis HEp-2 CULTURES DURING PENICILLIN PERSISTENCE RESULTS IN A REDUCED VIABLE YIELD Due to the bi-phasic nature of the chlamydial developmental cycle it is not possible to measure the immediate impact on viability during the replicative phase of growth
We first wanted to monitor the impact of JO146 addition during persistence when aberrant bodies are present, for this experiment we added JO146 during persistence at 16 h PI and one set of cultures were harvested to measure viability and fixed and examined by confocal microscopy at 44 h PI
Summary
Chlamydia trachomatis is a unique obligate intracellular bacterial pathogen. The organism is typified by a bi-phasic developmental cycle. Persistent Chlamydia ( called aberrant bodies), are morphologically distinct from the active replicating form with only a few cells visible per inclusion which are much larger size) (Moulder, 1993; Byrne et al, 2001; Hogan et al, 2004; Wyrick, 2010). This ability to become persistent is thought to provide the organism with a survival mechanism to avoid any conditions where they would be unable to survive. Persistence is induced by immune pressure, amino acid deprivation, penicillin, iron limitation, or the presence of other intracellular pathogens (Beatty et al, 1993, 1994a,b; Coles et al, 1993; Byrne et al, 2001; Wyrick and Knight, 2004; CDC, 2005–2009/2010; Deka et al, 2006)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
