Article

Protein expression profiles of Chlamydia pneumoniae in models of persistence versus those of heat shock response

Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, United States
Infection and Immunity (Impact Factor: 4.16). 08/2006; 74(7):3853-63. DOI: 10.1128/IAI.02104-05
Source: PubMed

ABSTRACT Chlamydia pneumoniae is an obligate intracellular pathogen that causes both acute and chronic human disease. Several in vitro models of chlamydial persistence have been established to mimic chlamydial persistence in vivo. We determined the expression patterns of 52 C. pneumoniae proteins, representing nine functional subgroups, from the gamma interferon (IFN-gamma) treatment (primarily tryptophan limitation) and iron limitation (IL) models of persistence compared to those following heat shock (HS) at 42 degrees C. Protein expression patterns of C. pneumoniae persistence indicates a strong stress component, as evidenced by the upregulation of proteins involved in protein folding, assembly, and modification. However, it is clearly more than just a stress response. In IFN persistence, but not IL or HS, amino acid and/or nucleotide biosynthesis proteins were found to be significantly upregulated. In contrast, proteins involved in the biosynthesis of cofactors, cellular processes, energy metabolism, transcription, and translation showed an increased in expression in only the IL model of persistence. These data represent the most extensive protein expression study of C. pneumoniae comparing the chlamydial heat shock stress response to two models of persistence and identifying the common and unique protein level responses during persistence.

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    • "This function is also supported by our data to date for Chlamydia HtrA (Huston et al., 2008), and it is likely that this extracytoplasmic protein protection role is particularly critical during the chlamydial penicillin persistence model. Previously, we and others have reported that CtHtrA is highly expressed during penicillin persistence lab models and down regulated during IFNγ persistence (Belland et al., 2003; Mukhopadhyay et al., 2006; Huston et al., 2008). Therefore, in this project we aimed to test the hypothesis that CtHtrA is essential during penicillin persistence using the CtHtrA inhibitor JO146. "
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    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.
    Frontiers in Cellular and Infection Microbiology 12/2013; 3:100. DOI:10.3389/fcimb.2013.00100 · 2.62 Impact Factor
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    • "The proteins associated with persistent infection could be useful as biomarkers for the diagnosis, as therapeutic targets, and ultimately as responseto-therapy markers. However, the initial studies in this area also failed to reveal a common profile between different models and different chlamydial species (Mukhopadhyay et al., 2006). Upon exposure to IFN-γ, the presence of aberrant C. trachomatis forms was associated with down-regulation of the outer membrane proteins (OmpA, OmpB) in cell culture, while the expression of chlamydial GroEL was unaltered (Beatty et al., 1993). "
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    ABSTRACT: Diagnostic assays for persistent chlamydial infection are much needed to conduct high-quality, large-scale studies investigating the persistent state in vivo, its disease associations and the response to therapy. Yet in most studies the distinction between acute and persistent infection is based on the interpretation of the data obtained by the assays developed to diagnose acute infections or on complex assays available for research only and/or difficult to establish for clinical use. Novel biomarkers for detection of persistent chlamydial infection are urgently needed. Chlamydial whole genome proteome arrays are now available and they can identify chlamydial antigens that are differentially expressed between acute infection and persistent infection. Utilizing these data will lead to the development of novel diagnostic assays. Carefully selected specimens from well-studied patient populations are clearly needed in the process of translating the proteomic data into assays useful for clinical practice. Before such antigens are identified and validated assays become available, we face a challenge of deciding whether the persistent infection truly induced appearance of the proposed marker or do we just base our diagnosis of persistent infection on the presence of the suggested markers. Consequently, we must bear this in mind when interpreting the available data.
    Frontiers in Cellular and Infection Microbiology 12/2013; 3:99. DOI:10.3389/fcimb.2013.00099 · 2.62 Impact Factor
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    • "modulation of host protein synthesis results in pleiotropic effects that likely influence chlamydial growth via means independent of iron starvation. Others have eliminated this need for cyclohexamide through the use of long-term DFO pre-treatment protocols in order to deplete host cells of intracellular iron stores prior to chlamydial invasion (Al-Younes et al., 2001; Peters et al., 2005; Mukhopadhyay et al., 2006; Dill et al., 2009; Timms et al., 2009). While the effects of this protocol could presumably be attributed solely to iron-deprivation, it is tedious and requires the infection of a compromised host cell population. "
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    ABSTRACT: Iron is an essential cofactor in a number of critical biochemical reactions, and as such, its acquisition, storage, and metabolism is highly regulated in most organisms. The obligate intracellular bacterium, Chlamydia trachomatis experiences a developmental arrest when iron within the host is depleted. The nature of the iron starvation response in Chlamydia is relatively uncharacterized because of the likely inefficient method of iron depletion, which currently relies on the compound deferoxamine mesylate (DFO). Inefficient induction of the iron starvation response precludes the identification of iron-regulated genes. This report evaluated DFO with another iron chelator, 2,2'-bipyridyl (Bpdl) and presented a systematic comparison of the two across a range of criteria. We demonstrate that the membrane permeable Bpdl was superior to DFO in the inhibition of chlamydia development, the induction of aberrant morphology, and the induction of an iron starvation transcriptional response in both host and bacteria. Furthermore, iron starvation using Bpdl identified the periplasmic iron-binding protein-encoding ytgA gene as iron-responsive. Overall, the data present a compelling argument for the use of Bpdl, rather than DFO, in future iron starvation studies of chlamydia and other intracellular bacteria.
    Frontiers in Microbiology 02/2011; 2:20. DOI:10.3389/fmicb.2011.00020 · 3.94 Impact Factor
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