Chlamydia trachomatis responds to heat shock, penicillin induced persistence, and IFN-gamma persistence by altering levels of the extracytoplasmic stress response protease HtrA

Institute of Health and Biomedical Innovation, 60 Musk Ave, Queensland University of Technology, Kelvin Grove, QLD, 4059, Australia.
BMC Microbiology (Impact Factor: 2.73). 02/2008; 8(1):190. DOI: 10.1186/1471-2180-8-190
Source: PubMed


Chlamydia trachomatis, an obligate intracellular human pathogen, is the most prevalent bacterial sexually transmitted infection worldwide and a leading cause of preventable blindness. HtrA is a virulence and stress response periplasmic serine protease and molecular chaperone found in many bacteria. Recombinant purified C. trachomatis HtrA has been previously shown to have both activities. This investigation examined the physiological role of Chlamydia trachomatis HtrA.
The Chlamydia trachomatis htrA gene complemented the lethal high temperature phenotype of Escherichia coli htrA- (>42 degrees C). HtrA levels were detected to increase by western blot and immunofluorescence during Chlamydia heat shock experiments. Confocal laser scanning microscopy revealed a likely periplasmic localisation of HtrA. During penicillin induced persistence of Chlamydia trachomatis, HtrA levels (as a ratio of LPS) were initially less than control acute cultures (20 h post infection) but increased to more than acute cultures at 44 h post infection. This was unlike IFN-gamma persistence where lower levels of HtrA were observed, suggesting Chlamydia trachomatis IFN-gamma persistence does not involve a broad stress response.
The heterologous heat shock protection for Escherichia coli, and increased HtrA during cell wall disruption via penicillin and heat shock, indicates an important role for HtrA during high protein stress conditions for Chlamydia trachomatis.

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    • "Our group identified a serine protease inhibitor, JO146, against C. trachomatis High Temperature Requirement A (CtHtrA) [8] [9] [10] [11]. JO146 was found to be lethal to C. trachomatis D when added at the mid-replicative stage of the chlamydial developmental cycle [8]. "
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    ABSTRACT: The present study aimed to establish if a previously identified Chlamydia trachomatis HtrA (CtHtrA) inhibitor, JO146, is effective against currently circulating clinical isolates to validate if CtHtrA is a clinically relevant target for future therapeutic development. Inhibition of CtHtrA during the middle of the chlamydial replicative cycle until the completion of the cycle resulted in loss of infectious progeny for six unique clinical isolates representing different serovars. This supports the potential for CtHtrA to be a clinically relevant target for development of new therapeutics and suggests the importance of further investigation of JO146 as a lead compound.
    Microbes and Infection 09/2015; DOI:10.1016/j.micinf.2015.09.004 · 2.86 Impact Factor
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    • "Activity-based probe binding was conducted on cultures from T25 flasks at different time points, while the competitive binding assays were conducted on cultures from T80 flasks harvested at 22 h PI. Western blots for CtHtrA and MOMP were conducted as previously described (Huston et al., 2008). "
    Dataset: chlamydia

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    • "MV formation may offer a means to remove stress caused by the accumulated “toxic” waste or unfolded proteins. Chlamydial HtrA, a key player in envelope stress response (Huston et al., 2007, 2008; Zhong, 2011), is likely to play a role in controlling the formation of MVs, as is observed in other bacteria (McBroom et al., 2006). Given the strong capacity of chlamydial exploitation of host cellular machinery, MV cargo delivery may partially depend on a yet to be defined host trafficking pathway. "
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    ABSTRACT: Bacteria have evolved specific adaptive responses to cope with changing environments. These adaptations include stress response phenotypes with dynamic modifications of the bacterial cell envelope and generation of membrane vesicles (MVs). The obligate intracellular bacterium, Chlamydia trachomatis, typically has a biphasic lifestyle, but can enter into an altered growth state typified by morphologically aberrant chlamydial forms, termed persistent growth forms, when induced by stress in vitro. How C. trachomatis can adapt to a persistent growth state in host epithelial cells in vivo is not well understood, but is an important question, since it extends the host-bacterial relationship in vitro and has thus been indicated as a survival mechanism in chronic chlamydial infections. Here, we review recent findings on the mechanistic aspects of bacterial adaptation to stress with a focus on how C. trachomatis remodels its envelope, produces MVs, and the potential important consequences of MV production with respect to host-pathogen interactions. Emerging data suggest that the generation of MVs may be an important mechanism for C. trachomatis intracellular survival of stress, and thus may aid in the establishment of a chronic infection in human genital epithelial cells.
    Frontiers in Cellular and Infection Microbiology 06/2014; 4:73. DOI:10.3389/fcimb.2014.00073 · 3.72 Impact Factor
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