Detection of Chlamydia trachomatis in Fallopian tube tissue in women with postinfectious tubal infertility

Department of Obstetrics and Gynecology, University of Washington, Seattle 98195.
American Journal of Obstetrics and Gynecology (Impact Factor: 3.97). 08/1994; 171(1):95-101. DOI: 10.1016/S0002-9378(94)70084-2
Source: PubMed

ABSTRACT Biopsy tissues from women with postinfectious tubal infertility were studied for the presence of Chlamydia trachomatis.
Tubal biopsy specimens from 25 women with postinfectious tubal infertility undergoing laparoscopy for repair of fallopian tubes were evaluated by culture, in situ hybridization. Immunocytochemistry, and transmission electron microscopy for the presence of Chlamydia trachomatis. Serum was also tested for Chlamydia trachomatis antibodies.
Chlamydia trachomatis was detected in postinfectious tubal biopsy specimens in three of 25 patients by culture, 12 of 24 by in situ hybridization, 15 of 22 by immunoperoxidase stain, and two of 10 by transmission electron microscopy. Serum antibody against Chlamydia trachomatis was detected in 15 of 21 patients.
Chlamydia trachomatis deoxyribonucleic acid or antigens were detected at a high percentage (19/24 women) in the biopsy tissues of the fimbrial and peritubal adhesions by in situ hybridization or immunoperoxidase stain, suggesting a persistent infection in these women even after antibiotic treatment.

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    • "Of these, varying levels of IFNγ in the endocervix during chlamydial infection in vivo are likely crucial as demonstrated by studies in vitro, in animal models, and in observational studies in humans (Arno et al., 1990; Beatty et al., 1994a; Byrne, 2001; Aiyar et al., 2014; Lewis et al., 2014). The direct involvement of persistent growth forms in pathogenesis in vivo in humans is challenging to prove, but several TEM studies have visualized atypical pleomorphic RBs and aberrant C. trachomatis forms in individuals with chronic infections, in Fallopian tube tissues, and in the synovium of reactive arthritis patients (Patton et al., 1994; Nanagara et al., 1995; Mazzoli et al., 2000; Bragina et al., 2001). Very recently, the Quayle laboratory developed methodology to sample endocervical cells and components of the endocervical environment in C. trachomatis infected women. "
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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 · 2.62 Impact Factor
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    • "This bacterial form is viable but non-cultivable and results in an extended relationship between the pathogen and its host cell (ibid). Compelling, but thus far indirect evidence, for this alternative mode of growth in vivo includes documentation of recurrent disease when re-infection is unlikely, and the detection of chlamydial antigen or nucleic acid in the absence of cultivability (Nagasaki, 1987; Patton et al., 1994; Dean et al., 2000). Classic in vitro studies have shown C. trachomatis has a unique developmental cycle that normally alternates between an infectious elementary body (EB) and a non-infectious reticulate body (RB) (Abdelrahman and Belland, 2005). "
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    ABSTRACT: In vitro models of Chlamydia trachomatis growth have long been studied to predict growth in vivo. Alternative or persistent growth modes in vitro have been shown to occur under the influence of numerous stressors but have not been studied in vivo. Here, we report the development of methods for sampling human infections from the endocervix in a manner that permits a multifaceted analysis of the bacteria, host and the endocervical environment. Our approach permits evaluating total bacterial load, transcriptional patterns, morphology by immunofluorescence and electron microscopy, and levels of cytokines and nutrients in the infection microenvironment. By applying this approach to two pilot patients with disparate infections, we have determined that their contrasting growth patterns correlate with strikingly distinct transcriptional biomarkers, and are associated with differences in local levels of IFNγ. Our multifaceted approach will be useful to dissect infections in the human host and be useful in identifying patients at risk for chronic disease. Importantly, the molecular and morphological analyses described here indicate that persistent growth forms can be isolated from the human endocervix when the infection microenvironment resembles the in vitro model of IFNγ-induced persistence.
    Frontiers in Cellular and Infection Microbiology 06/2014; 4:71. DOI:10.3389/fcimb.2014.00071 · 2.62 Impact Factor
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    • "Continued chlamydial infections and repeat infections with the same serovar are common, despite appropriate antibiotic therapy (Patton et al., 1994; Fortenberry et al., 1999; Dean et al., 2000). Chlamydial AB have been observed in samples from patients and infected animals (Nanagara et al., 1995; Skowasch et al., 2003; Pospischil et al., 2009; Rank et al., 2011). "
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    ABSTRACT: Chlamydia trachomatis, the most common bacterial sexually transmitted disease agent worldwide, enters a viable, non-dividing and non-infectious state (historically termed persistence and more recently referred to as the chlamydial stress response) when exposed to penicillin G in culture. Notably, penicillin G-exposed chlamydiae can reenter the normal developmental cycle upon drug removal and are resistant to azithromycin-mediated killing. Because penicillin G is less frequently prescribed than other β-lactams, the clinical relevance of penicillin G-induced chlamydial persistence/stress has been questioned. The goal of this study was to determine whether more commonly used penicillins also induce C. trachomatis serovar E persistence/stress. All penicillins tested, as well as clavulanic acid, induced formation of aberrant, enlarged reticulate bodies (RB) (called aberrant bodies or AB) characteristic of persistent/stressed chlamydiae. Exposure to the penicillins and clavulanic acid also reduced chlamydial infectivity by >95%. None of the drugs tested significantly reduced chlamydial unprocessed 16S rRNA or genomic DNA accumulation, indicating that the organisms were viable, though non-infectious. Finally, recovery assays demonstrated that chlamydiae rendered essentially non-infectious by exposure to ampicillin, amoxicillin, carbenicillin, piperacillin, penicillin V, and clavulanic acid recovered infectivity after antibiotic removal. These data definitively demonstrate that several commonly used penicillins induce C. trachomatis persistence/stress at clinically relevant concentrations.
    Frontiers in Cellular and Infection Microbiology 04/2014; 4:44. DOI:10.3389/fcimb.2014.00044 · 2.62 Impact Factor
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