scholarly journals Assaying Chlamydia pneumoniae persistence in monocyte-derived macrophages identifies schisandrin lignans as phenotypic switchers

2019 ◽  
Author(s):  
Eveliina Taavitsainen ◽  
Maarit Kortesoja ◽  
Leena Hanski
Keyword(s):  
Chlamydia Pneumoniae ◽  
Redox Status ◽  
Productive Infection ◽  
Respiratory Pathogen ◽  
Steady Increase ◽  
Intracellular Bacteria ◽  
Success Factor ◽  
Antibacterial Drug ◽  
Copy Numbers ◽  
Cell Redox Status

AbstractAntibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. Taking persisters into account in susceptibility assays is thus an essential success factor in antibacterial drug discovery. The virulence of the obligate intracellular bacterium Chlamydia pneumoniae is tightly linked to its propensity for persistence, but current susceptibility screening on this gram-negative respiratory pathogen relies on permissive epithelial cells. To establish an improved antichlamydial susceptibility assay allowing the analysis of both actively growing and persister bacteria, we studied C. pneumoniae clinical isolate CV-6 infection kinetics in THP-1 macrophages by qPCR and quantitative culture. Indicated by the steady increase of chlamydial genome copy numbers and infectious progeny as well as the failure of azithromycin to eradicate the intracellular forms of the bacterium, the macrophages were found to harbor a subpopulation of persister C. pneumoniae cells. The potential of the assay for the discovery of anti-persister molecules against intracellular bacteria was demonstrated by the identification of the differential effects of two dibenzocyclooctadiene lignans on C. pneumoniae infection. While schisandrin reverted C. pneumoniae persistence and promoted productive infection, schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection. The phenotypic switch was associated with the suppression of cellular glutathione pools, implying that targeting glutathione homeostasis may provide a novel means for intracellular bacteria resuscitation. In conclusion, these data highlight the value of macrophages over permissive cell lines in anti-persister agent discovery on intracellular bacteria and targeting host cell redox status to fight persistent infections.

scholarly journals Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 294 ◽  
Author(s):  
Eveliina Taavitsainen ◽  
Maarit Kortesoja ◽  
Tanja Bruun ◽  
Niklas G. Johansson ◽  
Leena Hanski
Keyword(s):  
Chlamydia Pneumoniae ◽  
Concomitant Administration ◽  
Productive Infection ◽  
Intracellular Bacteria ◽  
Bacterial Eradication ◽  
Human Pathogen ◽  
Quantitative Culture ◽  
Phenotypic Switch ◽  
Host Interactions ◽  
Adjuvant Therapies

Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia–host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.

Chlamydia pneumoniae as a respiratory pathogen

10.2741/hahn ◽  
2002 ◽  
Vol 7 (1-3) ◽  
pp. e66 ◽  
Author(s):  
David, L. Hahn
Keyword(s):  
Chlamydia Pneumoniae ◽  
Respiratory Pathogen

scholarly journals Docosahexaenoic acid enhances the antioxidant response of human fibroblasts by upregulating γ-glutamyl-cysteinyl ligase and glutathione reductase

2006 ◽  
Vol 95 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Khelifa Arab ◽  
Adrien Rossary ◽  
Françoise Flourié ◽  
Yves Tourneur ◽  
Jean-Paul Steghens
Keyword(s):  
Glutathione Reductase ◽  
Time Course ◽  
Human Fibroblasts ◽  
Fibroblast Cell ◽  
Antioxidant Response ◽  
Redox Status ◽  
Potent Effect ◽  
Time Course Study ◽  
Dose Response Effect ◽  
Cell Redox Status

The chemopreventive effects of dietaryn-3 PUFA in various pathologies has so far remained controversial, and we were interested in studying their potential influence on cell redox status. DHA (22:6n-3), a typical highly unsaturatedn-3 PUFA, was used at 30µmol/l in a model of human fibroblast cell culture. A dose–response effect, roughly linear, was checked for DHA between 0 and 60µmol/l, and was accompanied by a large increase in intracellular GSH content. A time course study of this effect shows that, after a short fall, as soon as 4h after the beginning of the experiment, the large increase in the GSH content was associated with elevated catalytic activities of γ-glutamyl-cysteinyl ligase, glutathione reductase and glutathioneS-transferase. This coordinated response is characteristic of an antioxidant response and was confirmed by the induction of expression of mRNA for γ-glutamyl-cysteinyl ligase, glutathione reductase and haem-oxygenase. This large increase in the GSH content contributes to decreasing the reactive oxygen species level, as assessed by the decreased accumulation of dichlorofluorescein inside cells. To our knowledge, this is the first report on a specific and potent effect of DHA for decreasing the oxidative stress of human fibroblasts.

Blood cell redox status and fatty acids

1995 ◽  
Vol 52 (2-3) ◽  
pp. 159-161 ◽  
Author(s):  
M. Lagarde ◽  
E. Véricel ◽  
B. Chabannes ◽  
A.F. Prigent
Keyword(s):  
Fatty Acids ◽  
Blood Cell ◽  
Redox Status ◽  
Cell Redox Status

Anti-P. gingivalis Response Correlates with Atherosclerosis

2007 ◽  
Vol 86 (1) ◽  
pp. 35-40 ◽  
Author(s):  
P.J. Ford ◽  
E. Gemmell ◽  
P. Timms ◽  
A. Chan ◽  
F.M. Preston ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Chlamydia Pneumoniae ◽  
Molecular Mimicry ◽  
Respiratory Pathogen ◽  
Lesion Area ◽  
Lesion Development ◽  
Pathogen Burden ◽  
Antibody Levels ◽  
Deficient Mice

Significant associations between atherosclerosis and both Porphyromonas gingivalis, a major periodontopathogen, and the respiratory pathogen, Chlamydia pneumoniae, have been shown. Many individuals with evidence of atherosclerosis demonstrate seropositivity to these pathogens. The aim of the present study was to examine the atherogenic effect of repeated immunizations with either or both of these agents, and to determine if molecular mimicry of bacterial heat-shock protein (HSP), termed GroEL, and host (h) HSP60 was involved. Atherogenesis was examined in apolipoprotein-E-deficient (−/−) mice following intraperitoneal immunizations with P. gingivalis, C. pneumoniae, P. gingivalis, and C. pneumoniae or vehicle. Lesion area in the proximal aorta and levels of serum antibodies to P. gingivalis, C. pneumoniae, and GroEL were measured. The increased pathogen burden of P. gingivalis, but not of C. pneumoniae, enhanced atherosclerosis. hHSP60 was detected in lesions, and in P. gingivalis-immunized mice, lesion development was correlated with anti-GroEL antibody levels, supporting the involvement of molecular mimicry between GroEL and hHSP60.

scholarly journals Chlamydia pneumoniae and chronic asthma: Updated systematic review and meta-analysis of population attributable risk

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250034
Author(s):  
David L. Hahn
Keyword(s):  
Chlamydia Pneumoniae ◽  
Population Attributable Risk ◽  
Asthma Severity ◽  
Specific Ige ◽  
Attributable Risk ◽  
Respiratory Pathogen ◽  
Chronic Asthma ◽  
Case Control Studies ◽  
Specific Igg ◽  
Population Attributable Risks

Background Chlamydia pneumoniae (Cp) is an obligate intracellular human respiratory pathogen producing persisting lung infection with a plausible link to asthma pathogenesis. The population attributable risk of potentially treatable Cp infection in asthma has not been reported. Methods The author searched from 2000 to 2020 inclusive for previously un-reviewed and new cross sectional and prospective controlled studies of Cp biomarkers and chronic asthma in both children and adults. Qualitative descriptive results and quantitative estimates of population attributable risk for selected biomarkers (specific IgG, IgA and IgE) are presented. Findings No large, long-term prospective population-based studies of Cp infection and asthma were identified. About half of case-control studies reported one or more significant associations of Cp biomarkers and chronic asthma. Heterogeneity of results by age group (pediatric v adult asthma), severity category (severe/uncontrolled, moderate/partly controlled, mild/controlled) and antibody isotype (specific IgG, IgA, IgE) were suggested by the qualitative results and confirmed by meta-analyses. The population attributable risks for Cp-specific IgG and IgA were nul in children and were 6% (95% confidence interval 2%-10%, p = 0.002) and 13% (9%-18%, p<0.00001) respectively in adults. In contrast to the nul or small population attributable risks for Cp-specific IgG and IgA, the population attributable risk for C. pneumoniae-specific IgE (children and adults combined) was 47% (39%-55%, p<0.00001). In the subset of studies that reported on asthma severity categories, Cp biomarkers were positively and significantly (P<0.00001) associated with asthma severity. Interpretation C. pneumoniae-specific IgE is strongly associated with asthma and asthma severity, suggesting a possible mechanism linking chronic Cp infection with asthma in a subset of individuals with asthma. Infection biomarkers should be included in future macrolide treatment trials for severe and uncontrolled asthma.

scholarly journals Failure To Detect Chlamydia pneumoniaein the Late-Onset Alzheimer's Brain

2000 ◽  
Vol 38 (7) ◽  
pp. 2591-2594 ◽  
Author(s):  
Robert H. Ring ◽  
Joseph M. Lyons
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chlamydia Pneumoniae ◽  
Late Onset ◽  
Brain Regions ◽  
Postmortem Brain ◽  
Respiratory Pathogen ◽  
Specific Gene ◽  
Tissue Samples ◽  
Postmortem Brain Tissue

Epidemiological studies have yet to identify a single cause for the most common late-onset form of Alzheimer's disease. The common respiratory pathogen Chlamydia pneumoniae recently has been implicated as a risk factor for this form of Alzheimer's disease. Were this true, there would be a dramatic shift in current paradigms of Alzheimer's disease research and treatment. In the absence of published confirmation, we obtained postmortem brain tissue from late-onset Alzheimer's disease patients (n = 15) and representative controls (n = 5) and extracted DNA from up to six separate brain regions in each instance, including those areas particularly relevant to Alzheimer's disease neuropathology. Each sample of DNA (n = 101) was assayed five times or more for the presence of C. pneumoniae DNA using a nested-PCR protocol targeting a species-specific gene sequence coding for the major outer membrane protein of this organism. We were unable unequivocally to detect C. pneumoniae in any of the 101 samples tested by PCR and failed to culture the organism from tissue samples. We conclude that C. pneumoniae is neither strongly nor uniquely associated with the neuropathology seen in late-onset Alzheimer's disease.

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