Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

ABSTRACT The ketolides HMR 3004 and HMR 3647 (telithromycin) are a new class of macrolides that have a potential clinical efficacy against intracellular pathogens. The objectives of this study were to investigate the MIC, minimum bactericidal concentration, and time-dependent killing of two Chlamydia pneumoniaestrains of the two ketolides. The killing effect was also studied with a newly developed intracellular in vitro kinetic model. Furthermore, HMR 3647 was studied for the effect of a subinhibitory concentration of 0.5 times the MIC after a preexposure of 10 times the MIC during 12 h. The MICs for both strains were 0.0039 and 0.0156 mg/liter for HMR 3004 and HMR 3647, respectively. Killing with 10 times the MIC was time dependent, increasing from a 1-log-unit decrease in the number of inclusions per well at 48 h to a maximal effect of 2.8-log-unit decrease after 96 h. A preexposure of 10 times the MIC of HMR 3647 for 12 h followed by a subinhibitory concentration of 0.5 times the MIC increased the killing effect to a 1.2-log-unit reduction in inclusions per well. An exposure for 12 h gave poor reduction of inclusions, while a static dose of 10 times the MIC for 72 h showed a 2.2-log-unit reduction in inclusions per well. In the kinetic model, a small number of inclusions were detected after 72 h by one exposure of 10 times the MIC. Regrowth could not be detected after 120 h. The ketolides HMR 3004 and HMR 3647 have bactericidal activity and show a significant sub-MIC effect on the intracellular pathogenC. pneumoniae.

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Chlamydia pneumoniae infection of monocytes in vitro stimulates innate and adaptive immune responses relevant to those in Alzheimer’s disease

Journal of Neuroinflammation ◽

10.1186/s12974-014-0217-0 ◽

2014 ◽

Vol 11 (1) ◽

Cited By ~ 15

Author(s):

Charles Lim ◽

Christine J Hammond ◽

Susan T Hingley ◽

Brian J Balin

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune Responses ◽

Chlamydia Pneumoniae ◽

Adaptive Immune Responses ◽

Adaptive Immune

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Could Chlamydia Pneumoniae Be Considered an Infectious Risk Factor for Inflammatory Diseases Such as Atherosclerosis ?

European Journal of Inflammation ◽

10.1177/1721727x0500300301 ◽

2005 ◽

Vol 3 (3) ◽

pp. 109-112

Author(s):

R. Sessa ◽

M. Di Pietro ◽

G. Schiavoni ◽

I. Santino ◽

M. Del Piano

Keyword(s):

Risk Factor ◽

Chlamydia Pneumoniae ◽

Direct Detection ◽

Inflammatory Diseases ◽

Cell Types ◽

Chronic Inflammatory Disease ◽

Upper Respiratory Tract ◽

Infectious Risk ◽

Tract Infections

Chlamydia pneumoniae, a Gram-negative intracellular obligate bacteria, is recognised as a common cause of upper respiratory tract infections, and accounts for ∼10% of community-acquired pneumonia. In recent years, chronic and persistent infection with C. pneumoniae has been implicated in the pathogenesis of atherosclerosis. Atherosclerosis is regarded as a chronic inflammatory disease that results from complex interactions between a variety of cell types such as endothelial cells, vascular smooth muscle cells, monocytes/macrophages and inflammatory mediators. Involvement of C. pneumoniae in the pathogenesis of atherosclerosis has been supported by findings from seroepidemiologic studies, direct detection of chlamydial DNA, experimental animal and in vitro studies, and antibiotic intervention trials. The spectrum of cell biological, animal, and human clinical data suggests that C. pneumoniae may be considered an infectious risk factor for atherosclerosis but further studies are needed to clarify the etiopathogenetic role of C. pneumoniae in atherosclerotic vessel walls.

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In VitroActivity of Omadacycline againstChlamydia pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01907-18 ◽

2018 ◽

Vol 63 (2) ◽

pp. e01907-18 ◽

Cited By ~ 3

Author(s):

Stephan A. Kohlhoff ◽

Natalia Huerta ◽

Margaret R. Hammerschlag

Keyword(s):

Minimum Inhibitory Concentration ◽

Chlamydia Pneumoniae ◽

Inhibitory Concentration ◽

Content Type

ABSTRACTThein vitroactivities of omadacycline, azithromycin, doxycycline, moxifloxacin, and levofloxacin were tested against 15 isolates ofChlamydia pneumoniae. The minimum inhibitory concentration at which 90% of the isolates ofC. pneumoniaewere inhibited by omadacycline was 0.25 μg/ml (range, 0.03 to 0.5 μg/ml).

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Local Immune Responses to Chlamydia pneumoniae in the Lungs of BALB/c Mice during Primary Infection and Reinfection

Infection and Immunity ◽

10.1128/iai.66.11.5113-5118.1998 ◽

1998 ◽

Vol 66 (11) ◽

pp. 5113-5118 ◽

Cited By ~ 46

Author(s):

Jenni M. Penttilä ◽

Marjukka Anttila ◽

Mirja Puolakkainen ◽

Aino Laurila ◽

Kari Varkila ◽

...

Keyword(s):

Primary Infection ◽

Bacterial Infections ◽

Chlamydia Pneumoniae ◽

Mononuclear Cells ◽

Relative Increase ◽

Culturable Bacteria ◽

Ifn Γ ◽

Tissue Reactions

ABSTRACT Cell-mediated immune (CMI) responses play a major role in protection as well as pathogenesis of many intracellular bacterial infections. In this study, we evaluated the infection kinetics and assessed histologically the lymphoid reactions and local, in vitro-restimulated CMI responses in lungs of BALB/c mice, during both primary infection and reinfection with Chlamydia pneumoniae. The primary challenge resulted in a self-restricted infection with elimination of culturable bacteria by day 27 after challenge. A mild lymphoid reaction characterized the pathology in the lungs. In vitro CMI responses consisted of a weak proliferative response and no secretion of gamma interferon (IFN-γ). The number of lung-derived mononuclear cells increased substantially during the primary infection; the largest relative increase was observed in B cells (B220+). After reinfection, the number of lung-derived mononuclear cells increased further, and the response consisted mainly of T cells. The reinfection was characterized in vivo by significant protection from infection (fewer cultivable bacteria in the lungs for a shorter period of time) but increased local lymphoid reaction at the infection site. In vitro, as opposed to the response in naive mice, acquired immunity was characterized by a strongly Th1-biased (IFN-γ) CMI response. These results suggest that repeated infections with C. pneumoniae may induce Th1-type responses with similar associated tissue reactions, as shown in C. trachomatis infection models.

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In Vitro Susceptibilities of Chlamydia pneumoniae Isolates from German Patients and Synergistic Activity of Antibiotic Combinations

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.7.1808 ◽

1999 ◽

Vol 43 (7) ◽

pp. 1808-1810 ◽

Cited By ~ 10

Author(s):

Heike M. Freidank ◽

Philipp Losch ◽

Heike Vögele ◽

Margit Wiedmann-Al-Ahmad

Keyword(s):

Chlamydia Pneumoniae ◽

Synergistic Activity ◽

German Patient ◽

Type Strains

ABSTRACT The susceptibilities of six Chlamydia pneumoniae type strains and of six German patient isolates to erythromycin, azithromycin, roxithromycin, clarithromycin, doxycycline, ofloxacin, and rifampin were investigated. MICs and minimal chlamydicidal concentrations were all within the ranges reported previously. Combinations of azithromycin with either ofloxacin, doxycycline, or rifampin, as well as combinations of three antibiotics (rifampin, azithromycin, and ofloxacin or doxycycline), showed synergistic activity against C. pneumoniae.

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Effect of Prolonged Treatment with Azithromycin, Clarithromycin, or Levofloxacin on Chlamydia pneumoniae in a Continuous-Infection Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.2.409-412.2002 ◽

2002 ◽

Vol 46 (2) ◽

pp. 409-412 ◽

Cited By ~ 54

Author(s):

Andrei Kutlin ◽

Patricia M. Roblin ◽

Margaret R. Hammerschlag

Keyword(s):

Chlamydia Pneumoniae ◽

Day Treatment ◽

Prolonged Treatment ◽

Infection Model ◽

Necrosis Factor Alpha ◽

Persistent Infections ◽

Cytokine Levels ◽

Factor Alpha ◽

Vitro Model

ABSTRACT Persistent infections with Chlamydia pneumoniae have been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1β, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.

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The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/8394818 ◽

2018 ◽

Vol 2018 ◽

pp. 1-25 ◽

Cited By ~ 20

Author(s):

Sha Li ◽

Hor Yue Tan ◽

Ning Wang ◽

Fan Cheung ◽

Ming Hong ◽

...

Keyword(s):

Liver Diseases ◽

Therapeutic Effects ◽

Natural Polyphenols ◽

Action Mechanisms ◽

Liver Injuries ◽

Wide Range ◽

Natural Foods ◽

Systematical Review

Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases. It has been reported that many polyphenols from a wide range of foods and herbs exert therapeutic effects on liver injuries via complicated mechanisms. Therefore, it is necessary to have a systematical review to sort out current researches to help better understand the potentials of polyphenols in liver diseases. In this review, we aim to summarize and update the existing evidence of natural polyphenols in the treatment of various liver diseases by in vitro, in vivo, and clinical studies, while special attention is paid to the action mechanisms.

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Chlamydia pneumoniae Resists Antibiotics in Lymphocytes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.6.1972-1975.2003 ◽

2003 ◽

Vol 47 (6) ◽

pp. 1972-1975 ◽

Cited By ~ 14

Author(s):

Hiroyuki Yamaguchi ◽

Herman Friedman ◽

Mayumi Yamamoto ◽

Keigo Yasuda ◽

Yoshimasa Yamamoto

Keyword(s):

Epithelial Cells ◽

Bacterial Growth ◽

Chlamydia Pneumoniae ◽

Inflammatory Diseases ◽

Lymphoid Cells ◽

Infection Model ◽

Chronic Inflammatory Diseases

ABSTRACT Chlamydia pneumoniae infection of lymphocytes in blood has been well documented, and it is apparent that control of this pathogen in these cells may be critical in the development of chronic inflammatory diseases associated with infection by this bacterium. The activity of antibiotics against C. pneumoniae in lymphocytes was assessed in this study by utilizing an in vitro infection model with lymphoid cells. The results obtained indicated that although all of the antibiotics tested showed remarkable activity against bacterial growth in epithelial cells, C. pneumoniae in lymphocytes was less susceptible to antibiotics than was bacterial growth in epithelial cells, which are widely used for the evaluation of anti-C. pneumoniae antibiotics.

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