Genetic variation in TLR10 is not associated with chronic Q fever, despite the inhibitory effect of TLR10 on Coxiella burnetii-induced cytokines in vitro

ABSTRACT Coxiella burnetii is a zoonotic bacterial obligate intracellular parasite and the cause of query (Q) fever. During natural infection of female animals, C. burnetii shows tropism for the placenta and is associated with late-term abortion, at which time the pathogen titer in placental tissue can exceed one billion bacteria per gram. During later stages of pregnancy, placental trophoblasts serve as the major source of progesterone, a steroid hormone known to affect the replication of some pathogens. During infection of placenta-derived JEG-3 cells, C. burnetii showed sensitivity to progesterone but not the immediate precursor pregnenolone or estrogen, another major mammalian steroid hormone. Using host cell-free culture, progesterone was determined to have a direct inhibitory effect on C. burnetii replication. Synergy between the inhibitory effect of progesterone and the efflux pump inhibitors verapamil and 1-(1-naphthylmethyl)-piperazine is consistent with a role for efflux pumps in preventing progesterone-mediated inhibition of C. burnetii activity. The sensitivity of C. burnetii to progesterone, but not structurally related molecules, is consistent with the ability of progesterone to influence pathogen replication in progesterone-producing tissues.

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The Effect of pH on Antibiotic Efficacy against Coxiella burnetii in Axenic Media

Scientific Reports ◽

10.1038/s41598-019-54556-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Cody B. Smith ◽

Charles Evavold ◽

Gilbert J. Kersh

Keyword(s):

Coxiella Burnetii ◽

Antimicrobial Agents ◽

Q Fever ◽

Antimicrobial Treatment ◽

Etiologic Agent ◽

Growth And Survival ◽

Intracellular Compartments ◽

The Impact

AbstractCoxiella burnetii, the etiologic agent of Q fever, replicates in an intracellular phagolysosome with pH between 4 and 5. The impact of this low pH environment on antimicrobial treatment is not well understood. An in vitro system for testing antibiotic susceptibility of C. burnetii in axenic media was set up to evaluate the impact of pH on C. burnetii growth and survival in the presence and absence of antimicrobial agents. The data show that C. burnetii does not grow in axenic media at pH 6.0 or higher, but the organisms remain viable. At pH of 4.75, 5.25, and 5.75 moxifloxacin, doxycycline, and rifampin are effective at preventing growth of C. burnetii in axenic media, with moxifloxacin and doxycycline being bacteriostatic and rifampin having bactericidal activity. The efficacy of doxycycline and moxifloxacin improved at higher pH, whereas rifampin activity was pH independent. Hydroxychloroquine is thought to inhibit growth of C. burnetii in vivo by raising the pH of typically acidic intracellular compartments. It had no direct bactericidal or bacteriostatic activity on C. burnetii in axenic media, suggesting that raising pH of acidic intracellular compartments is its primary mechanism of action in vivo. The data suggest that doxycycline and hydroxychloroquine are primarily independent bacteriostatic agents.

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A combination of interferon-gamma and interleukin-2 production by Coxiella burnetii-stimulated circulating cells discriminates between chronic Q fever and past Q fever

Clinical Microbiology and Infection ◽

10.1111/1469-0691.12423 ◽

2014 ◽

Vol 20 (7) ◽

pp. 642-650 ◽

Cited By ~ 21

Author(s):

T. Schoffelen ◽

T. Sprong ◽

C.P. Bleeker-Rovers ◽

M.C.A. Wegdam-Blans ◽

A. Ammerdorffer ◽

...

Keyword(s):

Interferon Gamma ◽

Coxiella Burnetii ◽

Q Fever ◽

Interleukin 2 ◽

Circulating Cells ◽

Chronic Q Fever

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Chronic Q Fever with Vascular Involvement: Progressive Abdominal Pain in a Patient with Aortic Aneurysm Repair in the United States

Case Reports in Infectious Diseases ◽

10.1155/2019/5369707 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Zanthia Wiley ◽

Sujan Reddy ◽

Kara M. Jacobs Slifka ◽

David C. Brandon ◽

John Jernigan ◽

...

Keyword(s):

United States ◽

Abdominal Pain ◽

Aortic Aneurysm ◽

Coxiella Burnetii ◽

Q Fever ◽

Antibody Detection ◽

Vascular Involvement ◽

Chronic Q Fever ◽

Aneurysm Repair ◽

Aortic Aneurysm Repair

Q fever is a zoonotic bacterial infection caused by Coxiella burnetii. Chronic Q fever comprises less than five percent of all Q fever cases and, of those, endocarditis is the most common presentation (up to 78% of cases), followed by vascular involvement. Risk factors for chronic Q fever with vascular involvement include previous vascular surgery, preexisting valvular defects, aneurysms, and vascular prostheses. The most common symptoms of chronic Q fever with vascular involvement are nonspecific, including weight loss, fatigue, and abdominal pain. Criteria for diagnosis of chronic Q fever include clinical evidence of infection and laboratory criteria (antibody detection, detection of Coxiella burnetii DNA, or growth in culture). Treatment of chronic Q fever with vascular involvement includes a prolonged course of doxycycline and hydroxychloroquine (≥18 months) as well as early surgical intervention, which has been shown to improve survival. Mortality is high in untreated chronic Q fever. We report a case of chronic Q fever with vascular involvement in a 77-year-old man with prior infrarenal aortic aneurysm repair, who lived near a livestock farm in the southeastern United States.

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Bacteriostatic and Bactericidal Activities of Tigecycline against Coxiella burnetii and Comparison with Those of Six Other Antibiotics

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01424-08 ◽

2009 ◽

Vol 53 (6) ◽

pp. 2690-2692 ◽

Cited By ~ 11

Author(s):

Ioanna Spyridaki ◽

Anna Psaroulaki ◽

Iosif Vranakis ◽

Yannis Tselentis ◽

Achilleas Gikas

Keyword(s):

Coxiella Burnetii ◽

Q Fever ◽

Vero Cells ◽

In Vitro Susceptibility ◽

Shell Vial ◽

Bactericidal Activities ◽

Acute Q Fever ◽

Reference Strains ◽

Shell Vial Assay

ABSTRACT The present article is a study of the in vitro susceptibility of eight Greek Coxiella burnetii isolates, derived from patients with acute Q fever, and two reference strains of Coxiella burnetii to tigecycline. The bacteriostatic activity of tigecycline was compared with those of six other antibiotics using a shell vial assay. The MICs of the examined antibiotics were as follows: tigecycline ranged from 0.25 to 0.5 μg/ml; doxycycline, trovafloxacin, and ofloxacin ranged from 1 to 2 μg/ml; linezolid and clarithromycin ranged from 2 to 4 μg/ml; and ciprofloxacin ranged from 4 to 8 μg/ml. Tigecycline was effective in inhibiting the infection of Vero cells by C. burnetii. No bactericidal activity was observed against C. burnetii at 4 μg/ml.

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Coxiella burnetii Interaction with Neutrophils and MacrophagesIn Vitroand in SCID Mice following Aerosol Infection

Infection and Immunity ◽

10.1128/iai.00973-13 ◽

2013 ◽

Vol 81 (12) ◽

pp. 4604-4614 ◽

Cited By ~ 18

Author(s):

Alexandra Elliott ◽

Ying Peng ◽

Guoquan Zhang

Keyword(s):

Immune Response ◽

Coxiella Burnetii ◽

Q Fever ◽

Natural Infection ◽

Scid Mice ◽

Innate Immune ◽

Content Type ◽

Aerosol Infection

ABSTRACTCoxiella burnetiiis an obligate intracellular bacterium that causes acute and chronic Q fever in humans. Human Q fever is mainly transmitted by aerosol infection. However, there is a fundamental gap in the knowledge regarding the mechanisms of pulmonary immunity againstC. burnetiiinfection. This study focused on understanding the interaction betweenC. burnetiiand innate immune cellsin vitroandin vivo. Both virulentC. burnetiiNine Mile phase I (NMI) and avirulent Nine Mile phase II (NMII) were able to infect neutrophils, while the infection rates were lower than 29%, suggesting thatC. burnetiican infect neutrophils, but infection is limited. Interestingly,C. burnetiiinside neutrophils can infect and replicate within macrophages, suggesting that neutrophils cannot killC. burnetiiandC. burnetiimay be using infection of neutrophils as an evasive strategy to infect macrophages. To elucidate the mechanisms of the innate immune response toC. burnetiinatural infection, SCID mice were exposed to aerosolizedC. burnetii. Surprisingly, neutrophil influx into the lungs was delayed until day 7 postinfection in both NMI- and NMII-infected mice. This result suggests that neutrophils may play a unique role in the early immune response against aerosolizedC. burnetii. Studying the interaction betweenC. burnetiiand the innate immune system can provide a model system for understanding how the bacteria evade early immune responses to cause infection.

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Animals withCoxiella burnetiiInfection Demonstrate a Western Immunoblot Profile of Chronic Q Fever in Humans

Canadian Journal of Infectious Diseases ◽

10.1155/1996/853518 ◽

1996 ◽

Vol 7 (1) ◽

pp. 45-48

Author(s):

TJ Marrie ◽

Linda Yates

Keyword(s):

Immune Response ◽

Phase I ◽

Phase Ii ◽

Coxiella Burnetii ◽

Q Fever ◽

Western Immunoblotting ◽

Western Immunoblot ◽

Chronic Q Fever

Western immunoblotting was used to compare the immune response toCoxiella burnetiiphase I and phase II antigens of humans with acute and chronic Q fever with that of infected cats, rabbits, cows and raccoons. The cats, rabbits, cows and raccoons had an immunoblot profile similar to that of the human with chronic Q fever.

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Development of anEx VivoTissue Platform To Study the Human Lung Response to Coxiella burnetii

Infection and Immunity ◽

10.1128/iai.00012-16 ◽

2016 ◽

Vol 84 (5) ◽

pp. 1438-1445 ◽

Cited By ~ 12

Author(s):

Joseph G. Graham ◽

Caylin G. Winchell ◽

Richard C. Kurten ◽

Daniel E. Voth

Keyword(s):

Coxiella Burnetii ◽

Lung Tissue ◽

Human Lung ◽

Q Fever ◽

Ex Vivo ◽

Parasitophorous Vacuole ◽

Inflammasome Activation ◽

Human Lung Tissue ◽

Content Type

Coxiella burnetiiis an intracellular bacterial pathogen that causes human Q fever, an acute debilitating flu-like illness that can also present as chronic endocarditis. Disease typically occurs following inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In human cells,C. burnetiigenerates a replication niche termed the parasitophorous vacuole (PV) by directing fusion with autophagosomes and lysosomes.C. burnetiirequires this lysosomal environment for replication and uses a Dot/Icm type IV secretion system to generate the large PV. However, we do not understand howC. burnetiievades the intracellular immune surveillance that triggers an inflammatory response. We recently characterized human alveolar macrophage (hAM) infectionin vitroand found that avirulentC. burnetiitriggers sustained interleukin-1β (IL-1β) production. Here, we evaluated infection ofex vivohuman lung tissue, defining a valuable approach for characterizingC. burnetiiinteractions with a human host. Within whole lung tissue,C. burnetiipreferentially replicated in hAMs. Additionally, IL-1β production correlated with formation of an apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)-dependent inflammasome in response to infection. We also assessed potential activation of a human-specific noncanonical inflammasome and found that caspase-4 and caspase-5 are processed during infection. Interestingly, although inflammasome activation is closely linked to pyroptosis, lytic cell death did not occur followingC. burnetii-triggered inflammasome activation, indicating an atypical response after intracellular detection. Together, these studies provide a novel platform for studying the human innate immune response toC. burnetii.

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