scholarly journals Coxiella burnetii Inhibits Activation of Host Cell Apoptosis through a Mechanism That Involves Preventing Cytochrome c Release from Mitochondria

2007 ◽  
Vol 75 (11) ◽  
pp. 5282-5289 ◽  
Author(s):  
Anja Lührmann ◽  
Craig R. Roy
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Coxiella Burnetii ◽  
Mammalian Cells ◽  
Q Fever ◽  
Host Cells ◽  
Intracellular Pathogen ◽  
Obligate Intracellular ◽  
Cell Death Pathway ◽  
Obligate Intracellular Pathogen

ABSTRACT Coxiella burnetii is an obligate intracellular pathogen and the etiological agent of the human disease Q fever. C. burnetii infects mammalian cells and then remodels the membrane-bound compartment in which it resides into a unique lysosome-derived organelle that supports bacterial multiplication. To gain insight into the mechanisms by which C. burnetii is able to multiply intracellularly, we examined the ability of host cells to respond to signals that normally induce apoptosis. Our data show that mammalian cells infected with C. burnetii are resistant to apoptosis induced by staurosporine and UV light. C. burnetii infection prevented caspase 3/7 activation and limited fragmentation of the host cell nucleus in response to agonists that induce apoptosis. Inhibition of bacterial protein synthesis reduced the antiapoptotic effect that C. burnetii exerted on infected host cells. Inhibition of apoptosis in C. burnetii-infected cells did not correlate with the degradation of proapoptotic BH3-only proteins involved in activation of the intrinsic cell death pathway; however, cytochrome c release from mitochondria was diminished in cells infected with C. burnetii upon induction of apoptosis. These data indicate that C. burnetii can interfere with the intrinsic cell death pathway during infection by producing proteins that either directly or indirectly prevent release of cytochrome c from mitochondria. It is likely that inhibition of apoptosis by C. burnetii represents an important virulence property that allows this obligate intracellular pathogen to maintain host cell viability despite inducing stress that would normally activate the intrinsic death pathway.

scholarly journals Seroprevalence of Coxiella burnetii in cattle in the Belgrade epizootiological area

2020 ◽  
Vol 36 (3) ◽  
pp. 359-369
Author(s):  
Jadranka Zutic ◽  
Dragica Vojinovic ◽  
Slobodan Stanojevic ◽  
Branislav Kureljusic ◽  
Vesna Milicevic ◽  
...  
Keyword(s):  
Coxiella Burnetii ◽  
Preventive Measures ◽  
Q Fever ◽  
Intracellular Pathogen ◽  
Reproductive Disorders ◽  
Serum Samples ◽  
Obligate Intracellular ◽  
Control Programs ◽  
Serological Studies ◽  
Obligate Intracellular Pathogen

Q-fever is antropozoonosis which is caused by Coxiella burnetii, obligate intracellular pathogen. The most significant characteristics of this pathogen are resistance and stability in the environment, possibility of aerosol dissemination, and very low infective dose. C. burnetii can infect domestic and wild animals, rodents, birds and ticks. Q fever in animals is generally asymptomatic, although it can lead to reproductive disorders during pregnancy. The main route of infection in humans is inhalation of contaminated aerosol and dust. Serological studies have shown the presence of antibodies to C. burnetii in the serum samples of cattle in Belgrade epizootiological area. Seroprevalence of 18% was found in farm bred cattle, while it was only 1.5% in individual breeding. In farm bred cows that have suffered abortion prevalence was 49%, and only 1.9% in individual breeding. The overall results indicate that the circulation of this pathogen in cattle, in Belgrade epizootiological area, poses a health risk, not only to the cattle, but also to the humans, especially persons working with animals. Q fever control programs most often recommend serological research and vaccination of animals. Accordingly, it is necessary to define a strategy for the implementation of biosecurity measures and preventive measures against Q fever.

Cell death and inflammation during infection with the obligate intracellular pathogen, Chlamydia

Biochimie ◽  
2003 ◽  
Vol 85 (8) ◽  
pp. 763-769 ◽  
Author(s):  
Jean-Luc Perfettini ◽  
Véronique Hospital ◽  
Lynn Stahl ◽  
Thomas Jungas ◽  
Philippe Verbeke ◽  
...  
Keyword(s):  
Cell Death ◽  
Intracellular Pathogen ◽  
Obligate Intracellular ◽  
Obligate Intracellular Pathogen

scholarly journals Dependency of Coxiella burnetii Type 4B Secretion on the Chaperone IcmS

2019 ◽  
Vol 201 (23) ◽  
Author(s):  
Charles L. Larson ◽  
Paul A. Beare ◽  
Robert A. Heinzen
Keyword(s):  
Host Cell ◽  
Coxiella Burnetii ◽  
Legionella Pneumophila ◽  
Q Fever ◽  
Secretion System ◽  
Host Cells ◽  
Growth Defect ◽  
Wild Type ◽  
Signal Sequences ◽  
Content Type

ABSTRACT Macrophage parasitism by Coxiella burnetii, the cause of human Q fever, requires the translocation of proteins with effector functions directly into the host cell cytosol via a Dot/Icm type 4B secretion system (T4BSS). Secretion by the analogous Legionella pneumophila T4BSS involves signal sequences within the C-terminal and internal domains of effector proteins. The cytoplasmic chaperone pair IcmSW promotes secretion and binds internal sites distinct from signal sequences. In the present study, we investigated requirements of C. burnetii IcmS for host cell parasitism and effector translocation. A C. burnetii icmS deletion mutant (ΔicmS) exhibited impaired replication in Vero epithelial cells, deficient formation of the Coxiella-containing vacuole, and aberrant T4BSS secretion. Three secretion phenotypes were identified from a screen of 50 Dot/Icm substrates: IcmS dependent (secreted by only wild-type bacteria), IcmS independent (secreted by both wild-type and ΔicmS bacteria), or IcmS inhibited (secreted by only ΔicmS bacteria). Secretion was assessed for N-terminal or C-terminal truncated forms of CBU0794 and CBU1525. IcmS-inhibited secretion of CBU1525 required a C-terminal secretion signal whereas IcmS-dependent secretion of CBU0794 was directed by C-terminal and internal signals. Interchange of the C-terminal 50 amino acids of CBU0794 and CBU1525 revealed that sites within the C terminus regulate IcmS dependency. Glutathione S-transferase-tagged IcmSW bound internal sequences of IcmS-dependent and -inhibited substrates. Thus, the growth defect of the C. burnetii ΔicmS strain is associated with a loss of T4BSS chaperone activity that both positively and negatively regulates effector translocation. IMPORTANCE The intracellular pathogen Coxiella burnetii employs a type 4B secretion system (T4BSS) that promotes growth by translocating effectors of eukaryotic pathways into host cells. T4BSS regulation modeled in Legionella pneumophila indicates IcmS facilitates effector translocation. Here, we characterized type 4B secretion by a Coxiella ΔicmS mutant that exhibits intracellular growth defects. T4BSS substrates demonstrated increased, equivalent, or decreased secretion by the ΔicmS mutant relative to wild-type Coxiella. Similar to the Legionella T4BSS, IcmS dependency in Coxiella was determined by C-terminal and/or internal secretion signals. However, IcmS inhibited secretion of some effectors by Coxiella that were previously shown to be translocated by Legionella. Thus, Coxiella has a unique IcmS regulatory mechanism that both positively and negatively regulates T4BSS export.

scholarly journals Hijacking and Use of Host Kinases by Chlamydiae

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1034
Author(s):  
Prakash Sah ◽  
Erika I. Lutter
Keyword(s):  
Host Cell ◽  
Intracellular Pathogen ◽  
Host Proteins ◽  
Sexually Transmitted ◽  
Obligate Intracellular ◽  
Host Cell Apoptosis ◽  
Survival And Development ◽  
Causative Agents ◽  
Cell Processes ◽  
Obligate Intracellular Pathogen

Chlamydia species are causative agents of sexually transmitted infections, blinding trachoma, and animal infections with zoonotic potential. Being an obligate intracellular pathogen, Chlamydia relies on the host cell for its survival and development, subverting various host cell processes throughout the infection cycle. A key subset of host proteins utilized by Chlamydia include an assortment of host kinase signaling networks which are vital for many chlamydial processes including entry, nutrient acquisition, and suppression of host cell apoptosis. In this review, we summarize the recent advancements in our understanding of host kinase subversion by Chlamydia.

scholarly journals Chlamydia trachomatis Species-Specific Induction of Ezrin Tyrosine Phosphorylation Functions in Pathogen Entry

2007 ◽  
Vol 75 (12) ◽  
pp. 5669-5677 ◽  
Author(s):  
Kena A. Swanson ◽  
Deborah D. Crane ◽  
Harlan D. Caldwell
Keyword(s):  
Chlamydia Trachomatis ◽  
Host Cell ◽  
Tyrosine Phosphorylation ◽  
Mammalian Cells ◽  
Dominant Negative ◽  
Host Protein ◽  
Host Cells ◽  
Obligate Intracellular Pathogen ◽  
Pathogen Entry ◽  
Species Specific

ABSTRACT Chlamydia trachomatis is an obligate intracellular pathogen of humans that exhibits species-specific biological characteristics in its early interactions with host cells that are likely important to pathogenesis. One such characteristic is the tyrosine phosphorylation (Tyr-P) of an ∼70-kDa polypeptide that occurs only after infection of mammalian cells by human strains. We sought to identify this protein because of its potential significance to the pathogenesis of human chlamydial infections. Using an immunoproteomic approach we identified the host protein ezrin, a member of the ezrin-radixin-moesin (ERM) protein family that serves as a physical link between host cell receptors and the actin cytoskeleton. Confocal microscopy studies showed colocalization of ezrin and actin at the tips and crypts of microvilli, the site of chlamydial attachment and entry, respectively. To demonstrate a functional role for ezrin we infected cells with a dominant-negative (DN) ezrin phenotype or treated cells with ezrin-specific small interfering RNA (siRNA). We found that both DN and siRNA-treated cells were significantly less susceptible to infection by human chlamydial strains. Moreover, we demonstrated that inhibition of infection in ezrin DN cells occurred at the stage of chlamydial entry. We hypothesize that the C. trachomatis-specific Tyr-P of ezrin might relate to an undefined species-specific mechanism of pathogen entry that involves chlamydial specific ligand(s) and host cell coreceptor usage.

scholarly journals Coxiella burnetii Inhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages

2007 ◽  
Vol 75 (9) ◽  
pp. 4263-4271 ◽  
Author(s):  
Daniel E. Voth ◽  
Dale Howe ◽  
Robert A. Heinzen
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Coxiella Burnetii ◽  
Alveolar Macrophages ◽  
Q Fever ◽  
Apoptotic Cell ◽  
Parp Cleavage ◽  
Potent Inducer ◽  
Infected Cells ◽  
Infectious Cycle

ABSTRACT Coxiella burnetii, the cause of human Q fever, is an aerosol-borne, obligate intracellular bacterium that targets host alveolar mononuclear phagocytic cells during infection. In all cell types examined, C. burnetii establishes a replicative niche in a lysosome-like parasitophorous vacuole where it carries out a lengthy infectious cycle with minimal cytopathic effects. The persistent and mild nature of C. burnetii infection in vitro suggests that the pathogen modulates apoptosis to sustain the host cell. In the current study, we examined the ability of C. burnetii to inhibit apoptotic cell death during infection of human THP-1 monocyte-derived macrophages and primary monkey alveolar macrophages. C. burnetii-infected cells demonstrated significant protection from death relative to uninfected cells following treatment with staurosporine, a potent inducer of intrinsic apoptosis. This protection correlated with reduced cleavage of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP), all proteolytic events that occur during apoptosis. Reduced PARP cleavage was also observed in cells treated with tumor necrosis factor alpha to induce extrinsic apoptosis. Apoptosis inhibition was a C. burnetii-driven process as infected cells treated with rifampin or chloramphenicol, inhibitors of bacterial RNA and protein synthesis, respectively, showed significantly reduced protection against staurosporine-induced apoptosis. C. burnetii infection affected the expression of multiple apoptosis-related genes and resulted in increased synthesis of the antiapoptotic proteins A1/Bfl-1 and c-IAP2. Collectively, these data suggest that C. burnetii modulates apoptotic pathways to inhibit host cell death, thus providing a stable, intracellular niche for the course of the pathogen's infectious cycle.

scholarly journals Coxiella burnetii in Infertile Dairy Cattle With Chronic Endometritis

2018 ◽  
Vol 55 (4) ◽  
pp. 539-542 ◽  
Author(s):  
Davide De Biase ◽  
Alessandro Costagliola ◽  
Fabio Del Piero ◽  
Rossella Di Palo ◽  
Domenico Coronati ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Coxiella Burnetii ◽  
Animal Species ◽  
Bacterial Culture ◽  
Q Fever ◽  
Premature Delivery ◽  
Chronic Endometritis ◽  
Obligate Intracellular ◽  
Obligate Intracellular Pathogen ◽  
First Time

Coxiella burnetii is an obligate intracellular pathogen and the cause of Q fever in many animal species and humans. Several studies have reported the association between C. burnetii and abortion, premature delivery, stillbirth, and weak offspring. However, no solid evidence indicates that C. burnetii causes endometritis, subfertility, and retained fetal membranes. For this study, histopathological and PCR evaluation were performed on 40 uterine biopsies from dairy cattle with poor fertility. Uterine swabs were concurrently tested with microbiology assays. The endometrial biopsies of 30 cows did not have any significant lesions, and no pathogens were identified by aerobic bacterial culture and PCR. Ten cows were PCR-positive for C. burnetii and negative for other pathogens by aerobic bacterial culture and PCR. These 10 cases revealed a mild to severe chronic endometritis admixed with perivascular and periglandular fibrosis. Immunohistochemical evaluation of C. burnetii PCR-positive biopsies identified, for the first time, the presence of intralesional and intracytoplasmic C. burnetii in macrophages in the endometrium of cattle.

Sign in / Sign up

Export Citation Format

Share Document