Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by <i>Pseudomonas aeruginosa</i> virulence factor pyocyanin

Qadri, Syed M.; Donkor, David A.; Bhakta, Varsha; Eltringham-Smith, Louise J.; Dwivedi, Dhruva J.; Moore, Jane C.; Pepler, Laura; Ivetic, Nikola; Nazi, Ishac; Fox‐Robichaud, Alison; Liaw, Patricia C.; Sheffield, William P.

doi:10.1111/jcmm.12778

Cited by 80 publications

(60 citation statements)

References 73 publications

(112 reference statements)

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“…aeruginosa can be observed as part of the commensal microbiome of the oral cavity, gut, and skin in healthy humans [26, 29–32]. Though P .…”

Section: Discussionmentioning

confidence: 99%

“…In addition to matrix-degrading proteases and di-rhamnolipid toxin, P . aeruginosa displays an impressive arsenal of other virulence factors including the potent exotoxin A, which, similarly to diphtheria toxin, inhibits protein synthesis of host cells and may remain cytotoxic long after the bacteria have been killed [16, 32]. Also, pyocyanin, a P .…”

Section: Discussionmentioning

confidence: 99%

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Pseudomonas aeruginosa Microcolonies in Coronary Thrombi from Patients with ST-Segment Elevation Myocardial Infarction

et al. 2016

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Chronic infection is associated with an increased risk of atherothrombotic disease and direct bacterial infection of arteries has been suggested to contribute to the development of unstable atherosclerotic plaques. In this study, we examined coronary thrombi obtained in vivo from patients with ST-segment elevation myocardial infarction (STEMI) for the presence of bacterial DNA and bacteria. Aspirated coronary thrombi from 22 patients with STEMI were collected during primary percutaneous coronary intervention and arterial blood control samples were drawn from radial or femoral artery sheaths. Analyses were performed using 16S polymerase chain reaction and with next-generation sequencing to determine bacterial taxonomic classification. In selected thrombi with the highest relative abundance of Pseudomonas aeruginosa DNA, peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) with universal and species specific probes was performed to visualize bacteria within thrombi. From the taxonomic analysis we identified a total of 55 different bacterial species. DNA from Pseudomonas aeruginosa represented the only species that was significantly associated with either thrombi or blood and was >30 times more abundant in thrombi than in arterial blood (p<0.0001). Whole and intact bacteria present as biofilm microcolonies were detected in selected thrombi using universal and P. aeruginosa-specific PNA-FISH probes. P. aeruginosa and vascular biofilm infection in culprit lesions may play a role in STEMI, but causal relationships remain to be determined.

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“…aeruginosa can be observed as part of the commensal microbiome of the oral cavity, gut, and skin in healthy humans [26, 29–32]. Though P .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Microcolonies in Coronary Thrombi from Patients with ST-Segment Elevation Myocardial Infarction

et al. 2016

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“…In extreme cases [e.g., Ref. (133, 1107–1112)], including following infection (1113), this results in eryptosis, the suicidal death of erythrocytes. It is of interest that ceramide, a precursor of sphingosine-1-phosphate (S1P) (Table 7), is raised in various diseases such as Parkinson’s and may serve to stimulate eryptosis (1114).…”

Section: Clotting Coagulopathies and Fibrinogen In Pementioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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“…The adherence of eryptotic cells to vascular wall endothelial CXCL16/SR-PSO [61] and the binding of phosphatidylserine-exposing erythrocytes to blood platelets could further stimulate blood clotting and trigger thrombosis [62]. Eryptosis could also be induced by a wide range of xenobiotics [63-74], and enhanced eryptosis is observed in several clinical conditions, such as systemic lupus erythematosus [75], uremia under hemodialysis or peritoneal dialysis [76], pulmonary tumor [77], Parkinson’s disease [78], arteritis [79], hepatic failure [80, 81], tumor-induced anemia [82], vitamin D excess [83], advanced age [84], G6PD deficiency [85], sepsis [86], APC gene mutation and colon carcinoma [87]. Eryptosis can also be triggered by erythrocyte storage [88-90].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Suicidal Erythrocyte Death by Indirubin-3’-Monoxime

Liu

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Qing Dai is a prized traditional Chinese medicine whose major component, indirubin, and its derivative, indirubin-3’-monoxime (IDM), have inhibitory effects on the growth of many human tumor cells and pronounced anti-leukemic activities. However, the effects of IDM on mature human erythrocytes are unclear. This study aimed to evaluate the potential impact of IDM on erythrocytes and the mechanisms underlying that impact. Methods: Utilizing flow cytometry and confocal laser scanning microscopy, phosphatidylserine exposure at the cell surface was estimated by annexin V-fluorescein isothiocyanate (FITC). The relative cell size, expressed in arbitrary units, was evaluated by forward scatter in a flow cytometer. Fluo-3 fluorescence was used to bewrite changes in cytosolic Ca²⁺ activity, reactive oxygen species (ROS) formation was assessed by 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence, and ceramide abundance was evaluated by FITC-conjugated specific antibodies. Results: The 24-h exposure of human erythrocytes to IDM (12 µM) significantly decreased the percentage of annexin V-binding erythrocytes and the intracellular calcium concentration ([Ca²⁺]_i). IDM (3-12 µM) did not significantly modify the ceramide level or DCFH-DA fluorescence. Energy depletion (removal of glucose for 24 hours) significantly increased annexin V binding and Fluo-3 fluorescence and diminished forward scatter, and these effects were significantly mitigated by IDM (12 µM). Moreover, the Ca²⁺ ionophore ionomycin (1 µM, 60 min) and oxidative stress (30 min exposure to 0.05 mM tert-butyl hydroperoxide, t-BHP) similarly triggered eryptosis, which was also significantly suppressed by IDM. Conclusions: IDM is a novel inhibitor of suicidal erythrocyte death following ionomycin treatment, t-BHP treatment and energy depletion. Thus, IDM may counteract anemia and impairment of microcirculation, at least in part, by inhibition of Ca²⁺ entry into erythrocytes.

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Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin

Cited by 80 publications

References 73 publications

Pseudomonas aeruginosa Microcolonies in Coronary Thrombi from Patients with ST-Segment Elevation Myocardial Infarction

Pseudomonas aeruginosa Microcolonies in Coronary Thrombi from Patients with ST-Segment Elevation Myocardial Infarction

A Dormant Microbial Component in the Development of Preeclampsia

Inhibition of Suicidal Erythrocyte Death by Indirubin-3’-Monoxime

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