A bacterial toxin that cleaves Ras oncoprotein

AbstractObjectivesCardiac damage in patient with diphtheritic myocarditis is reported as the leading cause of mortality. Diphtheria toxin (DTx) is a well-known bacterial toxin inducing various cytotoxic effects. Mainly, catalytic fragment inhibits protein synthesis, induces cytotoxicity, and depolymerizes actin filaments. In this study, we aimed to demonstrate the extent of myofibrillar damage under DTx treatment to porcine cardiac tissue samples.MethodsTissue samples were incubated with DTx for 1–3 h in culture conditions. To analyze whole toxin (both fragments) distribution, conjugation of DTx with FITC was performed. Measurements were carried out with fluorescence spectrophotometer before and after dialysis. Immunofluorescence microscopy was used to show localization of DTx-FITC (15 nM) on cardiac tissue incubated for 2 h. Ultrastructural characterization of cardiac tissue samples treated with DTx (15 or 150 nM) was performed with transmission electron microscopy.ResultsDTx exerts myofibrillar disorganization. Myofilament degeneration, mitochondrial damage, vacuolization, and abundant lipid droplets were determined with 150 nM of DTx treatment.ConclusionsThis finding is an addition to depolymerization of actin filaments as a result of the DTx-actin interactions in in vitro conditions, indicating that myofilament damage can occur with DTx directly besides protein synthesis inhibition. Ultrastructural results support the importance of filamentous actin degeneration at diphtheritic myocarditis.

Download Full-text

Interactions of the Streptococcus pneumoniae Toxin-Antitoxin RelBE Proteins with Their Target DNA

Microorganisms ◽

10.3390/microorganisms9040851 ◽

2021 ◽

Vol 9 (4) ◽

pp. 851

Author(s):

Inmaculada Moreno-Córdoba ◽

Wai-Ting Chan ◽

Concha Nieto ◽

Manuel Espinosa

Keyword(s):

Streptococcus Pneumoniae ◽

Self Regulation ◽

Mrna Translation ◽

Dna Supercoiling ◽

Bacterial Toxin ◽

Type Ii ◽

Cellular Functions ◽

Dna Backbone ◽

Different Strains ◽

Palindromic Sequences

Type II bacterial toxin-antitoxin (TA) systems are found in most bacteria, archaea, and mobile genetic elements. TAs are usually found as a bi-cistronic operon composed of an unstable antitoxin and a stable toxin that targets crucial cellular functions like DNA supercoiling, cell-wall synthesis or mRNA translation. The type II RelBE system encoded by the pathogen Streptococcus pneumoniae is highly conserved among different strains and participates in biofilm formation and response to oxidative stress. Here, we have analyzed the participation of the RelB antitoxin and the RelB:RelE protein complex in the self-regulation of the pneumococcal relBE operon. RelB acted as a weak repressor, whereas RelE performed the role of a co-repressor. By DNA footprinting experiments, we show that the proteins bind to a region that encompasses two palindromic sequences that are located around the −10 sequences of the single promoter that directs the synthesis of the relBE mRNA. High-resolution footprinting assays showed the distribution of bases whose deoxyriboses are protected by the bound proteins, demonstrating that RelB and RelB:RelE contacted the DNA backbone on one face of the DNA helix and that these interactions extended beyond the palindromic sequences. Our findings suggest that the binding of the RelBE proteins to its DNA target would lead to direct inhibition of the binding of the host RNA polymerase to the relBE promoter.

Download Full-text

Arthrospira platensis accelerates the formation of an endothelial cell monolayer and protects against endothelial cell detachment after bacterial contamination

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-201096 ◽

2021 ◽

pp. 1-11

Author(s):

A. Krüger-Genge ◽

S. Steinbrecht ◽

C.G.H. Jung ◽

Sophia Westphal ◽

Stefanie Klöpzig ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Bacterial Contamination ◽

Cell Monolayer ◽

Arthrospira Platensis ◽

Bacterial Toxin ◽

Cell Detachment ◽

Endothelial Cell Monolayer ◽

Positive Effects ◽

Anti Oxidant

Within the last years a comprehensive number of scientific studies demonstrated beneficial effect of Arthropira platensis (AP) as dietary supplement due to a high content of proteins, minerals and vitamins. Positive effects like promoting the immune system, reducing inflammation and an anti-oxidant capacity are reported. In this study, the effect of an aqueous AP extract on primary human venous endothelial cells (HUVEC) was investigated. In addition, the effect of AP on HUVEC treated with a bacterial toxin (lipopolysaccharide, LPA), inducing an activation of HUVEC and cellular detachment, was analyzed. Depending on the concentration of AP extract a significantly accelerated formation of an endothelial cell monolayer was observed. Furthermore, the detachment of HUVEC after LPA addition was dramatically reduced by AP. In conclusion, the data are promising and indicatory for an application of Arthrospira platensis in the clinical field.

Download Full-text

Bacterial toxin superantigens activate human T lymphocytes reactive with myelin autoantigens

Annals of Neurology ◽

10.1002/ana.410320308 ◽

1992 ◽

Vol 32 (3) ◽

pp. 352-357 ◽

Cited By ~ 15

Author(s):

James Burns ◽

Kim Littlefield ◽

Januaryice Gill ◽

John L. Trotter

Keyword(s):

T Lymphocytes ◽

Bacterial Toxin ◽

Human T Lymphocytes

Download Full-text

Down-Regulation of Annexin A1 in the Urothelium Decreases Cell Survival After Bacterial Toxin Exposure

The Journal of Urology ◽

10.1016/j.juro.2013.01.088 ◽

2013 ◽

Vol 190 (1) ◽

pp. 325-333 ◽

Cited By ~ 5

Author(s):

Katia Monastyrskaya ◽

Eduard B. Babiychuk ◽

Annette Draeger ◽

Fiona C. Burkhard

Keyword(s):

Cell Survival ◽

Bacterial Toxin ◽

Annexin A1 ◽

Down Regulation ◽

Toxin Exposure

Download Full-text