Interactions of the effector ExoU from Pseudomonas aeruginosa with short-chain phosphatidylinositides provide insights into ExoU targeting to host membranes Molecular Biophysics

In this study, we used site-directed spin-labeling electron paramagnetic resonance spectroscopy to examine the interaction of ExoU with soluble analogs of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). We found that dioctanoyl PI(4,5)P2 binds to and induces conformational changes in a C-terminal four-helix bundle (4HB) domain of ExoU implicated previously in membrane binding. Other soluble phosphoinositides also interacted with the 4HB but less effectively. Molecular modeling and ligand docking studies indicated the potential for numerous hydrogen bond interactions within and between interhelical loops of the 4HB and suggested several potential interaction sites for PI(4,5)P2. Site-directed mutagenesis experiments confirmed that the side chains of Gln-623 and Arg-661 play important roles in mediating PI(4,5)P2-induced conformational changes in ExoU. These results support a mechanism in which direct interactions with phosphatidylinositol-containing lipids play an essential role in targeting ExoU to host membrane bilayers. Molecules or peptides that block this interaction may prove useful in preventing the cytotoxic effects of ExoU to mitigate the virulence of P. aeruginosa strains that express this potent phospholipase toxin.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Membrane Biology Source Type: research

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In this study we have genetically modified a serotype 1 strain (519/43), the first time that this has been achieved for this serotype, providing the methodology for a deeper understanding of its biology and pathogenicity. As proof of principle we constructed a defined pneumolysin mutant and showed that it lost its ability to lyse red blood cells. We also showed that when mice were infected intranasally with the mutant 519/43Δply there was no significant difference between the load of bacteria in lungs and blood when compared to the wild type 519/43. When mice were infected intraperitoneally there were significantly f...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
This study represents the first large scale attempt to gather a long period information on Q fever infection in Greece. The findings of the current study support the fact that Q fever is an important endemic zoonotic disease in Greece and needs increased awareness by clinical physicians and health care system.
Source: Comparative Immunology, Microbiology and Infectious Diseases - Category: Infectious Diseases Source Type: research
ConclusionP. karwinskii leaf extract inhibited reactive oxygen species and exerted an anti-inflammatory effect. Moreover, this extract did not induce gastric damage in the animals. The bioactivity of the species was found to support its traditional use in traditional medicine. This orchid could be used to treat inflammatory diseases without causing the side effects associated with Nonsteroidal anti-inflammatory drugs. It can also be employed to treat other pathological conditions associated with oxidative stress. The findings herein form the basis for the future discovery of natural products that may serve as safe alternat...
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 25 January 2020Source: BurnsAuthor(s): BÅ™etislav Lipový, Serhiy Forostyak
Source: Burns - Category: Dermatology Source Type: research
(LOS ANGELES) — The U.S. has five confirmed cases of the new virus from China, all among people who traveled to the city at the center of the outbreak, health officials said Sunday. Two new cases were reported Sunday — one in Los Angeles County in California and the other in Maricopa County, Arizona. The latter case was someone with ties to Arizona State University who did not live in school housing, state health officials said. The three previously reported cases were a patient in Orange County, California; a man in his 30s in Washington state; and a woman in her 60s from Chicago. The virus can cause fever, c...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized California onetime Virus Source Type: news
This study presents a combined dielectrophoresis (DEP) - Raman Spectroscopy (RS) method to obtain direct, real-time measurements of the susceptibility of a suspension of planktonic bacteria without labelling or other time-consuming and intrusive sample preparation processes. Using an in-house constructed DEP-Raman device, we demonstrated the susceptibility of Escherichia coli MG1655 towards the second-generation fluoroquinolone antibiotic ciprofloxacin (CP) after only 1 h of treatment, by monitoring spectral changes in the chemical fingerprint of bacteria related to the mode of action of the drug. Spectral variance ...
Source: Sensors and Actuators B: Chemical - Category: Chemistry Source Type: research
The Skeptics Annotated Bible introduction to Leviticus begins, " I wouldn't read Leviticus if I were you. No one else does. " That's probably good advice, but we're committed to this project so off we go. One of the key reasons I'm doing this is to prove that people who claim that the Bible is the literal, inerrant word of God a) must have a very low opinion of God and b) don't pay any attention to 99% of what he says.Leviticus begins with detailed, specific instructions for dismembering and burning animals. And that is a good percentage of the entire book, actually, along with several other categories of bizarre...
Source: Stayin' Alive - Category: American Health Source Type: blogs
Publication date: Available online 25 January 2020Source: The American Journal of SurgeryAuthor(s): Sharven Taghavi, Glenn Jones, Juan Duchesne, Patrick McGrew, Chrissy Guidry, Rebecca Schroll, Charles Harris, Reginald Nkansah, Tomas Jacome, Danielle TatumAbstractBackgroundThe association of procedure volume and improved outcomes has been established with infrequently performed elective operations. However, effect of trauma center volume on outcomes in emergency surgery has not been defined. We hypothesized that high volume centers (HVC) would provide better outcomes for operative major vascular injuries (MVI) than low vol...
Source: The American Journal of Surgery - Category: Surgery Source Type: research
Coronavirus expert Ralph Baric joins TWiV to explain the virology and epidemiology of the recent zoonotic outbreak spreading across China and overseas. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove,Rich Condit, Kathy Spindler Guest: Ralph Baric Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode ASV 2020 WHO coronavirus sitreps CIDRAP article on coronavirus vaccines Phylogenetic analysis of 2019-nCoV ACE2 is 2019-nCoV receptor (bioRxiv) Visual explainer of Huanan market (SCMP) Clinical features of 2019-nCoV patients (Lancet...
Source: This Week in Virology - MP3 Edition - Category: Virology Authors: Source Type: podcasts
Publication date: Available online 25 January 2020Source: Journal of OrthopaedicsAuthor(s): Alex Gu, Frank R. Chen, Aaron Z. Chen, Safa C. Fassihi, Savyasachi Thakkar, Anthony S. Unger, Jiabin Liu, Peter K. Sculco, P. MichaelAbstractIntroductionThe purpose of this study is to investigate the relationship between preoperative hyponatremia and postoperative complications in aseptic revision hip and knee arthroplasty.MethodsAseptic revision arthroplasties from 2007-2016 were collected using a large, United States database. Patients were stratified into eunatremic and hyponatremic cohorts. Rates of complications were collected...
Source: Journal of Orthopaedics - Category: Orthopaedics Source Type: research
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