A5033180219- Vibrio bacteria research studies
- Antibiotic Resistance in Bacteria
- Escherichia coli research studies
- COVID-19 Clinical Research Studies
- Bacterial biofilms and quorum sensing
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Immune Response and Inflammation
- Bacterial Genetics and Biotechnology
- Neonatal Respiratory Health Research
- Inflammasome and immune disorders
- Yersinia bacterium, plague, ectoparasites research
- Cancer Research and Treatments
- Artificial Intelligence in Law
- Inhalation and Respiratory Drug Delivery
- Viral gastroenteritis research and epidemiology
- Genomics and Phylogenetic Studies
- Immune responses and vaccinations
- Bacteriophages and microbial interactions
- Natural Language Processing Techniques
- Topic Modeling
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Extracellular vesicles in disease
Massachusetts General Hospital
2019-2023
Foundation for the Advancement of Social Theory
2023
Boston VA Research Institute
2019-2022
Harvard University
2019-2022
Imperial College London
2015-2021
Mechanisms underlying severe coronavirus disease 2019 (COVID-19) remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune non-immune linked to COVID-19. Deconvolution of our proteome data using published scRNA-seq datasets reveals contributions from circulating tissue cells. Sixteen percent display reduced inflammation yet comparably poor outcomes. Comparison who died severely ill survivors...
Significance Bacteria evolved molecular weapons to help them thrive in polymicrobial environments. The type VI secretion system (T6SS) is a gun loaded with great diversity of bacterial toxins. On contact neighboring cells, toxins are fired, and the absence immunity, prey killed, allowing attacker prevail. Each bacterium can be equipped several distinct T6SSs, it unclear whether they simultaneously active or each has specific role particular environment. Here we showed that production three...
The type VI secretion system (T6SS) is crucial in interbacterial competition and a virulence determinant of many Gram-negative bacteria. Several T6SS effectors are covalently fused to secreted structural components such as the VgrG spike for delivery into target cells. In Pseudomonas aeruginosa, VgrG2b effector was previously proposed mediate bacterial internalization eukaryotic this work, we find that C-terminal domain (VgrG2bC-ter) elicits toxicity periplasm, counteracted by cognate...
Endotoxin-bacterial lipopolysaccharide (LPS)-is a driver of lethal infection sepsis through excessive activation innate immune responses. When delivered to the cytosol macrophages, cytosolic LPS (cLPS) induces assembly an inflammasome that contains caspases-4/5 in humans or caspase-11 mice. Whereas all other inflammasomes is triggered by sensing pathogen products specific host pattern recognition receptor protein, whether receptors for cLPS exist has remained unclear, because caspase-4,...
The bacterial pathogen Pseudomonas aeruginosa uses three type VI secretion systems (T6SSs) to drive a multitude of effector proteins into eukaryotic or prokaryotic target cells. T6SS is supramolecular nanomachine, involving set 13 core proteins, which resembles the contractile tail bacteriophages and whose tip considered as puncturing device helping cross membranes. Effectors can attach directly spike composed VgrG (valine-glycine-rich proteins) trimer, P. produces several. We have...
Bacteria exist in polymicrobial environments and compete to prevail a niche. The type VI secretion system (T6SS) is nanomachine employed by Gram-negative bacteria deliver effector proteins into target cells. Consequently, T6SS-positive produce wealth of antibacterial promote their survival among prokaryotic community. These toxins are loaded onto the VgrG-PAAR spike Hcp tube T6SS apparatus recent work has started document specificity effectors for certain components. Pseudomonas aeruginosa...
Summary COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 patients and 78 symptomatic controls serial timepoints using two complementary approaches, we uncover host immune non-immune not previously linked to this disease. Integration of proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage,...
Abstract Bacterial pathogens often subvert the innate immune system to establish a successful infection. The direct inhibition of downstream components pathways is particularly well documented but how bacteria interfere with receptor proximal events far less understood. Here, we describe Toll/interleukin 1 ( TIR ) domain‐containing protein (PumA) multi‐drug resistant Pseudomonas aeruginosa PA 7 strain. We found that PumA essential for virulence and inhibits NF ‐κB, property transferable...
During infection, some bacterial pathogens invade the eukaryotic cytosol and spread between cells of an epithelial monolayer. Intercellular occurs when these push against plasma membrane, forming protrusions that are engulfed by adjacent cells. Here, we show IpaC, a Shigella flexneri type 3 secretion system protein, binds host cell-adhesion protein β-catenin facilitates efficient protrusion formation. S. producing point mutant IpaC cannot interact with is defective in formation spread....
Pseudomonas aeruginosa uses three type six secretion systems (H1-, H2- and H3-T6SS) to manipulate its environment, subvert host cells for microbial competition. These T6SS machines are loaded with a variety of effectors/toxins, many being associated specific VgrG. How P. transcriptionally coordinates the main clusters multiple vgrG islands spread through genome is unknown. Here we show an unprecedented level control RsmA repressing most known T6SS-related genes. Moreover, each H3-T6SS...
Shigella spp. are important human pathogens and among the leading causes of diarrheal mortality worldwide, especially in children. Virulence depends on type III secretion system (T3SS).
Abstract Endotoxin - bacterial lipopolysaccharide (LPS) is a driver of the lethal infection sepsis through activation innate immune responses. When delivered to cytosol macrophages, LPS (cLPS) induces assembly an inflammasome that contains caspases-4/5 in humans or caspase-11 mice. Whereas all other inflammasomes triggered by sensing pathogen products specific host cytosolic pattern recognition receptor protein, whether receptors for cLPS exist has been doubted many investigators, as...
Abstract The type III secretion system is required for virulence of many pathogenic bacteria. Bacterial effector proteins delivered into target host cells by this modulate signaling pathways and processes in a manner that promotes infection. Here, we define the activity protein OspB human pathogen Shigella spp., etiological agent shigellosis dysenteric disease. Using yeast Saccharomyces cerevisiae as model organism, show sensitizes to inhibition TORC1, central regulator growth metabolism. In...