A5079799850- Biochemical and Structural Characterization
- Tuberculosis Research and Epidemiology
- Bacterial Genetics and Biotechnology
- Botanical Research and Chemistry
- Mycobacterium research and diagnosis
- Streptococcal Infections and Treatments
- HIV Research and Treatment
- Autophagy in Disease and Therapy
- Bacterial biofilms and quorum sensing
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune cells in cancer
- Bacteriophages and microbial interactions
- Enzyme Production and Characterization
- Antimicrobial Peptides and Activities
- Bacillus and Francisella bacterial research
- interferon and immune responses
- RNA Interference and Gene Delivery
- Protein Hydrolysis and Bioactive Peptides
- CRISPR and Genetic Engineering
- Cardiac Ischemia and Reperfusion
- Machine Learning in Bioinformatics
- Anorectal Disease Treatments and Outcomes
- Drug-Induced Adverse Reactions
- Cannabis and Cannabinoid Research
- Vibrio bacteria research studies
University of California System
2024
University of California, San Francisco
2014-2024
University of California, Berkeley
2019-2024
Universidad Católica de Santa Fe
2023
Berkeley College
2020
University of Oxford
2006-2013
University of Chicago
2006-2012
Dartmouth College
2002-2004
Mycobacterium tuberculosis (Mtb) infects lung myeloid cells, but the specific Mtb-permissive cells and host mechanisms supporting Mtb persistence during chronic infection are incompletely characterized. We report that after development of T cell responses, CD11c lo monocyte-derived harbor more live than alveolar macrophages (AM), neutrophils, hi cells. Transcriptomic functional studies revealed lysosome pathway is underexpressed in this highly permissive subset, characterized by less...
Macrophages are highly plastic cells with critical roles in immunity, cancer, and tissue homeostasis, but how these distinct cellular fates triggered by environmental cues is poorly understood. To uncover primary murine macrophages respond to bacterial pathogens, we globally assessed changes post-translational modifications of proteins during infection
Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but myeloid-lineage have remained largely genetically intractable. We present a method for the delivery ribonucleoprotein (RNP) complexes by nucleofection directly into CD14+ monocytes purified from peripheral blood, leading high rates precise gene knockout. These can be efficiently differentiated monocyte-derived macrophages or dendritic cells. This process...
A temperate, type IV pilus-dependent, double-stranded DNA bacteriophage named DMS3 was isolated from a clinical strain of Pseudomonas aeruginosa. clear-plaque variant this isolated. is capable mediating generalized transduction within and between P. aeruginosa strains PA14 PAO1, thus providing useful tool for the genetic analysis
Summary Vegetative forms of Bacillus cereus are reported to form pili, thin protein filaments that protrude up 1 μm from the bacterial surface. Pili assembled two precursor proteins, BcpA and BcpB, in a manner requiring pilus‐associated sortase enzyme (SrtD). also formed on surface anthracis expressing bcpA ‐ srtD bcpB . is distributed throughout entire pilus, whereas BcpB appears positioned at its tip. In agreement with hypothesis for pilus assembly Gram‐positive bacteria, encompasses YPK...
Pilin precursors are the building blocks of pili on surface Gram-positive bacteria; however, assembly mechanisms these adhesive fibers unknown. Here, we describe chemical bonds that assemble BcpA pilin subunits Bacillus cereus. Sortase D cleaves precursor between threonine (T) and glycine (G) residues its LPXTG sorting signal catalyzes formation an amide bond lysine (K) in YPKN motif another subunit. Three CNA B domains generate intramolecular bonds, one contributes also to pilus formation....
Summary Bacillus cereus G9241 causes an anthrax‐like respiratory illness in humans; however, the molecular mechanisms of disease pathogenesis are not known. Genome sequencing identified two putative virulence plasmids proposed to provide for anthrax toxin (pBCXO1) and/or capsule expression (pBC218). We report here that B. immune‐competent mice, which is dependent on each plasmids. pBCXO1 encodes pagA1 , homologue protective antigen, as well hasACB providing hyaluronic acid formation, traits...
Gram-positive bacteria elaborate pili and do so without the participation of folding chaperones or disulfide bond catalysts. Sortases, enzymes that cut pilin precursors, form covalent bonds link subunits assemble on bacterial surface. We determined x-ray structure BcpA, major subunit Bacillus cereus. The BcpA precursor encompasses 2 Ig folds (CNA(2) CNA(3)) one jelly-roll domain (XNA) each which synthesizes a single intramolecular amide bond. A fourth bond, derived from fold CNA(1), is...
The development of novel antibiotics is essential because the current arsenal antimicrobials will soon be ineffective due to widespread occurrence antibiotic resistance. naturally occurring cationic antimicrobial peptides (CAMPs) for therapeutics combat resistance has been hampered by high production costs and protease sensitivity, among other factors.
Bacillus anthracis, the causative agent of anthrax, is a dangerous biological weapon, as spores derived from drug-resistant strains cause infections for which antibiotic therapy no longer effective. We sought to develop an anti-infective anthrax and targeted CapD, enzyme that cleaves poly-gamma-D-glutamate capsule generates amide bonds with peptidoglycan cross-bridges deposit capsular material into envelope B. anthracis. In agreement model confers protection phagocytic clearance, anthracis...
Assembly of pili in Gram-positive bacteria and their attachment to the cell wall envelope are mediated by sortases. In Bacillus cereus its close relative anthracis, major pilin protein BcpA is cleaved between threonine glycine C-terminal LPXTG motif sorting signal pilin-specific sortase D. The resulting acyl enzyme intermediate relieved nucleophilic attack side-chain amino group lysine within YPKN another subunit. Cell anchoring assembled requires A, which also cleaves residues. We show here...
Bacillus cereus and other Gram-positive bacteria elaborate pili via a sortase D-catalyzed transpeptidation mechanism from major minor pilin precursor substrates. After cleavage of the LPXTG sorting signal pilin, BcpA, D forms an amide bond between C-terminal threonine amino group lysine within YPKN motif another BcpA subunit. Pilus assembly terminates upon A signal, resulting in covalent cell wall cross-bridge. Here, we show that IPNTG BcpB, is cleaved by but not A. The BcpB amide-linked to...
Background Pyrazinamide (PZA) is a first line agent for the treatment of active tuberculosis. PZA also considered potent companion drug newer regimens under development. There are limited data on demographic, clinical, and pathogen characteristics resistant Methods Using retrospective cohort study design, we evaluated all M. tuberculosis (M.tb) bovis cases reported in San Francisco from 1991 to 2011. Demographic, molecular were analyzed. M.tb lineage was determined strains compared...
Bacillus cereus strains elaborate pili on their surface using a mechanism of sortase-mediated cross-linking major and minor pilus components. Here we used combination electron microscopy atomic force to visualize these structures. Pili occur as single, double or higher order assemblies filaments formed from monomers the pilin, BcpA, capped by BcpB. Previous studies demonstrated that within assembled pili, four domains BcpA - CNA(1), CNA(2), XNA CNA(3) each acquire intramolecular...
Vascular endothelial growth factor (VEGF) is an cell mitogen responsible for physiological and pathological angiogenesis. Abnormal regulation of VEGF expression in anterior pituitary folliculostellate (FS) cells has been implicated tumour progression. FS endocrine express VEGF, which considered to be secreted by the constitutive pathway. The present study investigated mechanism secretion TtT/GF cells, a mouse line. were shown VEGF(164), most potent bioavailable isoform VEGF....
<title>Abstract</title> <italic>Mycobacterium tuberculosis</italic> (Mtb) persists in lung myeloid cells during chronic infection. However, the mechanisms allowing Mtb to evade elimination are not fully understood. Here, we determined that phase, CD11c<sup>lo</sup> monocyte-derived termed MNC1 (mononuclear cell subset 1), harbor more live than alveolar macrophages (AM), neutrophils, and less permissive CD11c<sup>hi</sup> MNC2. Transcriptomic functional studies of sorted revealed lysosome...
SUMMARY Macrophages activate robust antimicrobial functions upon engulfing virulent bacteria, yet a wide array of pathogens paradoxically thrive within these innate immune cells. To probe the pathogen-macrophage interface, we used proteomics to comprehensively quantify changes in post-translational modifications (PTMs) host proteins during infection with three evolutionarily diverse intracellular pathogens: Mycobacterium tuberculosis, Salmonella enterica serovar Typhimurium, and Listeria...
Summary Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but myeloid-lineage have remained largely genetically intractable. We present a method for delivery ribonucleoprotein (RNP) complexes by nucleofection directly into CD14+ monocytes purified from peripheral blood, leading high rates precise gene knockout. These can be efficiently differentiated monocyte-derived macrophages or dendritic cells. This...