A5040466202- Bacterial Genetics and Biotechnology
- Antimicrobial Resistance in Staphylococcus
- RNA and protein synthesis mechanisms
- Neurological diseases and metabolism
- Probiotics and Fermented Foods
- Pneumonia and Respiratory Infections
- RNA regulation and disease
- Antibiotic Resistance in Bacteria
- Metabolism and Genetic Disorders
- Gut microbiota and health
- Streptococcal Infections and Treatments
- Enzyme Catalysis and Immobilization
- Bacteriophages and microbial interactions
- Reproductive tract infections research
- Microbial Metabolic Engineering and Bioproduction
- Bacterial biofilms and quorum sensing
- Microbial Natural Products and Biosynthesis
- Enzyme Structure and Function
- Urinary Tract Infections Management
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and biosynthesis
- Antimicrobial agents and applications
- Hereditary Neurological Disorders
- Porphyrin Metabolism and Disorders
- Endoplasmic Reticulum Stress and Disease
St. Jude Children's Research Hospital
2015-2024
Donald & Barbara Zucker School of Medicine at Hofstra/Northwell
2019-2024
Ocean Medical Center
2024
University Medical Center
2024
Jersey Shore University Medical Center
2023
Hofstra University
2019
Mount Sinai Beth Israel
2016-2018
Icahn School of Medicine at Mount Sinai
2017-2018
North Carolina State University
2016
Xiaomi (China)
2015
An approach to global restriction mapping is described that applicable any complex source DNA. By analyzing a single digest for each member of redundant set lambda clones, data base constructed contains fragment-size lists all the clones. The clones are then grouped into subsets, which related at least one other by significant overlap. Finally, tree-searching algorithm seeks maps consistent with in subset. feasibility has been demonstrated collecting on 5000 containing random 15-kilobase...
Many bacterial species are represented by a pan-genome, whose genetic repertoire far outstrips that of any single genome. Here we investigate how pan-genome might influence gene essentiality and whether essential genes initially critical for the survival an organism can evolve to become non-essential. By using Transposon insertion sequencing (Tn-seq), whole-genome RNA-seq on set 36 clinical Streptococcus pneumoniae strains representative >68% species' identify species-wide 'essentialome' be...
A link exists between endoplasmic reticulum (ER) biogenesis and the unfolded protein response (UPR), a complex set of signaling mechanisms triggered by increased demands on folding capacity ER. The UPR transcriptional activator X-box binding 1 (XBP1) regulates expression proteins that function throughout secretory pathway is necessary for development an expansive ER network. We previously demonstrated overexpression XBP1(S), active form XBP1 generated UPR-mediated splicing Xbp1 mRNA,...
Development of the expansive endoplasmic reticulum (ER) present in specialized secretory cell types requires X-box-binding protein-1 (Xbp-1). Enforced expression XBP-1(S), a transcriptional activator generated by unfolded protein response-mediated splicing Xbp-1 mRNA, is sufficient to induce proliferation rough ER. We previously showed that XBP-1(S)-induced ER biogenesis fibroblasts correlates with increased production phosphatidylcholine (PtdCho), primary phospholipid membrane, and enhanced...
The rationale for the pursuit of bacterial type 2 fatty acid synthesis (FASII) as a target antibacterial drug discovery in Gram-positive organisms is being debated vigorously based on their ability to incorporate extracellular acids. regulation FASII by acids was examined Staphylococcus aureus and Streptococcus pneumoniae , representing two important groups pathogens. Both bacteria use same enzymatic tool kit conversion acyl-acyl carrier protein, elongation, incorporation into phospholipids....
The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward gram-positive bacteria. A screen of as growth inhibitors Staphylococcus aureus revealed structure-specific antibacterial activity. Fatty like oleate (18:1Δ9) were nontoxic, whereas palmitoleate (16:1Δ9) was a potent inhibitor. Cells treated with 16:1Δ9 exhibited rapid membrane depolarization, the disruption all major branches macromolecular synthesis, release solutes...
Summary Acyl‐ CoA and acyl‐acyl carrier protein ( ACP ) synthetases activate exogenous fatty acids for incorporation into phospholipids in G ram‐negative bacteria. However, Gram‐positive bacteria utilize an acyltransferase pathway the biogenesis of phosphatidic acid that begins with acylation sn ‐glycerol‐3‐phosphate by PlsY using acyl‐phosphate (acyl‐ PO 4 intermediate. PlsX generates acyl‐ from end‐products synthesis. The plsX gene S taphylococcus aureus was inactivated resulting strain...
ABSTRACT Serious bacterial infections in immunocompromised patients require highly effective antibacterial therapy for cure, and thus, this setting may reveal novel mechanisms by which bacteria circumvent antibiotics the absence of immune pressure. Here, an infant with leukemia developed vancomycin-resistant Enterococcus faecium (VRE) bacteremia that persisted 26 days despite appropriate antibiotic therapy. Sequencing 22 consecutive VRE isolates identified emergence a single missense...
Pantothenate kinase (PANK) is a metabolic enzyme that regulates cellular coenzyme A (CoA) levels. There are three human PANK genes, and inactivating mutations in PANK2 lead to pantothenate associated neurodegeneration (PKAN). Here we performed library screen followed by chemical optimization produce PZ-2891, an allosteric activator crosses the blood brain barrier. PZ-2891 occupies pocket engages dimer interface form PANK•ATP•Mg2+•PZ-2891 complex. The binding of one protomer locks opposite...
Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance Lactobacillus iners instead of crispatus, which has more beneficial associations. Strategies to L. crispatus and inhibit are thus needed. We show that oleic acid (OA) similar long-chain fatty acids simultaneously enhance growth. These...
The pneumococcus is one of the most prodigious producers hydrogen peroxide amongst bacterial pathogens. Hydrogen production by has been implicated in antibiotic synergism, competition between other colonizers nasopharynx, and damage to epithelial cells. However, role during invasive disease less clear with mutants defective demonstrating both attenuation heightened capacity depending upon strain serotype background. This work resolves these conflicting observations that main producing enzyme...
Detailed knowledge on how bacteria evade antibiotics and eventually develop resistance could open avenues for novel therapeutics diagnostics. It is thereby key to a comprehensive genome-wide understanding of process antibiotic stress, modulation the involved processes affects their ability overcome said stress. Here we undertake genetic analysis human pathogen Streptococcus pneumoniae responds 20 antibiotics. We build atlas drug susceptibility determinants generated interaction network that...
Stimulated B-lymphocytes differentiate into plasma cells committed to antibody production. Expansion of the endoplasmic reticulum and Golgi compartments is a prerequisite for high rate synthesis, assembly, secretion immunoglobulins. The bacterial cell wall component lipopolysaccharide (LPS) stimulates murine B-cells proliferate antibody-secreting that morphologically resemble cells. LPS activation CH12 augmented phospholipid production initiated genetic program, including elevated expression...
2,4-Dihydroxyquinoline (DHQ) is an abundant extracellular metabolite of the opportunistic pathogen Pseudomonas aeruginosa that secreted into growth medium in stationary phase to concentrations comparable with those quinolone signal. Using a combination biochemical and genetic approaches, we show PqsD, condensing enzyme pqs operon essential for signal synthesis, accounts DHQ formation vivo. First, anthraniloyl moiety transferred active-site Cys PqsD form anthraniloyl-PqsD intermediate, which...
Members of the Bacteroidetes phylum, represented by Alistipes finegoldii, are prominent anerobic, Gram-negative inhabitants gut microbiome. The lipid biosynthetic pathways were analyzed using bioinformatic analyses, lipidomics, metabolic labeling and biochemistry to characterize exogenous fatty acid metabolism. A. finegoldii only produced saturated acids. most abundant lipids phosphatidylethanolamine (PE) sulfonolipid (SL). Neither phosphatidylglycerol nor cardiolipin present. PE synthesis...
Oleate hydratases (OhyAs) belong to a large family of bacterial proteins catalyzing the hydration or isomerization double bonds in unsaturated fatty acids. A Staphylococcus aureus gene (Sa0102) is predicted encode an OhyA. Here, we recombinantly expressed and purified SaOhyA found that it forms homodimer requires FAD for activity. hydrates only acids containing cis-9 bonds, but not with trans-9 cis at other positions. products were detected S. phospholipids released into growth medium. does...
utilizes the fatty acid (FA) kinase system to activate exogenous FAs for membrane synthesis. We developed a lipidomics workflow determine phosphatidylglycerol (PG) molecular species synthesized by
Branched-chain amino acids (primarily isoleucine) are important regulators of virulence and converted to precursor molecules used initiate fatty acid synthesis in Staphylococcus aureus. Defining how bacteria control their membrane phospholipid composition is key understanding adaptation different environments. Here, we mass tracing experiments show that extracellular isoleucine preferentially metabolized by the branched-chain ketoacid dehydrogenase complex, contrast valine, which not...
Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated acids. These compounds are thought attenuate the immune response, but underlying signaling mechanism(s) remain be established. The pathogen Staphylococcus aureus also expresses an and 10-hydroxyoctadecanoic acid ( h 18:0) is most abundant metabolite found at Staphylococcal skin infection sites. Here, we show 18:0 stimulates transcription set lipid metabolism genes...
Pantothenate is the precursor of essential cofactor coenzyme A (CoA). kinase (CoaA) catalyzes first and regulatory step in CoA biosynthetic pathway. The pantothenate analogs N-pentylpantothenamide N-heptylpantothenamide possess antibiotic activity against Escherichia coli. Both compounds are substrates for E. coli CoaA competitively inhibit phosphorylation pantothenate. phosphorylated pantothenamides further converted to analogs, which were previously predicted act as inhibitors...
The obligate intracellular parasite Chlamydia trachomatis has a reduced genome and is thought to rely on its mammalian host cell for nutrients. Although several lines of evidence suggest C. utilizes phospholipids, the bacterium encodes all genes necessary fatty acid phospholipid synthesis found in free living Gram-negative bacteria. Bacterially derived phospholipids significantly increased infected HeLa cultures. These new had distinct molecular species composition consisting saturated...