A5086145668- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Antimicrobial Resistance in Staphylococcus
- Bacteriophages and microbial interactions
- Enzyme Structure and Function
- Escherichia coli research studies
- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Bacterial biofilms and quorum sensing
- Biochemical and Structural Characterization
- Microbial Metabolism and Applications
- Microbial Natural Products and Biosynthesis
Boston VA Research Institute
2023-2025
Harvard University
2022-2025
City College of New York
2016-2021
The Graduate Center, CUNY
2016-2021
Abstract Staphylococcus aureus is a Gram-positive pathogen responsible for antibiotic-resistant infections. To identify vulnerabilities in cell envelope biogenesis that may overcome resistance, we enriched S. transposon mutants with defects surface integrity or division by sorting cells stain propidium iodide have increased light-scattering properties, respectively. Transposon sequencing of the sorted populations identified more than 20 previously uncharacterized factors impacting these...
Synthetic lethality occurs when inactivation of two genes is lethal but either single gene not. This phenomenon provides an opportunity for efficient compound discovery. Using differential growth screens, one can identify biologically active compounds that selectively inhibit proteins within the synthetic network any inactivated gene. Here, based purely on lethalities, we identified as only possible inhibitors Staphylococcus aureus lipoteichoic acid (LTA) biosynthesis from a screen ∼230,000...
Staphylococcus aureus is a Gram-positive pathogen responsible for numerous antibiotic-resistant infections. Identifying vulnerabilities in S. crucial developing new antibiotics to treat these With this mind, we probed the function of GdpS, conserved Staphylococcal membrane protein containing cytoplasmic GGDEF domain. These domains are canonically involved cyclic-di-GMP signaling processes, but not known make cyclic-di-GMP. Using transposon screen, found that loss GdpS lethal when combined...
Genome modification is essential for studying and engineering bacteria, yet making efficient modifications to most species remains challenging. Bacteriophage-encoded single-stranded DNA–annealing proteins (SSAPs) can facilitate genome editing by homologous recombination, but their typically narrow host range limits broad application. Here, we demonstrate that a single library of 227 SSAPs enables genome-editing across six diverse bacteria from three divergent classes: Actinomycetia (...
Polymerization of a ring-like cytoskeletal structure, the Z-ring, at midcell is highly conserved feature in virtually all bacteria. The Z-ring composed short protofilaments tubulin homolog FtsZ, randomly arranged and held together through lateral interactions. In vitro, associations between FtsZ are stabilized by crowding agents, high concentrations divalent cations, or some cases, low pH. vivo, last 4–10 amino acid residues C-terminus (the C-terminal variable region, CTV) have been...
The bacterial cytoplasmic membrane is a principal site of protein translocation, lipid and peptidoglycan biogenesis, signal transduction, transporters energy generating components the respiratory chain. Although 25-30% proteomes consist proteins, comprehensive understanding their influence on fundamental cellular processes incomplete. Here, we show that YciB DcrB, two small proteins previously unknown functions, play an essential synergistic role in maintaining cell envelope integrity...
SUMMARY Staphylococcus aureus is a gram-positive pathogen responsible for life-threatening infections that are difficult to treat due antibiotic resistance. The identification of new vulnerabilities in essential processes like cell envelope biogenesis represents promising avenue towards the development anti-staphylococcal therapies overcome To this end, we performed sorting-based enrichments S. mutants with defects integrity and division. We identified many known factors as well large...
Antibiotic resistance in bacterial pathogens is an ongoing public health concern. The arylomycins are a class of natural product antibiotics that target the type I signal peptidase, which carries out terminal step protein secretion. Here, we used transposon sequencing (Tn-Seq) to profile effects optimized arylomycin derivative G0775 Staphylococcus aureus. Our libraries include both upregulation and inactivation mutants, allowing us identify mechanisms targets for synergism. We identified...
A distinguishing feature of Gram-negative bacteria is their double-membraned cell envelope, which presents a formidable barrier against environmental stress. In E. coli , more than quarter the cellular proteins reside at inner membrane, but about third these are functionally unassigned or function incompletely understood.