A5057377059- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Bacterial biofilms and quorum sensing
- Vibrio bacteria research studies
- Antibiotic Resistance in Bacteria
- Bacillus and Francisella bacterial research
- Streptococcal Infections and Treatments
- Yersinia bacterium, plague, ectoparasites research
- Neonatal and Maternal Infections
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Protein Structure and Dynamics
- Antimicrobial Resistance in Staphylococcus
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Advanced biosensing and bioanalysis techniques
- Escherichia coli research studies
- Antimicrobial Peptides and Activities
- Cystic Fibrosis Research Advances
- Biotin and Related Studies
- Mast cells and histamine
- Microbial Inactivation Methods
Harvard University
2014-2023
Boston Children's Hospital
2014-2023
University of Rhode Island
2021
Florida International University
2013
National University of Singapore
2012
In-Q-Tel
2008
Massachusetts General Hospital
2000-2005
Harvard University Press
2002
National Academy of Medicine
2000
Trinity College Dublin
1996-1997
Type III secretion systems are toxin delivery that present in a large number of pathogens. A hallmark all type studied to date is expression one or more their components induced upon cell contact. It has been proposed this induction controlled by negative regulator itself secreted means the machinery. Although candidate proteins for have systems, most part, direct demonstration role regulation lacking. Here, we report discovery ExsE, gene Pseudomonas aeruginosa . Deletion exsE deregulates...
We report here the results of an analysis regulatory range GacS/GacA two-component system in Pseudomonas aeruginosa. Using microarrays, we identified a large number genes that are regulated by system, and detected near complete overlap these with those two small RNAs (sRNAs), RsmY RsmZ, suggesting expression all GacA-regulated is RsmY/Z-dependent. genome-wide DNA-protein interaction analyses, only genomic regions associated specifically GacA, located upstream rsmY rsmZ genes. These...
Transcription of the agn43 locus, which specifies an outer membrane protein Escherichia coli, is regulated in a phase-variable fashion by OxyR-DNA binding and Dam methylase. Despite its well-characterized regulation, function Ag43 has remained elusive until now. Previous studies indicated that mediates autoaggregation certain strains E. coli liquid culture. Given this phenotype, we examined role biofilm formation. Here, report contributes to formation glucose-minimal medium, but not...
The tubulin-like FtsZ protein initiates assembly of the bacterial cytokinetic machinery by polymerizing into a ring structure, Z ring, at prospective site division. To block Z-ring formation over nucleoid and help coordinate cell division with chromosome segregation, Escherichia coli employs nucleoid-associated inhibitor, SlmA. Here, we investigate mechanism which SlmA regulates assembly. We show that disassembles polymers in vitro. In addition, using chromatin immunoprecipitation (ChIP),...
The histone-like nucleoid structuring protein, H-NS, is a prominent global regulator of gene expression. Many Gram-negative bacteria contain multiple members the H-NS family proteins. Thus, key question whether have overlapping or distinct functions. To address this we performed genome-wide location analyses with MvaT and MvaU, two present in Pseudomonas aeruginosa. We show that MvaU bind same chromosomal regions, coregulating expression approximately 350 target genes. further like enteric...
In bacteria, promoter recognition depends on the RNA polymerase σ subunit, which combines with catalytically proficient core to form holoenzyme. The major class of bacterial promoters is defined by two conserved elements (the –10 and –35 elements, are 10 35 nucleotides upstream initiation point, respectively) that contacted in We show this “flexible flap” domain β subunit. flap interacts region 4 triggers a conformational change moves into correct position for interaction element. Because...
Simon L. Dove and Ann Hochschild Department of Microbiology Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115 USA
Hfq is an RNA chaperone and important post-transcriptional regulator in bacteria. Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq), we show that associates hundreds of different regions the Pseudomonas aeruginosa chromosome. These associations are abolished when transcription inhibited, indicating they reflect binding to transcripts during their synthesis. Analogous ChIP-seq analyses Crc reveal it many same nascent as Hfq, activity dependent. Our...
The RNA chaperone Hfq plays important regulatory roles in many bacteria by facilitating the base pairing between small RNAs (sRNAs) and their cognate mRNA targets. In gram-negative opportunistic pathogen Pseudomonas aeruginosa, over a hundred putative sRNAs have been identified but for most, targets remained unknown. Using RIL-seq with P. we dozens of previously known unknown sRNAs. Strikingly, hundreds RNA-RNA interactions discovered involved PhrS. This sRNA was thought to mediate its...
The cupA gene cluster of Pseudomonas aeruginosa encodes components a putative fimbrial structure that enable this opportunistic human pathogen to form biofilms on abiotic surfaces. In P. , expression is repressed by MvaT, transcription regulator thought belong the H-NS family nucleoid-associated proteins typically function repressing transcription. Here, we present evidence MvaT controls phase-variable (ON/OFF) cluster. Using directed proteomic approach, show associates with related protein...
Phenotypic variation within an isogenic bacterial population is thought to ensure the survival of a subset cells in adverse conditions. The opportunistic pathogen Pseudomonas aeruginosa variably expresses several phenotypes, including antibiotic resistance, biofilm formation, and production CupA fimbriae. Here we describe previously unidentified bistable switch P. aeruginosa. This controls expression diverse set genes, aprA, which encodes secreted virulence factor alkaline protease. We...
H-NS is an abundant DNA-binding protein that has been implicated in the silencing of foreign DNA several different bacteria. The ability dimers to form higher-order oligomers thought aid polymerization across AT-rich stretches and facilitate gene silencing. Although oligomerization from enteric bacteria subject intense investigation, little known regarding family members outside enterobacteriaceae, many which share sequence similarity with their counterparts. Here we show MvaT, a member...
Members of the histone-like nucleoid-structuring (H-NS) family proteins have been shown to play important roles in silencing gene expression and nucleoid compaction. In Pseudomonas aeruginosa, two H-NS members MvaT MvaU are thought bind same AT-rich regions chromosome function coordinately control a common set genes. Here we present evidence that loss both cannot be tolerated because it results production Pf4 phage superinfect kill cells or inhibit their growth. Using ClpXP-based protein...
The type VI secretion system (T6SS) has emerged as an important mediator of interbacterial interactions. A T6SS from Pseudomonas aeruginosa targets at least three effector proteins, exported 1–3 (Tse1–3), to recipient Gram-negative cells. Tse2 protein is a cytoplasmic that acts potent inhibitor target cell proliferation, thus providing pronounced fitness advantage for P. donor utilizes dedicated immunity protein, 2 (Tsi2), protect against endogenous and intercellularly-transferred Tse2. Here...
Pseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ΔplcHR mutant, known to be defective virulence animal models, was less able colonize epithelial monolayers biofilm formation on plastic when grown Microarray analyses found that strains PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated Anr regulon Anr-dependent manner under conditions...
Bacterial xenogeneic silencing proteins selectively bind to and silence expression from many AT rich regions of the chromosome. They serve as master regulators horizontally acquired DNA, including a large number virulence genes. To date, three distinct families silencers have been identified: H-NS Proteobacteria, Lsr2 Actinomycetes, MvaT Pseudomonas sp. Although family are structurally different, they all recognize AT-rich DNA minor groove through common AT-hook-like motif, which is absent...
Pathogenicity of Pseudomonas aeruginosa, a major cause many acute and chronic human infections, is determined by tightly regulated expression multiple virulence factors. Quorum sensing (QS) controls these pathogenic determinants. Previous microarray studies have shown that the AmpC β-lactamase regulator AmpR, member LysR family transcription factors, also non-β-lactam resistance mechanisms. Using RNA-Seq complementary assays, this study further expands AmpR regulon to include diverse...
Significance The programmed cell death (PCD) of mammalian cells plays important roles in fighting bacterial infections. Relatively little is known about the adaptive role PCD bacteria. Here we report discovery a potential pathway Pseudomonas aeruginosa . We show that activation system can occur subset response to DNA damage through cleavage an essential transcription regulator controls lysis program. Although this lethal individual which it occurs, find enhances ability bacterium cause...
In the opportunistic pathogen Pseudomonas aeruginosa , RsmA is an RNA-binding protein that plays critical roles in control of virulence, interbacterial interactions, and biofilm formation. Although thought to exert its regulatory effects by binding full-length transcripts, extent which binds nascent transcripts has not been addressed. Moreover, are direct targets this key posttranscriptional regulator largely unknown. Using chromatin immunoprecipitation coupled with high-throughput DNA...