- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- Burkholderia infections and melioidosis
- Vibrio bacteria research studies
- Antibiotic Resistance in Bacteria
- Microbial Metabolism and Applications
- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- RNA and protein synthesis mechanisms
- Cystic Fibrosis Research Advances
- Medicinal Plants and Neuroprotection
- Biocrusts and Microbial Ecology
- Antimicrobial Peptides and Activities
- Bacteriophages and microbial interactions
- Gut microbiota and health
- Plant biochemistry and biosynthesis
- Plant Pathogenic Bacteria Studies
- Circadian rhythm and melatonin
- Probiotics and Fermented Foods
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Iron Metabolism and Disorders
- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Microbial Community Ecology and Physiology
University of Kansas
2016-2025
Stowers Institute for Medical Research
2022
University of Washington
2007-2016
Harvard University
2010-2011
J. Craig Venter Institute
2009
University of Minnesota
2004-2007
University of Minnesota Medical Center
2006
Kansas State University
2005
VIR Biotechnology (United States)
2005
ABSTRACT The genome of Burkholderia thailandensis codes for several LuxR-LuxI quorum-sensing systems. We used B. deletion mutants and recombinant Escherichia coli to determine the nature signals produced by one systems, BtaR2-BtaI2, show that this system controls genes required synthesis an antibiotic. BtaI2 is acyl-homoserine lactone (acyl-HSL) synthase produces two hydroxylated acyl-HSLs, N -3-hydroxy-decanoyl-HSL (3OHC 10 -HSL) -3-hydroxy-octanoyl-HSL 8 -HSL). btaI2 gene positively...
Acyl-homoserine lactone-mediated quorum sensing (QS) regulates diverse activities in many species of Proteobacteria. QS-controlled genes commonly code for production secreted or excreted public goods. The acyl-homoserine lactones are synthesized by members the LuxI signal synthase family and detected cognate LuxR transcriptional regulators. QS affords a means population density-dependent gene regulation. Control goods via provides fitness benefit. Another potential role is to anticipate...
Cystic fibrosis lung disease is characterized by chronic airway infections with the opportunistic pathogen Pseudomonas aeruginosa and severe neutrophilic pulmonary inflammation. P. undergoes extensive genetic adaptation to cystic (CF) environment, adaptive mutations in quorum sensing regulator gene lasR commonly arise. We sought define how alter host-pathogen relationships. demonstrate that mutants induce exaggerated host inflammatory responses respiratory epithelial cells, increased...
ABSTRACT Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway mediated by diffusible N -acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors Gram-negative bacteria. As many common pathogenic use QS regulate virulence, there significant interest disrupting as potential therapeutic strategy. Prior studies have implicated the natural...
ABSTRACT In the opportunistic pathogen Pseudomonas aeruginosa , nitrogen-related phosphotransferase system (PTS Ntr ) influences multiple virulence behaviors. The PTS is comprised of three enzymes: first PtsP, then PtsO phosphocarrier, and final PtsN phosphoacceptor. We previously showed that ptsP inactivation increases LasI-LasR quorum sensing, a by which P. regulates genes in response to population density. LasI synthesizes diffusible autoinducer binds activates LasR receptor, feedback...
Bacterial acyl-homoserine lactones upregulated an uncharacterized gene cluster (bta) in Burkholderia thailandensis E264 to produce polar antibiotic. The antibiotic is identified as a mixture of four bactobolins. Annotation the bta allows us propose biosynthetic scheme for bactobolin and reveals unusual enzymatic reactions further study.
Acyl-homoserine lactone (acyl-HSL) quorum-sensing signaling is common to many Proteobacteria. Acyl-HSLs are synthesized by the LuxI family of synthases, and signal response mediated members LuxR transcriptional regulators. Burkholderia thailandensis a member closely related cluster three species, including animal pathogens mallei pseudomallei. Members this group have similar luxI luxR homologs, these genes contribute B. pseudomallei virulence. possesses pairs luxI-luxR homologs. One pairs,...
ABSTRACT Many species of bacteria use a cell-cell communication system called quorum sensing (QS) to coordinate group activities. QS systems frequently regulate the production exoproducts. Some these products, such as proteases, are “public goods” that shared among population and vulnerable cheating by nonproducing members population. Because opportunistic pathogen Pseudomonas aeruginosa regulates several public goods, it can serve model for studying cooperation. Bacteria also commonly...
The ribosome is the target of a large number antibiotics. Here, we report 3.4-Å-resolution crystal structure bactobolin A bound to 70S ribosome-tRNA complex. antibiotic binds at previously unseen site in 50S subunit and displaces tRNA P-site. It thus likely has similar mechanism action as blasticidin S despite binding different site. also rationalizes identified resistance mutations.
Iron is an essential nutrient for bacteria but the reactivity of Fe2+ and insolubility Fe3+ present significant challenges to bacterial cells. storage proteins contribute ameliorating these by oxidizing using O2 H2O2 as electron acceptors, compartmentalizing Fe3+. Two types iron-storage coexist in bacteria, ferritins (Ftn) heme-containing bacterioferritins (Bfr), reasons their coexistence are largely unknown. P. aeruginosa cells harbor two iron (FtnA BfrB), nothing known about relative...
Members of the genus Burkholderia are known to be adept at biofilm formation, which presumably assists in survival these organisms environment and host. Biofilm formation has been linked quorum sensing (QS) several bacterial species. In this study, we characterized thailandensis development under flow conditions sought determine whether QS contributes process. B. exhibited an unusual pattern: cells formed small aggregates then proceeded produce mature biofilms by "dome" structures filled...
Conjugative transfer of the Enterococcus faecalis plasmid pCF10 is induced by peptide pheromone cCF10 when recipient-produced detected donors. produced proteolytic processing signal sequence a chromosomally encoded lipoprotein (CcfA). In donors, endogenously carefully controlled to prevent constitutive expression conjugation functions, an energetically wasteful process, except in vivo, where endogenous induces conjugation-linked virulence factor. Endogenous two plasmid-encoded products;...
Although iron is essential for bacteria, the nutrient presents problems of toxicity and solubility. Bacteria circumvent these with aid storage proteins where Fe3+ deposited and, when necessary, mobilized as Fe2+ metabolic requirements. In Pseudomonas aeruginosa, compartmentalized in bacterioferritin (BfrB), its mobilization requires specific binding a ferredoxin (Bfd) to reduce stored Fe3+. Blocking BfrB-Bfd complex leads irreversible accumulation BfrB cytosolic deprivation. Consequently,...
Ferritins are iron storage proteins assembled from 24 subunits into a spherical and hollow structure. The genomes of many bacteria harbor genes encoding two types ferritin-like proteins, the bacterial ferritins (Ftn) bacterioferritins (Bfr), which bind heme. genome P. aeruginosa PAO1 (like bacteria) contains coding for different molecules, ftnA (PA4235) bfrB (PA3531). reasons requiring presence distinct protein in cells have remained largely unexplained. Attempts to understand this issue...
Background/Objectives: The pulmonary administration of antibiotics can be advantageous in treating infections by promoting high intrapulmonary drug concentrations with reduced systemic exposure. However, limited benefits have been observed for versus other routes due to its rapid clearance from the lung. Here, effects structural modifications on epithelial permeability and antibacterial potency a third-generation cephalosporin were investigated improve understanding properties that promote...
The peptide pheromone cCF10 of Enterococcus faecalis is an intercellular signal for induction conjugative transfer plasmid pCF10 from donor cells to recipient cells. When a cell exposed recipient-produced cCF10, expression the pCF10-encoded aggregation substance (Asc10) and other conjugation gene products activated. Asc10 also increases enterococcal virulence in several models, when are grown animals or plasma, induced by means cCF10-sensing machinery. Plasmid carries two genes that function...
Burkholderia thailandensis produces a family of polyketide-peptide molecules called bactobolins, some which are potent antibiotics. We found that growth B. at 30°C versus 37°C resulted in increased production bactobolins. purified the three most abundant bactobolins and determined their activities against battery bacteria mouse fibroblasts. Two compounds showed strong both The third analog was much less assays. These results suggested target might be conserved across mammalian cells. To...