S I Miller

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. pmc Genomic analysis of the emergence of 20th century epidemic dysentery
    Laurence Rohmer
    Department of Microbiology, University of Washington, Seattle, WA, USA
    BMC Genomics 15:355. 2014
  2. pmc Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway
    Lucas R Hoffman
    Department of Pediatrics, University of Washington, Seattle, Washington, USA
    PLoS Pathog 6:e1000712. 2010
  3. pmc Expression of the Salmonella spp. virulence factor SifA in yeast alters Rho1 activity on peroxisomes
    Dani B N Vinh
    Department of Medicine, Immunology, Microbiology, and Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Mol Biol Cell 21:3567-77. 2010
  4. pmc Yersinia pestis insecticidal-like toxin complex (Tc) family proteins: characterization of expression, subcellular localization, and potential role in infection of the flea vector
    Justin L Spinner
    Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA
    BMC Microbiol 12:296. 2012
  5. pmc Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains
    Laurence Rohmer
    Department of Genome Sciences, University of Washington, Campus Box 357710, 1705 NE Pacific Street Seattle, Washington 98195, USA
    Genome Biol 8:R102. 2007
  6. ncbi request reprint Salmonella: a model for bacterial pathogenesis
    M E Ohl
    Department of Medicine, Division of Infectious Diseases, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA
    Annu Rev Med 52:259-74. 2001
  7. ncbi request reprint LPS, TLR4 and infectious disease diversity
    Samuel I Miller
    Department of Medicine, University of Washington Medical School, Seattle, Washington 98195, USA
    Nat Rev Microbiol 3:36-46. 2005
  8. ncbi request reprint Did bacterial sensing of host environments evolve from sensing within microbial communities?
    Samuel I Miller
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Cell Host Microbe 1:85-7. 2007
  9. pmc PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance
    J S Gunn
    University of Washington, Seattle 98195, USA
    J Bacteriol 178:6857-64. 1996
  10. pmc A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides
    T Guina
    Departments of Microbiology, University of Washington, Seattle 98195, USA
    J Bacteriol 182:4077-86. 2000

Research Grants

  1. P. aeruginosa as a surrogate marker of cystic fibrosis
    Samuel Miller; Fiscal Year: 2006
  2. The Yersinia insecticidal toxin complex
    Samuel Miller; Fiscal Year: 2008

Detail Information

Publications94

  1. pmc Genomic analysis of the emergence of 20th century epidemic dysentery
    Laurence Rohmer
    Department of Microbiology, University of Washington, Seattle, WA, USA
    BMC Genomics 15:355. 2014
    ..Sd1 is only detected in the context of human infections, and the circumstances under which epidemics emerge and regress remain unknown...
  2. pmc Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway
    Lucas R Hoffman
    Department of Pediatrics, University of Washington, Seattle, Washington, USA
    PLoS Pathog 6:e1000712. 2010
    ....
  3. pmc Expression of the Salmonella spp. virulence factor SifA in yeast alters Rho1 activity on peroxisomes
    Dani B N Vinh
    Department of Medicine, Immunology, Microbiology, and Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Mol Biol Cell 21:3567-77. 2010
    ..Further definition of SifA activity on yeast peroxisomes could provide more insight into its role in regulating host membrane dynamics and small GTPases...
  4. pmc Yersinia pestis insecticidal-like toxin complex (Tc) family proteins: characterization of expression, subcellular localization, and potential role in infection of the flea vector
    Justin L Spinner
    Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA
    BMC Microbiol 12:296. 2012
    ..Previous microarray data indicate that the Tc genes are highly upregulated by Y. pestis while in the flea vector; however, their role in the infection of fleas and pathogenesis in the mammalian host is unclear...
  5. pmc Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains
    Laurence Rohmer
    Department of Genome Sciences, University of Washington, Campus Box 357710, 1705 NE Pacific Street Seattle, Washington 98195, USA
    Genome Biol 8:R102. 2007
    ....
  6. ncbi request reprint Salmonella: a model for bacterial pathogenesis
    M E Ohl
    Department of Medicine, Division of Infectious Diseases, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA
    Annu Rev Med 52:259-74. 2001
    ..This review explores the molecular basis of selected Salmonella virulence strategies, with an emphasis on general themes of bacterial pathogenesis as exemplified by Salmonella...
  7. ncbi request reprint LPS, TLR4 and infectious disease diversity
    Samuel I Miller
    Department of Medicine, University of Washington Medical School, Seattle, Washington 98195, USA
    Nat Rev Microbiol 3:36-46. 2005
    ..This review will examine the hypothesis that the variability of bacterial ligands such as LPS and their innate immune receptors is an important factor in determining the outcome of infectious disease...
  8. ncbi request reprint Did bacterial sensing of host environments evolve from sensing within microbial communities?
    Samuel I Miller
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Cell Host Microbe 1:85-7. 2007
    ..It is likely that mechanisms for sensing such markers evolved from systems that recognized cues present in microbial communities before the emergence of eukaryotes...
  9. pmc PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance
    J S Gunn
    University of Washington, Seattle 98195, USA
    J Bacteriol 178:6857-64. 1996
    ..These data suggest that resistance to the polymyxin-CAP family is controlled by a cascade of regulatory protein expression that activates transcription upon environmental sensing...
  10. pmc A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides
    T Guina
    Departments of Microbiology, University of Washington, Seattle 98195, USA
    J Bacteriol 182:4077-86. 2000
    ..PgtE is a posttranscriptionally regulated component of the PhoP/PhoQ regulon that contributes to Salmonella resistance to innate immunity...
  11. ncbi request reprint Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides
    L Guo
    Department of Microbiology, University of Washington, Seattle 98195, USA
    Cell 95:189-98. 1998
    ..Similarly, in response to Mg2+ limited growth, other enteric Gram-negative bacteria demonstrated increased lipid A acylation. Compounds that inhibit the ability to increase lipid A acylation may have utility as new antimicrobial agents...
  12. pmc Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways
    Tina Guina
    Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:2771-6. 2003
    ..Measurement of PQS in P. aeruginosa isolates from asymptomatic children with CF indicated that strains with increased synthesis of PQS are present during early colonization of CF patient airways...
  13. pmc Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients
    David A D'Argenio
    Department of Microbiology, University of Washington, Seattle, WA, USA
    Mol Microbiol 64:512-33. 2007
    ..Loss of LasR function may represent a marker of an early stage in chronic infection of the CF airway with clinical implications for antibiotic resistance and disease progression...
  14. pmc Inhibition of Salmonella enterica serovar Typhimurium lipopolysaccharide deacylation by aminoarabinose membrane modification
    Kiyoshi Kawasaki
    Department of Microbiology, University of Washington, Health Sciences Building, K140, Box 357710, 1959 Pacific St N E, Seattle, WA 98195, USA
    J Bacteriol 187:2448-57. 2005
    ..Taken together, these results suggest that PagL enzymatic deacylation is posttranslationally inhibited by membrane environments, which either sequester PagL from its substrate or alter its conformation...
  15. ncbi request reprint Deacylation and palmitoylation of lipid A by Salmonellae outer membrane enzymes modulate host signaling through Toll-like receptor 4
    Kiyoshi Kawasaki
    Department of Microbiology, University of Washington, Seattle, Washington 98195, USA
    J Endotoxin Res 10:439-44. 2004
    ..Compared with unmodified lipid A, the modified lipid A species are 10-100-fold less active. These results suggest that PagL and PagP modify lipid A to reduce TLR4-signaling as part of Salmonellae adaptation to the host environment...
  16. ncbi request reprint The Salmonella type III secretion translocon protein SspC is inserted into the epithelial cell plasma membrane upon infection
    C A Scherer
    Departments of Microbiology and Medicine, University of Washington, Box 357710, Seattle, WA 98195 7710, USA
    Mol Microbiol 37:1133-45. 2000
    ..These data indicate that insertion of SspC into the plasma membrane of target cells is required for invasion and effector molecule translocation and that the carboxyl terminus of SspC is essential for these functions...
  17. pmc A conserved amino acid sequence directing intracellular type III secretion by Salmonella typhimurium
    E A Miao
    Department of Microbiology, University of Washington, HSB K 140, Box 357710, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 97:7539-44. 2000
    ..Three STE genes (sspH1, sspH2, and sseI) are located within temperate bacteriophages, suggesting a common mechanism for the dissemination of more recently evolved STE...
  18. pmc Expression of microbial virulence proteins in Saccharomyces cerevisiae models mammalian infection
    C F Lesser
    Departments of Medicine and Microbiology, University of Washington, HSB K116, Box 357710, Seattle, WA 98195, USA
    EMBO J 20:1840-9. 2001
    ..Thus, study of bacterial virulence proteins in yeast is a powerful system to determine functions of these proteins, probe eukaryotic cellular processes and model mammalian infection...
  19. ncbi request reprint Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity
    R K Ernst
    University of Washington, Department of Medicine, HSB K-140, Box 357710, Seattle, WA 98195, USA
    Microbes Infect 3:1327-34. 2001
    ..This remodeling includes enzymes that modify lipopolysaccharide (LPS). Modified LPS promotes bacterial survival by increasing resistance to cationic antimicrobial peptides and by altered host recognition of LPS...
  20. ncbi request reprint Transcriptional activation of Salmonella typhimurium invasion genes by a member of the phosphorylated response-regulator superfamily
    C Johnston
    Department of Medicine, University of Washington, Seattle 98195, USA
    Mol Microbiol 22:715-27. 1996
    ..Furthermore, SirA phosphorylation is predicted to initiate a cascade of transcription-factor synthesis which results in invasion-gene transcription, Ssp secretion, and bacterial invasion of epithelia...
  21. ncbi request reprint 3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4
    Kiyoshi Kawasaki
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    J Biol Chem 279:20044-8. 2004
    ..These results suggest that the lipid A modifications reduce TLR4-signaling as part of Salmonellae adaptation to host environments...
  22. pmc An inhibitor of gram-negative bacterial virulence protein secretion
    Heather B Felise
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Cell Host Microbe 4:325-36. 2008
    ..This work provides a proof of concept that compounds with a broad spectrum of activity against Gram-negative bacterial secretion systems could be developed to prevent and treat bacterial diseases...
  23. ncbi request reprint Aminoglycoside antibiotics induce bacterial biofilm formation
    Lucas R Hoffman
    Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA
    Nature 436:1171-5. 2005
    ..Our results demonstrate that biofilm formation can be a specific, defensive reaction to the presence of antibiotics, and indicate that the molecular basis of this response includes alterations in the level of c-di-GMP...
  24. ncbi request reprint Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis
    Robert K Ernst
    Department of Microbiology, University of Washington, Health Sciences Building, K 140, Box 357710, Seattle, WA 98195, USA
    Environ Microbiol 5:1341-9. 2003
    ..Further characterization of P. aeruginosa diversity within the airways of individual CF patients may reveal common adaptations, perhaps mediated by gene loss, that suggest new opportunities for therapy...
  25. pmc PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A
    Samuel M Moskowitz
    Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Bacteriol 186:575-9. 2004
    ..Thus, P. aeruginosa possesses a mechanism that induces resistance to cationic antimicrobial peptides in response to environmental conditions...
  26. ncbi request reprint Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides
    Martin W Bader
    Departments of Microbiology and Laboratory Medicine, University of Washington Medical School, Seattle, WA 98195, USA
    Mol Microbiol 50:219-30. 2003
    ..Because bacterial resistance to oxidative stress and CAMP are induced during infection of animals, CAMP may be an important signal recognized by bacteria on colonization of animal tissues...
  27. pmc The PhoQ histidine kinases of Salmonella and Pseudomonas spp. are structurally and functionally different: evidence that pH and antimicrobial peptide sensing contribute to mammalian pathogenesis
    Lynne R Prost
    Department of Microbiology, University of Washington Medical School, Seattle, WA 98195, USA
    Mol Microbiol 69:503-19. 2008
    ....
  28. ncbi request reprint Salmonella typhimurium leucine-rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems
    E A Miao
    Department of Microbiology, University of Washington, Seattle 98195, USA
    Mol Microbiol 34:850-64. 1999
    ..S. typhimurium deleted for both sspH1 and sspH2 was not able to cause a lethal infection in calves, indicating that these genes participate in S. typhimurium virulence for animals...
  29. pmc A HilA-independent pathway to Salmonella typhimurium invasion gene transcription
    J L Rakeman
    Departments of Microbiology, University of Washington, Seattle, Washington 98195, USA
    J Bacteriol 181:3096-104. 1999
    ..These data define roles for SirC and SirA as part of a HilA-independent pathway to SPI1 gene expression. We postulate that HilA-independent activation of inv expression is important for efficient assembly and function of the SPI1 TTSS...
  30. ncbi request reprint PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance
    J S Gunn
    University of Washington, Department of Medicine, Seattle 98195, USA
    Mol Microbiol 27:1171-82. 1998
    ....
  31. pmc Large-insert genome analysis technology detects structural variation in Pseudomonas aeruginosa clinical strains from cystic fibrosis patients
    Hillary S Hayden
    Genome Center, University of Washington, Seattle, WA 98195, USA
    Genomics 91:530-7. 2008
    ..aeruginosa and validates a technology that complements emerging, short-read sequencing methods that are better suited to characterizing single-nucleotide polymorphisms than structural variation...
  32. pmc Precursor acquisition independent from ion count: how to dive deeper into the proteomics ocean
    Alexandre Panchaud
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, USA
    Anal Chem 81:6481-8. 2009
    ..5%) and achieved dynamic range (8 orders of magnitude at FDR < or = 0.5%), without any fractionation other than immuno-depletion of the seven most abundant proteins...
  33. doi request reprint Design and synthesis of bis-carbamate analogs of cyclic bis-(3'-5')-diguanylic acid (c-di-GMP) and the acyclic dimer PGPG
    Toni Kline
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nucleosides Nucleotides Nucleic Acids 27:1282-300. 2008
    ..A molecular docking simulation of the carbamate isostere suggests that this analog is capable of assuming the correct conformation and pose at a c-di-GMP binding site...
  34. pmc The Pseudomonas aeruginosa lipid A deacylase: selection for expression and loss within the cystic fibrosis airway
    Robert K Ernst
    Department of Medicine, University of Washington, HSB T 293, Box 357710, 1959 Pacific Street N E, Seattle, WA 98195, USA
    J Bacteriol 188:191-201. 2006
    ..Finally, deacylated lipid A species were not observed in some clinical P. aeruginosa isolates from patients with severe pulmonary disease, suggesting that loss of PagL function can occur during long-term adaptation to the CF airway...
  35. pmc Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression
    Lucas R Hoffman
    Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA
    J Cyst Fibros 8:66-70. 2009
    ..Pseudomonas aeruginosa with mutations in the transcriptional regulator LasR chronically infect the airways of people with cystic fibrosis (CF), yet the prevalence and clinical implications of lasR mutant infection are unknown...
  36. ncbi request reprint Metal bridges between the PhoQ sensor domain and the membrane regulate transmembrane signaling
    Uhn Soo Cho
    Department of Biological Structure, University of Washington, Seattle, WA 98195, USA
    J Mol Biol 356:1193-206. 2006
    ..Therefore, both PhoQ and the membrane are required for extracytosolic sensing and transmembrane signaling...
  37. pmc Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients
    Eric E Smith
    Genome Center, Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 103:8487-92. 2006
    ..aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease...
  38. pmc Substituted 2-imino-5-arylidenethiazolidin-4-one inhibitors of bacterial type III secretion
    Toni Kline
    Departments of Genome Sciences, Microbiology, and Medicine, University of Washington, Seattle, Washington 98195, USA
    J Med Chem 51:7065-74. 2008
    ....
  39. ncbi request reprint Prospects for the development and use of gram-negative bacterial virulence protein secretion inhibitors for prophylaxis and treatment of infectious diseases
    Heather B Felise
    Department of Microbiology, University of Washington, Seattle, Washington 98195, USA
    Crit Rev Immunol 30:69-77. 2010
    ....
  40. pmc Unique lipid a modifications in Pseudomonas aeruginosa isolated from the airways of patients with cystic fibrosis
    Robert K Ernst
    Department of Medicine, University of Washington, Seattle, WA 98195, USA
    J Infect Dis 196:1088-92. 2007
    ..None of the isolates from the environment or from patients with other conditions displayed these modifications. These results indicate that unique lipid A modifications occur in clinical P. aeruginosa CF isolates...
  41. ncbi request reprint Recognition of antimicrobial peptides by a bacterial sensor kinase
    Martin W Bader
    Department of Microbiology, University of Washington Medical School, 1959 NE Pacific Street, Seattle, Washington 98195, USA
    Cell 122:461-72. 2005
    ..Our findings reveal a molecular mechanism by which bacteria sense small innate immune molecules to initiate a transcriptional program that promotes bacterial virulence...
  42. pmc Use of phage display to identify potential Pseudomonas aeruginosa gene products relevant to early cystic fibrosis airway infections
    Christiane Beckmann
    Infectious Diseases Section, Children s Hospital and Regional Medical Center, 307 Westlake Ave N, Suite 300, Seattle, WA 98109, USA
    Infect Immun 73:444-52. 2005
    ..These results demonstrate the feasibility and validity of this novel approach and suggest potential targets for future development...
  43. ncbi request reprint Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin
    Shawn J Skerrett
    Department of Medicine, University of Washington School of Medicine, Seattle, 98104, USA
    Am J Physiol Lung Cell Mol Physiol 287:L143-52. 2004
    ..These data provide causal evidence that distal airway epithelial cells and the signals they transduce play a physiological role in lung inflammation in vivo...
  44. ncbi request reprint Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4
    Robert K Ernst
    Department of Medicine, HSB K 155, Box 357710, University of Washington, Seattle, WA 98195, USA
    J Endotoxin Res 9:395-400. 2003
    ..P. aeruginosa adaptation to the human airway may, therefore, play a fundamental role in the progressive lung damage associated with cystic fibrosis...
  45. ncbi request reprint Proteomic analysis of Pseudomonas aeruginosa grown under magnesium limitation
    Tina Guina
    Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, Washington 98195, USA
    J Am Soc Mass Spectrom 14:742-51. 2003
    ..aeruginosa outer membrane proteins. This study shows that large-scale quantitative proteomic technology can be successfully applied to the analysis of whole bacteria and to the discovery of functionally relevant biologic phenotypes...
  46. ncbi request reprint Human Toll-like receptor 4 recognizes host-specific LPS modifications
    Adeline M Hajjar
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Nat Immunol 3:354-9. 2002
    ..Thus, in contrast to mice, humans use TLR4 to recognize a molecular signature of bacterial-host adaptation to modulate the innate immune response...
  47. doi request reprint Determination and comparison of the Francisella tularensis subsp.novicida U112 proteome to other bacterial proteomes
    Laurence Rohmer
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    J Proteome Res 7:2016-24. 2008
    ..Comparison of this protein profile with other profiles previously published suggested that the genome size and number of genes involved in regulation have little effect on the number of proteins expressed in a given stable condition...
  48. pmc Synthesis of and evaluation of lipid A modification by 4-substituted 4-deoxy arabinose analogs as potential inhibitors of bacterial polymyxin resistance
    T Kline
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Bioorg Med Chem Lett 18:1507-10. 2008
    ..One compound diminished the transfer of l-Ara4N onto lipid A. These results suggest that small molecules might be designed that would effect the same reversal of bacterial resistance observed in genetic knockouts...
  49. ncbi request reprint Carrier-mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine
    M Perez-Melgosa
    Department of Immunology, University of Washington, Seattle, 98195, USA
    Eur J Immunol 31:2373-81. 2001
    ..Neither porins nor lipopolysaccharide fully reproduced the effects of OMPC. These studies indicate that OMPC acts both as carrier and adjuvant, and thereby enhances T cell-dependent antibody responses in human infants...
  50. pmc Transcription of the SsrAB regulon is repressed by alkaline pH and is independent of PhoPQ and magnesium concentration
    Edward A Miao
    Department of Microbiology, Health Sciences Building, University of Washington, Seattle, WA 98195, USA
    J Bacteriol 184:1493-7. 2002
    ..0 or at a lower pH, suggesting that alkaline pH represses SsrAB activation. In addition, the PhoPQ two-component system, which is also activated intracellularly, was not required for activation of SsrAB...
  51. pmc The Salmonella enterica serovar typhimurium translocated effectors SseJ and SifB are targeted to the Salmonella-containing vacuole
    Jeremy A Freeman
    Department of Microbiology, University of Washington, Seattle, Washington 98195, USA
    Infect Immun 71:418-27. 2003
    ..The contribution of SseJ to in vivo replication is identical in wild-type and sifA deletion backgrounds, suggesting that SseJ trafficking away from the SCV along Sifs is unnecessary for its virulence function...
  52. pmc A Salmonella enterica serovar typhimurium translocated leucine-rich repeat effector protein inhibits NF-kappa B-dependent gene expression
    Andrea Haraga
    Department of Microbiology, University of Washington, Seattle, Washington 98195 7710, USA
    Infect Immun 71:4052-8. 2003
    ..We propose that suppression of inflammatory responses by intracellular S. enterica serovar Typhimurium, and perhaps Shigella flexneri, contributes to bacterial colonization of host tissues and pathogenesis...
  53. pmc Asymmetrical distribution of the second messenger c-di-GMP upon bacterial cell division
    Matthias Christen
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Science 328:1295-7. 2010
    ..Thus, asymmetrical distribution of c-di-GMP was observed as part of cell division, which may indicate an important regulatory step in extracellular organelle biosynthesis or function...
  54. ncbi request reprint Activation of the bacterial sensor kinase PhoQ by acidic pH
    Lynne R Prost
    Department of Microbiology, University of Washington Medical School, Seattle, WA 98195, USA
    Mol Cell 26:165-74. 2007
    ..We propose a model of activation by antimicrobial peptides via disruption of the cation bridges and/or by acidification of the periplasm through destabilization of the interaction network...
  55. ncbi request reprint Type IV pili-mediated secretion modulates Francisella virulence
    Anthony J Hager
    Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, WA, USA
    Mol Microbiol 62:227-37. 2006
    ..novicida spread. Francisella human pathogenic strains contain a mutation in pepO predicted to abolish its secretion. Loss of PepO function may have contributed to evolution of highly virulent Francisellae...
  56. ncbi request reprint Purification and characterization of deacylated and/or palmitoylated lipid A species unique to Salmonella enterica serovar Typhimurium
    Kiyoshi Kawasaki
    Department of Microbiology, University of Washington, Seattle, Washington, USA
    J Endotoxin Res 11:57-61. 2005
    ..The modified lipid A species showed reduced ability to induce cellular signaling through Toll-like receptor 4, suggesting a specific function of the lipid A modifications in the pathogenesis of salmonellae infection...
  57. pmc SseJ deacylase activity by Salmonella enterica serovar Typhimurium promotes virulence in mice
    Maikke B Ohlson
    Department of Microbiology, University of Washington, Seattle, 98195, USA
    Infect Immun 73:6249-59. 2005
    ....
  58. ncbi request reprint A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1
    Andrea Haraga
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell Microbiol 8:837-46. 2006
    ..These data indicate that SspH1 may inhibit the host's inflammatory response by interacting with PKN1...
  59. doi request reprint The Salmonellae PhoQ sensor: mechanisms of detection of phagosome signals
    Lynne R Prost
    Department of Microbiology, Universtiy of Washington Medical School, Seattle, WA 98195, USA
    Cell Microbiol 10:576-82. 2008
    ....
  60. doi request reprint Genome-specific gas-phase fractionation strategy for improved shotgun proteomic profiling of proteotypic peptides
    Alexander Scherl
    Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA
    Anal Chem 80:1182-91. 2008
    ....
  61. ncbi request reprint Cyclic di-GMP as a bacterial second messenger
    David A D'Argenio
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Microbiology 150:2497-502. 2004
    ..Genetic evidence suggests that the GGDEF domain acts as a nucleotide cyclase for c-di-GMP synthesis while the EAL domain is a good candidate for the opposing activity, a phosphodiesterase for c-di-GMP degradation...
  62. pmc SpiC is required for translocation of Salmonella pathogenicity island 2 effectors and secretion of translocon proteins SseB and SseC
    Jeremy A Freeman
    Department of Microbiology, Medicine, University of Washington, Seattle, Washington 98195, USA
    J Bacteriol 184:4971-80. 2002
    ..SpiC was also required to secrete translocon proteins SseB and SseC but not translocated effector SseJ, indicating that lack of assembly of the translocon explains the spiC mutant phenotype...
  63. ncbi request reprint Bacterial vesicle formation as a mechanism of protein transfer to animals
    Samuel I Miller
    Department of Medicine, University of Washington, Seattle, WA 98195, USA
    Cell 115:2-3. 2003
    ..This discovery should stimulate work on the mechanism of protein sorting into vesicles and the role of vesicles in bacterial pathogenesis...
  64. pmc Burkholderia thailandensis as a model system for the study of the virulence-associated type III secretion system of Burkholderia pseudomallei
    Andrea Haraga
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Infect Immun 76:5402-11. 2008
    ..Therefore, we propose B. thailandensis as a useful BSL-1 model system to study the role of the Bsa TTSS during Burkholderia infection of mammalian cells and animals...
  65. pmc Lack of in vitro and in vivo recognition of Francisella tularensis subspecies lipopolysaccharide by Toll-like receptors
    Adeline M Hajjar
    Department of Medicine, University of Washington, Health Sciences Building, Box 357710, 1959 NE Pacific Street, Seattle, WA 98195, USA
    Infect Immun 74:6730-8. 2006
    ..These results suggest that poor innate recognition of F. tularensis allows the bacterium to evade early recognition by the host innate immune system to promote its pathogenesis for mammals...
  66. pmc Potential source of Francisella tularensis live vaccine strain attenuation determined by genome comparison
    Laurence Rohmer
    Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
    Infect Immun 74:6895-906. 2006
    ..Seven of these genes were demonstrated to be under stronger selective constraints, suggesting that they are the most probable to be the source of LVS attenuation and useful for a newly defined vaccine...
  67. ncbi request reprint Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington 98103, USA
    Nat Immunol 7:569-75. 2006
    ....
  68. ncbi request reprint Assembly of the type III secretion needle complex of Salmonella typhimurium
    Tyler G Kimbrough
    Department of Molecular and Cellular Biology, University of Washington, HSB K 140, Box 357710, Seattle, WA 98195, USA
    Microbes Infect 4:75-82. 2002
    ..Recent progress in the understanding of the assembly and architecture of the NC is reviewed...
  69. pmc Antimicrobial peptides activate the Rcs regulon through the outer membrane lipoprotein RcsF
    Carol Farris
    Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA
    J Bacteriol 192:4894-903. 2010
    ..These findings suggest that RcsFCDB activation in response to CAMP-induced membrane disorder is a result of a change in structure or availability of RcsF to the IM signaling constituents of the Rcs phosphorelay...
  70. ncbi request reprint Identification of PhoP-PhoQ activated genes within a duplicated region of the Salmonella typhimurium chromosome
    J S Gunn
    Department of Medicine, University of Washington, HSB K 140, Box 357710, Seattle, WA 98195, USA
    Microb Pathog 25:77-90. 1998
    ....
  71. ncbi request reprint Salmonella typhimurium secreted invasion determinants are homologous to Shigella Ipa proteins
    C J Hueck
    Department of Infectious Diseases and Microbiology, University of Washington, Seattle 98195, USA
    Mol Microbiol 18:479-90. 1995
    ..These data indicate that major secreted invasion determinants of S. typhimurium are structurally and functionally homolgous to S. flexneri Ipa proteins...
  72. pmc Characterization of protein cross-links via mass spectrometry and an open-modification search strategy
    Pragya Singh
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, USA
    Anal Chem 80:8799-806. 2008
    ..Utility of this method in identifying native cross-links was demonstrated by mapping disulfide bridges in RcsF, an outer membrane lipoprotein involved in Rcs phosphorelay...
  73. pmc Identification of an unconventional E3 binding surface on the UbcH5 ~ Ub conjugate recognized by a pathogenic bacterial E3 ligase
    Itay Levin
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 107:2848-53. 2010
    ..Rapid generation of UbcH5 ~ Ub(n) may allow for bacterially directed modification of eukaryotic target proteins with a completed poly-Ub chain, efficiently tagging host targets for destruction...
  74. pmc Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation
    Maikke B Ohlson
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell Host Microbe 4:434-46. 2008
    ..Similar to GEFs, SifA interacted with GDP-bound RhoA, and purified SseJ and RhoA formed a protein complex, suggesting that SifA, SKIP, SseJ, and RhoA family GTPases cooperatively promote host membrane tubulation...
  75. pmc A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease
    Dennis C Ko
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Am J Hum Genet 85:214-27. 2009
    ..These results demonstrate the utility of genome-wide cell-based association screens with microbes in the identification of naturally selected variants that can impact human health...
  76. pmc Analysis of the genome of the Escherichia coli O157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence
    Bridget R Kulasekara
    Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195, USA
    Infect Immun 77:3713-21. 2009
    ....
  77. pmc The Pseudomonas aeruginosa proteome during anaerobic growth
    Manhong Wu
    Department of Medicine, Microbiology, and Genome Sciences, University of Washington, Seattle, 98195, USA
    J Bacteriol 187:8185-90. 2005
    ..These results form the basis for future analyses of alterations in bacterial protein content during growth in various environments, including the cystic fibrosis airway...
  78. ncbi request reprint Salmonella effectors translocated across the vacuolar membrane interact with the actin cytoskeleton
    Edward A Miao
    Department of Microbiology, University of Washington, HSB K 140, Box 357710, Seattle, WA 98195 7710, USA
    Mol Microbiol 48:401-15. 2003
    ..However, a third intracellular virulence factor, spvB, which ADP-ribosylates actin, strongly inhibited VAP formation in HeLa cells, suggesting a more subtle effect for SspH2 and SseI on the actin cytoskeleton...
  79. pmc Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa
    Lucas R Hoffman
    Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 103:19890-5. 2006
    ....
  80. pmc Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system
    Toni Kline
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Bioorg Med Chem Lett 19:1340-3. 2009
    ..Many of these dimers inhibited the T3SS-dependent secretion of a virulence protein at concentrations lower than that of the original monomeric compound identified in our screen...
  81. ncbi request reprint Salmonella sensing of anti-microbial mechanisms to promote survival within macrophages
    Lynne R Prost
    Department of Microbiology, University of Washington, Seattle, WA 98195 7710, USA
    Immunol Rev 219:55-65. 2007
    ..In this review, we discuss mechanisms by which Salmonella interacts with macrophages and focus in detail on recent reports describing the role of antimicrobial peptides and pH in PhoQ activation...
  82. pmc Characterization of late acyltransferase genes of Yersinia pestis and their role in temperature-dependent lipid A variation
    Roberto Rebeil
    Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St, Hamilton, Montana 59840, USA
    J Bacteriol 188:1381-8. 2006
    ..This mutant was able to infect and block fleas as well as the parental wild-type strain, indicating that the low-temperature-dependent change to hexa-acylated lipid A synthesis is not required for survival in the flea gut...
  83. pmc Mouse paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria
    Hiroki Tanabe
    Department of Pathology, School of Medicine, College of Health Sciences, University of California, Irvine, CA 92697 4800, USA
    Infect Immun 73:2312-20. 2005
    ..Thus, mouse Paneth cells respond equivalently to purified bacterial cell envelope glycolipids, regardless of functional Tlr4, the structural properties of glycolipid acyl chains, or their association with virulence in humans...
  84. pmc pmrA(Con) confers pmrHFIJKL-dependent EGTA and polymyxin resistance on msbB Salmonella by decorating lipid A with phosphoethanolamine
    Sean R Murray
    Department of Biology, Yale University, New Haven, Connecticut, USA
    J Bacteriol 189:5161-9. 2007
    ....
  85. pmc mig-14 is a Salmonella gene that plays a role in bacterial resistance to antimicrobial peptides
    Igor E Brodsky
    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Bacteriol 184:3203-13. 2002
    ..Therefore, mig-14 contributes to Salmonella resistance to antimicrobial peptides by a mechanism that is not yet fully understood...
  86. ncbi request reprint Threonine phosphorylation times bacterial secretion
    Hemantha D Kulasekara
    Nat Cell Biol 9:734-6. 2007
  87. ncbi request reprint Variation in lipid A structure in the pathogenic yersiniae
    Roberto Rebeil
    Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St, Hamilton, MT 59840, USA
    Mol Microbiol 52:1363-73. 2004
    ....
  88. ncbi request reprint Comparison of a Salmonella typhimurium proteome defined by shotgun proteomics directly on an LTQ-FT and by proteome pre-fractionation on an LCQ-DUO
    Brook L Nunn
    Goodlett Laboratory
    Brief Funct Genomic Proteomic 5:154-68. 2006
    ....
  89. pmc PhoPQ-mediated regulation produces a more robust permeability barrier in the outer membrane of Salmonella enterica serovar typhimurium
    Takeshi Murata
    Department of Molecular and Cell Biology, 16 Barker Hall, University of California, Berkeley, CA 94720 3202, USA
    J Bacteriol 189:7213-22. 2007
    ..On the other hand, drug-induced killing assays suggest that the outer membrane containing unmodified lipid A may serve as a better barrier in the presence of high concentrations (e.g., 5 mM) of Mg(2+)...
  90. pmc Salmonella-induced filament formation is a dynamic phenotype induced by rapidly replicating Salmonella enterica serovar typhimurium in epithelial cells
    Cheryl L Birmingham
    Infection, Immunity, Injury and Repair IIIR Program, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8
    Infect Immun 73:1204-8. 2005
    ..The virulence factors SpvB and SseJ were found to negatively modulate Sif formation. Our findings demonstrate the complex and dynamic nature of the Sif phenotype...
  91. pmc Role of the Salmonella pathogenicity island 1 (SPI-1) protein InvB in type III secretion of SopE and SopE2, two Salmonella effector proteins encoded outside of SPI-1
    Kristin Ehrbar
    Institute of Microbiology, D BIOL, ETH Zurich, 8092 Zurich, Switzerland
    J Bacteriol 185:6950-67. 2003
    ..Our data demonstrate that effector proteins encoded within and outside of SPI-1 use the same chaperone for secretion via the SPI-1 TTSS...
  92. pmc Role for myosin II in regulating positioning of Salmonella-containing vacuoles and intracellular replication
    Julie A Wasylnka
    Cell Biology Program, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
    Infect Immun 76:2722-35. 2008
    ..These studies reveal a novel role for myosin II in controlling SCV dynamics during infection and suggest that SopB activates myosin II...
  93. ncbi request reprint Structural characterization of the molecular platform for type III secretion system assembly
    Calvin K Yip
    Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3
    Nature 435:702-7. 2005
    ..We propose that the YscJ/PrgK protein family functions as an essential molecular platform for TTSS assembly...
  94. pmc Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant cells in Pseudomonas aeruginosa biofilms
    Janus A J Haagensen
    Center for Biomedical Microbiology, BioCentrum DTU, Building 301, The Technical University of Denmark, DK 2800 Lyngby, Denmark
    J Bacteriol 189:28-37. 2007
    ..These results suggest that increased antibiotic tolerance in biofilms may be a consequence of differentiation into distinct subpopulations with different phenotypic properties...

Research Grants2

  1. P. aeruginosa as a surrogate marker of cystic fibrosis
    Samuel Miller; Fiscal Year: 2006
    ..Furthermore, the knowledge obtained from this proposal may direct the development of new therapeutic interventions for CF patients. ..
  2. The Yersinia insecticidal toxin complex
    Samuel Miller; Fiscal Year: 2008
    ..The goals of this proposal are to examine the role of a newly found toxin complex in Y. pestis flea colonization and/or transmission. [unreadable] [unreadable] [unreadable] [unreadable]..