Arnold Smith, MD
Professor of Pediatric Infectious Diseases
Email: click here
Phone: (206) 987-2073
The Smith lab seeks to understand the biology of Haemophilus influenzae, a ubiquitous bacterium, in humans and the mechanisms it uses in producing mucosal disease of the respiratory tract and sporadic invasive disease. The current focus is on regulation of gene expression, which differs from strain-to-strain and is both stochastic and directed; the role of intermediary metabolism in virulence is emphasized. A wide variety of model systems and techniques is used to gain insight into this bacterium. An additional pilot project is seeking to derive temperature stable protein vaccine to be used in the construction of protein-polysaccharide conjugates. The strategies used by Thermophiles is being used as a template for vaccine development.
University of Missouri, B.A., Biochemistry, 1958
University of Missouri, M.D. and M.S., Biochemistry, 1964
Smith, A.L., Fiel, S.B., Mayer-Hamblett, N., Ramsey, B., and Burns, J.L. 2003. Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of an association in cystic fibrosis. Chest 123(5):1495-1502
Kolker, E, Purvine, S Galperin, MY, Stolyar, S, Goodlett, DR, Nesvizhskii, AI, Keller, A, Xie, T, Eng, JK, Yi, E, Hood, L, Picone, AF, Cherny T, Tjaden, BC, Siegel, AF, Reilly, TJ, Markarova, KS, Pallsson, BO and Smith, AL. 2003. Initial Proteome analysis of model microorganism Haemophilus influenzae strain Rd KW20. J. Bacteriol 185:4593-4602
Coleman, HN, Daines, DA and Smith, AL 2003. Chemically defined media for growth of Haemophilus influenzae strains. J Clin Microbiol 41:4408-4410
Bothwell, MR, Smith, AL , and Phillips, T 2003. Recalcitrant otorrhea due to Pseudomonas biofilm. Otolarlyngol Head Neck Surg 129:599-601
Raghunathan, A, Price, ND, Galperin, MY, Makaraova, KS, Purvine, S Picone, AF, Cherny, T Xie, T, Reilly, TJ, Munson, R Jr., Tyler, RE, Akerley, BJ, Smith, AL, Palsson, BO and Kolker, E. 2004. In Silico metabolic model and Protein Expression of Haemophilus influenzae strain Rd KW20 in rich medium. OMICS 8:25-41
Daines, DA and Smith, AL. 2004. Construction of a nontypeable Haemophilus influenzae-specific ectopic delivery vector. J. Microb Methods 57:421-424
Watson, ME, Jarisch, J and Smith, AL. 2004. Inactivation of deoxyadenosine methyltransferase (dam) attenuates Haemophilus influenzae virulence. Molec Microbiol 53:651-664
Daines, DA, Jarisch, J and Smith, AL. 2004. Identification and characterization of a nontypeable Haemophilus influenzae putative toxin-antitoxin locus. BMC Microbiology 4:30-41
Watson, ME, Burns, JL and Smith, AL. 2004. Hypermutable Haemophilus influenzae with mutations in mutS are found in cystic fibrosis sputum. Microbiology 150 (Pt 9):2947-2958
Green, BA, Baranyi, E, Reilly, TG, Smith, AL, and GW Zlotnick. 2005. Certain Site-directed nonenzymatically active mutants of Haemophilus influenzae P4 Lipoprotein are able to elicit bactericidal antibodies. Infection & Immunity 73(7):4454-4457.
Bishop-Hurley, SL, Schmidt, FJ, Erwin, AE and AL Smith. 2005. Peptides selected for binding to an virulent strain of Haemophilus influenzae by phage display are bactericidal. Antimicrob Agents Chemotherap. 49(7):2972-2978.
Daines, DA, Bothwell, M, Furrer, J, Unrath, W, Nelson, K, Melrose, N. Grenier, L. Apicella, M and AL Smith. 2005. Haemophilus influenzae luxS mutants from a biofilm and have increased virulence. Microb Pathogenesis 39(3):87-96.
Erwin, AL, Nelson, K, Mhlanga-Mutangadura, T, Bonthuis, PJ, Geelhood, JL, Morlin, G, Unrath, WCT, Campos, J, Crook, DW, Farley, M, Henderson, FW, Jacobs, RF, Muhlemann, K, Satola, S, van Alphen, L, Golomb, M and AL Smith. 2005. Characterization of Genetic and Phenotypic Diversity of Invasive Nontypeable H. influenzae. Infect & Immun 73(9):5853-5863.
Erwin, AL, Bonthuis, P, Geelhood, JL, Nelson, KL, McCrea, KW, Gilsdorf, JR and AL Smith
2006. Heterogeneity in Tandem Octanucleotides within Haemophilus influenzae Lipopolysaccharide Biosynthhetic Gene losA affects Serum Resistance. Infect & Immun 74(6):3408-3414.
Erwin, AL, Allen, S, Ho, DK, Bonthuis, P, Jarisch, J, Nelson, KL, Tsao, DL, Unrath, WCT,
Watson, ME, Gibson, BW, Apicella, MA, and AL Smith. 2006. Role of lgtC in Resistance of Nontypeable Haemophilus influenzae Strain R2866 to Human Serum. Infect Immun 74(11):6226-6235.
Ho, DK, Ram, S, Nelson, KL, Bonthuis, PJ and AL Smith. 2007. lgtC Expression Modulates Resistance to C4b Deposition on an Invasive Nontypeable Haemophilus influenzae. J Immunol 178:1002- 1012.
Smith AL, Erwin AL, Kline T, Unrath WC, Nelson K, Weber A, Howald WN. 2007. Chloramphenicol is a substrate for a novel nitroreductase pathway in Haemophilus influenzae
Antimicrob Agents Chemother. 51(8):2820-2829
Fox, KL, Dowideit, SJ, Erwin, AL, Srikhanta, YN, Smith, AL and Jennings, MP. 2007. Haemophilus influenzae phase-varions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression. Nucleic Acids Res. 35(15):5242-5252.
Juhas, M, Power, PM, Harding, , PM, Ferguson, DJ, Dimopoulou, ID, Elamin, AR, Mohd-Zain, Z, Hood, DW, Adegbola, R, Erwin, AL, Smith, AL, Munson, RS, Harrison, A, Mansfield, L, Bentley, S, Crook, DW. 2007. Sequence and functional analyses of Haemophilus spp genomic islands. Genome Biol 8(11):R237
Erwin, AL, Sanstedt, SA, Bonthuis, PJ, Geelhood, JL, Nelson, KL, Unrath, WCT, Diggle, MA, Theodore, MJ, Pleatman, CR, Mothershed, EA,Sacchi, CT, Mayer, LW, Gilsdorf, JR and Smith, AL. 2008. Analysis of Genetic Relatedness of Haemophilus influenzae Isolates by Multilocus Sequence Typing. J Bacteriol 190(4):1473-1483
Erwin, A.L. and A.L. Smith, 2007. Nontypeable Haemophilus influenzae: understanding virulence and commensal behavior. Trends Microbiol 15(8):355-362