• Faculty Member Photo

  • Arnold Smith MD
    Professor
    Email: click here
    Phone: (206) 987-2073

Arnold L. Smith received a MS and MD degree from the University of Missouri, and trained in Pediatrics on the Children’s Service at the Massachusetts General Hospital and at the Harriet Lane Home of Johns Hopkins Hospital. He served as a Research Associate at the National Institute of Health, and subsequently joining the faculty of Department of Pediatrics of Harvard Medical School serving in the Division of Infectious Disease at Boston Children’s Hospital. He served as a Professor of Pediatrics and adjunct Professor of Medicine and Microbiology at the University of Washington School of Medicine, and Chief of the Division of Infectious Disease from 1978 to 1994. From 1994 to 2002 he was Chair of the Department of Molecular Microbiology at the University of Missouri School of Medicine, returning to Seattle as the Director of the Microbial Pathogenesis Program at the Seattle Biomedical research Institute and Professor of Pathobiology until 2008. He is currently the interim Director for the Center for Childhood Infections and is a Professor of Pediatrics and adjunct Professor of Microbiology.

Undergraduate
University of Missouri, B.A., Biochemistry, 1958

Medical School
University of Missouri, M.D. and M.S., Biochemistry, 1964

The A.L. Smith lab seeks to understand the biology of the human-restricted bacterium Haemophilus influenzae, particularly those strains which lack genes for encapsulation – nontypeable H. influenzae (NTHi). NTHi are divisible into nine clades with members of one clade having the ability to cause invasive disease in normal children. The lab is in the process of defining the mechanism by which these emerging strains (which are not prevented by Hib-conjugate vaccines) evade host defense. Strategies used by NTHi to adapt to different anatomic foci include slipped-strand mispairing and DNA methylation. Mechanisms of colonization and invasion of human respiratory epithelium by NTHi are also under study.

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

Invited Review
Erwin, A.L. and A.L. Smith, 2007. Nontypeable Haemophilus influenzae: understanding virulence and commensal behavior. Trends Microbiol 15(8):355-362

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