Arnold L Smith, MD

Professional History

Description of Research:

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.

Key Publications:

Daines DA, Bothwell M, Furrer J, Unrath W, Nelson K, Jarisch J, et al. (2005). Haemophilus influenzae luxS mutants form a biofilm and have increased virulence. Microb Pathog 39(3):87-96.

Erwin AL, Nelson KL, Mhlanga-Mutangadura T, Bonthuis PJ, Geelhood JL, Morlin G, et al. (2005). Characterization of genetic and phenotypic diversity of invasive nontypeable Haemophilus influenzae. Infect Immun 73(9):5853-5863.

42. Erwin AL, Allen S, Ho DK, Bonthuis PJ, Jarisch J, Nelson KL, et al. (2006). Role of lgtC in resistance of nontypeable Haemophilus influenzae strain R2866 to human serum. Infect Immun 74(11):6226-6235.

Erwin AL, Bonthuis PJ, Geelhood JL, Nelson KL, McCrea KW, Gilsdorf JR, et al. (2006). Heterogeneity in tandem octanucleotides within Haemophilus influenzae

lipopolysaccharide biosynthetic gene losA affects serum resistance. Infect Immun 74(6):3408-3414.

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

Fox KL, Dowideit SJ, Erwin AL, Srikhanta YN, Smith AL, Jennings MP (2007). Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression. Nucleic Acids Res 35(15):5242-5252.

Ho DK, Ram S, Nelson KL, Bonthuis PJ, Smith AL (2007). lgtC expression modulates resistance to C4b deposition on an invasive nontypeable Haemophilus influenzae. J Immunol 178(2):1002-1012.

Juhas M, Power PM, Harding RM, Ferguson DJ, Dimopoulou ID, Elamin AR, et al. (2007). Sequence and functional analyses of Haemophilus spp. genomic islands. Genome Biol 8(11):R237.

Smith AL, Erwin AL, Kline T, Unrath WC, Nelson K, Weber A, et al. (2007). Chloramphenicol is a substrate for a novel nitroreductase pathway in Haemophilus influenzae. Antimicrob Agents Chemother 51(8):2820-2829.

Erwin AL, Sandstedt SA, Bonthuis PJ, Geelhood JL, Nelson KL, Unrath WC, et al. (2008). Analysis of genetic relatedness of Haemophilus influenzae isolates by multilocus sequence typing. J Bacteriol 190(4):1473-1483. PMCID: PMC2238191.

Honors & Awards:

2003: Maureen Andrews Award for Mentoring, Society for Pediatric Research

2005: Paul di Sant'Agnes Distinguished Scientific Achievement Award, Cystic Fibrosis Foundation

2006: Arnold L. Smith, M.D. Endowment for Pediatric Junior Faculty, University of Washington - Children's Hospital and Regional Medical Center

2006: Ad hoc Reviewer, Lung Biology and Pathobiology Study Section, CSR, NIH

2007: Ad hoc member, Review Panel for Airway Diseases Division, NHLBI Program Project applications

2007: Ad hoc Reviewer, Medical Research Council, London, UK

2008: Ad hoc Reviewer, Wellcome Trust, London, UK

2008-Present: Interim Director, Center for Childhood Infections and Prematurity Research, Seattle Children's Research Institute