Profile

Arnold L. Smith, MD

Arnold L. Smith, MD

Infectious Disease

On staff since October 1978

Research Center: Center for Global Infectious Disease Research

"I knew that infectious disease was the right choice for me when I cared for a newborn with an unusual case of bacterial meningitis. While caring for him, I recalled that this disease could be complicated by a brain abscess. I persuaded the radiologist to image his brain, even though there were no clinical indicators of an abscess. An abscess was identified and subsequently drained, and the infant recovered. His mother still sends me Christmas cards — 30 years later. Experiences like that motivate me to work to increase our understanding of childhood infections and to devise better ways of treating and ultimately preventing them."

Arnold L. Smith, MD: Professor of Pediatric Infectious Diseases. Haemophilus influenzae, a human-restricted bacterium that usually resides in the nasopharynx, is the focus of his lab.

Biology, genetics, antibiotic-resistant mechanisms, pathogenesis of disease and population structure are being investigated. Recent work has focused on the genes used by usually commensal, nontypeable strains to replicate in human blood and cause life-threatening disease. Population studies have indicated that there are subgroups of nontypeable H. influenzae that vary widely in virulence potential and are commensals or have the ability to cause mucosal infections such as otitis media and chronic bronchitis. Chromosomal-mediated antibiotic resistance, particularly to β-lactams, is increasing in prevalence, apparently due to “hot spots” in ftsI. Gene regulation of these events is under study.

Making A Difference

Overview

Research Description

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.

Research Focus Area

Infectious Disease

Awards and Honors

Award Name Award Description Awarded By Award Date
Inventor of the Year University of Washington 2009
Endowed Professorship for Training Pediatric Faculty in Research University of Washington and Seattle Children's Hospital 2006
Paul di Sant Agnese Distinguished Scientific Achievement Award Cystic Fibrosis Foundation 2005
Maureen Andrews Award for Mentoring Society for Pediatric Research 2003
Robert Gans Professorship Massachusetts General Hospital 2001
Service Award for Excellence in Teaching University of Missouri-Columbia 2000
Outstanding Teacher Award Children's Hospital and Regional Medical Center 1991
Citation of Merit (outstanding achievement and meritorious service in medicine) University of Missouri Alumni Association 1988
Charles A. Janeway Award (excellence in clinical teaching) 1978

Publications

  • Nakamura S, Shchepetov M, Dalia AB, Clark SE, Murphy TF, Sethi S, Gilsdorf JR, Smith AL, Weiser JN
    Molecular basis of increased serum resistance among pulmonary isolates of non-typeable Haemophilus influenzae.
    PLoS pathogens , 2011 Jan. : e1001247
  • Nelson KL, Smith AL
    Determination of capsulation status in Haemophilus influenzae by multiplex polymerase chain reaction.
    Diagnostic microbiology and infectious disease , 2010 Mar. : 235-40
  • Erwin AL, Sandstedt SA, Bonthuis PJ, Geelhood JL, Nelson KL, Unrath WC, Diggle MA, Theodore MJ, Pleatman CR, Mothershed EA, Sacchi CT, Mayer LW, Gilsdorf JR, Smith AL
    Analysis of genetic relatedness of Haemophilus influenzae isolates by multilocus sequence typing.
    Journal of bacteriology , 2008 Feb. : 1473-83
  • Smith AL, Erwin AL, Kline T, Unrath WC, Nelson K, Weber A, Howald WN
    Chloramphenicol is a substrate for a novel nitroreductase pathway in Haemophilus influenzae.
    Antimicrobial agents and chemotherapy , 2007 Aug. : 2820-9
  • Erwin AL, Smith AL
    Nontypeable Haemophilus influenzae: understanding virulence and commensal behavior.
    Trends in microbiology , 2007 Aug. : 355-62
  • Ho DK, Ram S, Nelson KL, Bonthuis PJ, Smith AL
    lgtC expression modulates resistance to C4b deposition on an invasive nontypeable Haemophilus influenzae.
    Journal of immunology (Baltimore, Md. : 1950) , 2007 Jan. 15 : 1002-12
  • Juhas M, Power PM, Harding RM, Ferguson DJ, Dimopoulou ID, Elamin AR, Mohd-Zain Z, Hood DW, Adegbola R, Erwin A, Smith A, Munson RS, Harrison A, Mansfield L, Bentley S, Crook DW
    Sequence and functional analyses of Haemophilus spp. genomic islands.
    Genome biology , 2007 : R237
  • Fox KL, Dowideit SJ, Erwin AL, Srikhanta YN, Smith AL, Jennings MP
    Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression.
    Nucleic acids research , 2007 : 5242-52
  • Erwin AL, Allen S, Ho DK, Bonthuis PJ, Jarisch J, Nelson KL, Tsao DL, Unrath WC, Watson ME Jr, Gibson BW, Apicella MA, Smith AL
    Role of lgtC in resistance of nontypeable Haemophilus influenzae strain R2866 to human serum.
    Infection and immunity , 2006 Nov. : 6226-35
  • Erwin AL, Bonthuis PJ, Geelhood JL, Nelson KL, McCrea KW, Gilsdorf JR, Smith AL
    Heterogeneity in tandem octanucleotides within Haemophilus influenzae lipopolysaccharide biosynthetic gene losA affects serum resistance.
    Infection and immunity , 2006 June : 3408-14
  • Daines DA, Bothwell M, Furrer J, Unrath W, Nelson K, Jarisch J, Melrose N, Greiner L, Apicella M, Smith AL
    Haemophilus influenzae luxS mutants form a biofilm and have increased virulence.
    Microbial pathogenesis , 2005 Sept. : 87-96
  • Erwin AL, Nelson KL, Mhlanga-Mutangadura T, Bonthuis PJ, Geelhood JL, Morlin G, Unrath WC, Campos J, Crook DW, Farley MM, Henderson FW, Jacobs RF, Mühlemann K, Satola SW, van Alphen L, Golomb M, Smith AL
    Characterization of genetic and phenotypic diversity of invasive nontypeable Haemophilus influenzae.
    Infection and immunity , 2005 Sept. : 5853-63
  • Green BA, Baranyi E, Reilly TJ, Smith AL, Zlotnick GW
    Certain site-directed, nonenzymatically active mutants of the Haemophilus influenzae P4 lipoprotein are able to elicit bactericidal antibodies.
    Infection and immunity , 2005 July : 4454-7
  • Bishop-Hurley SL, Schmidt FJ, Erwin AL, Smith AL
    Peptides selected for binding to a virulent strain of Haemophilus influenzae by phage display are bactericidal.
    Antimicrobial agents and chemotherapy , 2005 July : 2972-8
  • Watson ME Jr, Burns JL, Smith AL
    Hypermutable Haemophilus influenzae with mutations in mutS are found in cystic fibrosis sputum.
    Microbiology (Reading, England) , 2004 Sept. : 2947-58
  • Daines DA, Jarisch J, Smith AL
    Identification and characterization of a nontypeable Haemophilus influenzae putative toxin-antitoxin locus.
    BMC microbiology , 2004 July 26 : 30
  • Watson ME Jr, Jarisch J, Smith AL
    Inactivation of deoxyadenosine methyltransferase (dam) attenuates Haemophilus influenzae virulence.
    Molecular microbiology , 2004 July : 651-64
  • Daines DA, Smith AL
    Construction of a nontypeable Haemophilus influenzae-specific ectopic delivery vector.
    Journal of microbiological methods , 2004 June : 421-4
  • Raghunathan A, Price ND, Galperin MY, Makarova KS, Purvine S, Picone AF, Cherny T, Xie T, Reilly TJ, Munson R Jr, Tyler RE, Akerley BJ, Smith AL, Palsson BO, Kolker E
    In Silico Metabolic Model and Protein Expression of Haemophilus influenzae Strain Rd KW20 in Rich Medium.
    Omics : a journal of integrative biology , 2004 : 25-41
  • Bothwell MR, Smith AL, Phillips T
    Recalcitrant otorrhea due to Pseudomonas biofilm.
    Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery , 2003 Nov. : 599-601
  • Coleman HN, Daines DA, Jarisch J, Smith AL
    Chemically defined media for growth of Haemophilus influenzae strains.
    Journal of clinical microbiology , 2003 Sept. : 4408-10
  • 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, Makarova KS, Palsson BO, Smith AL
    Initial proteome analysis of model microorganism Haemophilus influenzae strain Rd KW20.
    Journal of bacteriology , 2003 Aug. : 4593-602
  • Ferkol T, Cohn LA, Phillips TE, Smith A, Davis PB
    Targeted delivery of antiprotease to the epithelial surface of human tracheal xenografts.
    American journal of respiratory and critical care medicine , 2003 May 15 : 1374-9
  • Smith AL, Fiel SB, Mayer-Hamblett N, Ramsey B, Burns JL
    Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of association in cystic fibrosis.
    Chest , 2003 May : 1495-502
  • Rodriguez CA, Avadhanula V, Buscher A, Smith AL, St Geme JW 3rd, Adderson EE
    Prevalence and distribution of adhesins in invasive non-type b encapsulated Haemophilus influenzae.
    Infection and immunity , 2003 Apr, : 1635-42
  • Daines DA, Cohn LA, Coleman HN, Kim KS, Smith AL
    Haemophilus influenzae Rd KW20 has virulence properties.
    Journal of medical microbiology , 2003 Apr, : 277-82
  • Graff GR, Weber A, Wessler-Starman D, Smith AL
    Montelukast pharmacokinetics in cystic fibrosis.
    The Journal of pediatrics , 2003 Jan. : 53-6
  • Williams BJ, Golomb M, Phillips T, Brownlee J, Olson MV, Smith AL
    Bacteriophage HP2 of Haemophilus influenzae.
    Journal of bacteriology , 2002 Dec. : 6893-905
  • Burd RS, Furrer JL, Sullivan J, Smith AL
    Murine beta-defensin-3 is an inducible peptide with limited tissue expression and broad-spectrum antimicrobial activity.
    Shock (Augusta, Ga.) , 2002 Nov. : 461-4
  • Swords WE, Chance DL, Cohn LA, Shao J, Apicella MA, Smith AL
    Acylation of the lipooligosaccharide of Haemophilus influenzae and colonization: an htrB mutation diminishes the colonization of human airway epithelial cells.
    Infection and immunity , 2002 Aug. : 4661-8
  • Kolker E, Purvine S, Picone A, Cherny T, Akerley BJ, Munson RS Jr, Palsson BO, Daines DA, Smith AL
    H. influenzae Consortium: integrative study of H. influenzae-human interactions.
    Omics : a journal of integrative biology , 2002 : 341-8