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PATHOGENICITY AND VIRULENCE |
1Seattle Biomedical Research Institute, Four Nickerson Street, Suite 200, Seattle, WA 98109, USA 2Department of Molecular Microbiology and Immunology, School of Medicine, University of MissouriColumbia, Columbia, MO 65212, USA 3Division of Infectious Disease, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Correspondence Arnold L. Smith arnold.smith{at}sbri.org
Received 11 July 2002 Accepted 20 November 2002
Haemophilus influenzae is a human-adapted commensal and pathogen that can cause mucosal infections such as sinusitis, otitis media and bronchitis. Certain strains also cause bacteraemia and meningitis. Clinical isolates are genetically heterogeneous and are often recalcitrant to standard genetic manipulation. H. influenzae strain Rd KW20 has traditionally been considered avirulent, since it does not survive in the bloodstream of animals, is readily killed by normal adult human sera and cannot colonize the nasopharynx of infant rats. The purpose of this study was to determine whether Rd KW20 could be used in certain infection models. It is shown here that strain Rd KW20 can invade certain human epithelial cell lines grown either as monolayers or as differentiated epithelium at the airliquid interface. In addition, Rd KW20 can invade a monolayer of immortalized human brain microvascular endothelial cells. Finally, this strain can replicate and survive in human bronchial xenografts for up to 3 weeks. The complete genomic sequence of Rd KW20 is available and it is readily amenable to genetic manipulation. These properties and the results reported here indicate that this strain is a viable alternative to the use of clinical isolates for the investigation of H. influenzae virulence.
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