This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200509-1459OCv1 174/2/213    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Starner, T. D. Articles by McCray, P. B. Search for Related Content PubMed PubMed Citation Articles by Starner, T. D. Articles by McCray, P. B., Jr.

Haemophilus influenzae Forms Biofilms on Airway Epithelia

Implications in Cystic Fibrosis

Departments of Pediatrics and Microbiology, The University of Iowa, Iowa City, Iowa

Correspondence and requests for reprints should be addressed to Timothy D. Starner, M.D., The University of Iowa, Department of Pediatrics, 200 Hawkins Drive, Iowa City, IA 52242. E-mail: timothy-starner{at}uiowa.edu

Rationale: Nontypeable Haemophilus influenzae (NTHi) commonly infects patients with cystic fibrosis (CF), especially early in childhood. Bacteria biofilms are increasingly recognized as contributing to bacterial persistence and disease pathogenesis in CF.

Objectives: This study investigated ability of NTHi to form biofilms and its impact on airway epithelia using in vivo and in vitro analyses.

Methods: We evaluated bronchoalveolar lavage fluid from young patients with CF for evidence of NTHi biofilms. To further investigate the pathogenesis of NTHi in respiratory infections, we developed a novel in vitro coculture model of NTHi biofilm formation on polarized human airway epithelial cells grown at the air–liquid interface.

Measurements and Main Results: In bronchoalveolar lavage fluid samples from young, asymptomatic patients with CF, we found morphologic evidence suggestive of NTHi biofilm formation. In addition, 10 clinical NTHi isolates from patients with CF formed biofilms on plastic surfaces. NTHi formed biofilms on the apical surface of cultured airway epithelia. These biofilms exhibited decreased susceptibility to antibiotics and were adherent to epithelial surfaces. Airway epithelial cells remained viable throughout 4 d of coculture, and responded to NTHi with nuclear factor-B signaling, and increased chemokine and cytokine secretion.

Conclusions: NTHi formed adherent biofilms on the apical surface airway epithelia with decreased susceptibility to antibiotics, and respiratory cells exhibited inflammatory and host defense responses—evidence of a dynamic host–pathogen interaction. The data presented here have implications both for understanding early CF lung disease pathogenesis and for the treatment of early, asymptomatic colonization of patients with CF with H. influenzae.

Key Words: bacterial infections • inflammation • lung diseases

This article has been cited by other articles:

				S. Sekhar, R. Kumar, and A. Chakraborti Role of biofilm formation in the persistent colonization of Haemophilus influenzae in children from northern India J. Med. Microbiol., November 1, 2009; 58(11): 1428 - 1432. [Abstract] [Full Text] [PDF]

				S. Sethi and T. F. Murphy Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease N. Engl. J. Med., November 27, 2008; 359(22): 2355 - 2365. [Full Text] [PDF]

				M. J. Seidler, S. Salvenmoser, and F.-M. C. Muller Aspergillus fumigatus Forms Biofilms with Reduced Antifungal Drug Susceptibility on Bronchial Epithelial Cells Antimicrob. Agents Chemother., November 1, 2008; 52(11): 4130 - 4136. [Abstract] [Full Text] [PDF]

				G. G. Anderson, S. Moreau-Marquis, B. A. Stanton, and G. A. O'Toole In Vitro Analysis of Tobramycin-Treated Pseudomonas aeruginosa Biofilms on Cystic Fibrosis-Derived Airway Epithelial Cells Infect. Immun., April 1, 2008; 76(4): 1423 - 1433. [Abstract] [Full Text] [PDF]

				S. Fuschillo, A. De Felice, and G. Balzano Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms Eur. Respir. J., February 1, 2008; 31(2): 396 - 406. [Abstract] [Full Text] [PDF]

				T. D. Starner, J. D. Shrout, M. R. Parsek, P. C. Appelbaum, and G. Kim Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms Antimicrob. Agents Chemother., January 1, 2008; 52(1): 137 - 145. [Abstract] [Full Text] [PDF]

				M. J. A. van der Plas, G. N. Jukema, S.-W. Wai, H. C. M. Dogterom-Ballering, E. L. Lagendijk, C. van Gulpen, J. T. van Dissel, G. V. Bloemberg, and P. H. Nibbering Maggot excretions/secretions are differentially effective against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa J. Antimicrob. Chemother., January 1, 2008; 61(1): 117 - 122. [Abstract] [Full Text] [PDF]

				J. A. Jurcisek and L. O. Bakaletz Biofilms Formed by Nontypeable Haemophilus influenzae In Vivo Contain both Double-Stranded DNA and Type IV Pilin Protein J. Bacteriol., May 15, 2007; 189(10): 3868 - 3875. [Abstract] [Full Text] [PDF]

				F. J. Accurso Update in Cystic Fibrosis 2006 Am. J. Respir. Crit. Care Med., April 15, 2007; 175(8): 754 - 757. [Full Text] [PDF]

				W. Hong, K. Mason, J. Jurcisek, L. Novotny, L. O. Bakaletz, and W. E. Swords Phosphorylcholine Decreases Early Inflammation and Promotes the Establishment of Stable Biofilm Communities of Nontypeable Haemophilus influenzae Strain 86-028NP in a Chinchilla Model of Otitis Media Infect. Immun., February 1, 2007; 75(2): 958 - 965. [Abstract] [Full Text] [PDF]