Haemophilus influenzae Forms Biofilms on Airway Epithelia: Implications in Cystic Fibrosis

Timothy D Starner; Niu Zhang; GunHee Kim; Michael A Apicella; Paul B McCray

doi:10.1164/rccm.200509-1459OC

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Haemophilus influenzae Forms Biofilms on Airway Epithelia: Implications in Cystic Fibrosis

Journal article

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Peer reviewed

Haemophilus influenzae Forms Biofilms on Airway Epithelia: Implications in Cystic Fibrosis

Timothy D Starner, Niu Zhang, GunHee Kim, Michael A Apicella and Paul B McCray

American journal of respiratory and critical care medicine, Vol.174(2), pp.213-220

07/15/2006

DOI: 10.1164/rccm.200509-1459OC

PMCID: PMC2662906

PMID: 16675778

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Abstract

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-κB 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 .

lung diseases

bacterial infections

inflammation

D. Cystic Fibrosis

Details

Title: Subtitle: Haemophilus influenzae Forms Biofilms on Airway Epithelia: Implications in Cystic Fibrosis
Creators: Timothy D Starner - Departments of Pediatrics and Microbiology, The University of Iowa, Iowa City, Iowa
Niu Zhang - Departments of Pediatrics and Microbiology, The University of Iowa, Iowa City, Iowa
GunHee Kim - Departments of Pediatrics and Microbiology, The University of Iowa, Iowa City, Iowa
Michael A Apicella - Departments of Pediatrics and Microbiology, The University of Iowa, Iowa City, Iowa
Paul B McCray - Departments of Pediatrics and Microbiology, The University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: American journal of respiratory and critical care medicine, Vol.174(2), pp.213-220
DOI: 10.1164/rccm.200509-1459OC
PMID: 16675778
PMCID: PMC2662906
NLM abbreviation: Am J Respir Crit Care Med
ISSN: 1073-449X
eISSN: 1535-4970
Publisher: American Thoracic Society
Language: English
Date published: 07/15/2006
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093335402771

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