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Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenza biofilm formation

Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenza biofilm formation
Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenza biofilm formation
Nontypeable Haemophilus influenzae (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesized that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonization and biofilm evelopment. We used a primary epithelial cell co-culture model to investigate NTHi infection. Primary airway epithelial cells from PCD and non-PCD patients were differentiated to ciliation using air-liquid interface culture and then co-cultured with NTHi. NTHi adherence was greater on PCD epithelial cells compared to non-PCD cells (P<0.05) and the distribution of NTHi on PCD epithelium showed more aggregated NTHi in biofilms (P<0.001). Apart from defective ciliary motility, PCD cells did not significantly differ from non-PCD epithelial cells in the degree of ciliation and epithelial integrity or in cytokine, LL-37 and NO production. Treatment of PCD epithelia using exogenous NO and antibiotic significantly reduced NTHi viability in biofilms compared to antibiotic treatment alone. Impaired ciliary function was the primary defect in PCD airway epithelium underlying susceptibility to NTHi biofilm development compared with non-PCD epithelium. Although NO responses were similar, use of targeted NO with antibiotics enhanced killing of NTHi in biofilms, suggesting a novel therapeutic approach.
0903-1936
1-12
Walker, Woolf
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Jackson, Claire
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Allan, Raymond
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Collins, Samuel, Anthony
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Kelso, M.J.
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Rineh, Ardeshir
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Yepuri, Nageshwar R.
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Nicholas, Benjamin L.
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Lau, Laurie
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Johnston, David
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Lackie, Peter
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Faust, Saul
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Lucas, Jane
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Hall-Stoodley, Luanne
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Walker, Woolf
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Jackson, Claire
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Allan, Raymond
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
Collins, Samuel, Anthony
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Kelso, M.J.
a86ec82f-0b46-4875-a5ec-d87c6b6bf22f
Rineh, Ardeshir
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Yepuri, Nageshwar R.
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Nicholas, Benjamin L.
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Lau, Laurie
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Johnston, David
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Lackie, Peter
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Faust, Saul
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Lucas, Jane
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Hall-Stoodley, Luanne
94ebdc00-b549-4488-b15f-5310fb965f5b

Walker, Woolf, Jackson, Claire, Allan, Raymond, Collins, Samuel, Anthony, Kelso, M.J., Rineh, Ardeshir, Yepuri, Nageshwar R., Nicholas, Benjamin L., Lau, Laurie, Johnston, David, Lackie, Peter, Faust, Saul, Lucas, Jane and Hall-Stoodley, Luanne (2017) Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenza biofilm formation. European Respiratory Journal, 50 (3), 1-12. (doi:10.1183/13993003.00612-2017).

Record type: Article

Abstract

Nontypeable Haemophilus influenzae (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesized that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonization and biofilm evelopment. We used a primary epithelial cell co-culture model to investigate NTHi infection. Primary airway epithelial cells from PCD and non-PCD patients were differentiated to ciliation using air-liquid interface culture and then co-cultured with NTHi. NTHi adherence was greater on PCD epithelial cells compared to non-PCD cells (P<0.05) and the distribution of NTHi on PCD epithelium showed more aggregated NTHi in biofilms (P<0.001). Apart from defective ciliary motility, PCD cells did not significantly differ from non-PCD epithelial cells in the degree of ciliation and epithelial integrity or in cytokine, LL-37 and NO production. Treatment of PCD epithelia using exogenous NO and antibiotic significantly reduced NTHi viability in biofilms compared to antibiotic treatment alone. Impaired ciliary function was the primary defect in PCD airway epithelium underlying susceptibility to NTHi biofilm development compared with non-PCD epithelium. Although NO responses were similar, use of targeted NO with antibiotics enhanced killing of NTHi in biofilms, suggesting a novel therapeutic approach.

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ERJ Walker Jackson 2017 s1-ln26778661-508125724-1939656818Hwf-2019753590IdV54224988026778661PDF_HI0001 - Accepted Manuscript
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Accepted/In Press date: 4 June 2017
e-pub ahead of print date: 10 September 2017
Published date: September 2017
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 411831
URI: https://eprints.soton.ac.uk/id/eprint/411831
ISSN: 0903-1936
PURE UUID: ab2d5ebd-79d1-4085-a099-07726bb4b93c
ORCID for Samuel, Anthony Collins: ORCID iD orcid.org/0000-0003-1571-7410
ORCID for David Johnston: ORCID iD orcid.org/0000-0001-6703-6014
ORCID for Peter Lackie: ORCID iD orcid.org/0000-0001-7138-3764
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 27 Jun 2017 16:31
Last modified: 03 Dec 2019 06:01

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Contributors

Author: Woolf Walker
Author: Claire Jackson
Author: Raymond Allan
Author: Samuel, Anthony Collins ORCID iD
Author: M.J. Kelso
Author: Ardeshir Rineh
Author: Nageshwar R. Yepuri
Author: Benjamin L. Nicholas
Author: Laurie Lau
Author: David Johnston ORCID iD
Author: Peter Lackie ORCID iD
Author: Saul Faust ORCID iD
Author: Jane Lucas
Author: Luanne Hall-Stoodley

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