PLUNC is a novel airway surfactant protein with anti-biofilm activity

Lokesh Gakhar; Jennifer A Bartlett; Jon Penterman; Dario Mizrachi; Pradeep K Singh; Rama K Mallampalli; S Ramaswamy; Paul B McCray Jr

doi:10.1371/journal.pone.0009098

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PLUNC is a novel airway surfactant protein with anti-biofilm activity

Journal article

Open access

Peer reviewed

PLUNC is a novel airway surfactant protein with anti-biofilm activity

Lokesh Gakhar, Jennifer A Bartlett, Jon Penterman, Dario Mizrachi, Pradeep K Singh, Rama K Mallampalli, S Ramaswamy and Paul B McCray Jr

PloS one, Vol.5(2), pp.e9098-e9098

02/09/2010

DOI: 10.1371/journal.pone.0009098

PMCID: PMC2817724

PMID: 20161732

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Abstract

The PLUNC ("Palate, lung, nasal epithelium clone") protein is an abundant secretory product of epithelia present throughout the conducting airways of humans and other mammals, which is evolutionarily related to the lipid transfer/lipopolysaccharide binding protein (LT/LBP) family. Two members of this family--the bactericidal/permeability increasing protein (BPI) and the lipopolysaccharide binding protein (LBP)--are innate immune molecules with recognized roles in sensing and responding to Gram negative bacteria, leading many to propose that PLUNC may play a host defense role in the human airways. Based on its marked hydrophobicity, we hypothesized that PLUNC may be an airway surfactant. We found that purified recombinant human PLUNC greatly enhanced the ability of aqueous solutions to spread on a hydrophobic surface. Furthermore, we discovered that PLUNC significantly reduced surface tension at the air-liquid interface in aqueous solutions, indicating novel and biologically relevant surfactant properties. Of note, surface tensions achieved by adding PLUNC to solutions are very similar to measurements of the surface tension in tracheobronchial secretions from humans and animal models. Because surfactants of microbial origin can disperse matrix-encased bacterial clusters known as biofilms [1], we hypothesized that PLUNC may also have anti-biofilm activity. We found that, at a physiologically relevant concentration, PLUNC inhibited biofilm formation by the airway pathogen Pseudomonas aeruginosa in an in vitro model. Our data suggest that the PLUNC protein contributes to the surfactant properties of airway secretions, and that this activity may interfere with biofilm formation by an airway pathogen.

Lung - microbiology

Epithelial Cells - metabolism

Humans

Biofilms - growth & development

Glycoproteins - metabolism

Molecular Sequence Data

Immunoblotting

Pulmonary Surfactants - metabolism

Pseudomonas aeruginosa - physiology

Lung - cytology

Phosphoproteins - metabolism

Lung - metabolism

Phosphoproteins - physiology

Epithelial Cells - cytology

Circular Dichroism

Biofilms - drug effects

Glycoproteins - genetics

Recombinant Proteins - metabolism

Amino Acid Sequence

Cells, Cultured

Recombinant Proteins - chemistry

Phosphoproteins - genetics

Pseudomonas aeruginosa - drug effects

Recombinant Proteins - pharmacology

Glycoproteins - physiology

Sequence Homology, Amino Acid

Hydrophobic and Hydrophilic Interactions

Details

Title: Subtitle: PLUNC is a novel airway surfactant protein with anti-biofilm activity
Creators: Lokesh Gakhar - Department of Biochemistry and Protein Crystallography Facility, University of Iowa, Iowa City, Iowa, United States of America
Jennifer A Bartlett
Jon Penterman
Dario Mizrachi
Pradeep K Singh
Rama K Mallampalli
S Ramaswamy
Paul B McCray Jr
Resource Type: Journal article
Publication Details: PloS one, Vol.5(2), pp.e9098-e9098
DOI: 10.1371/journal.pone.0009098
PMID: 20161732
PMCID: PMC2817724
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS GM087635 / NIGMS NIH HHS P01 HL-091842 / NHLBI NIH HHS P50 HL-61234 / NHLBI NIH HHS P50 HL061234 / NHLBI NIH HHS P30 ES05605 / NIEHS NIH HHS F32 GM087635 / NIGMS NIH HHS
Language: English
Date published: 02/09/2010
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
Record Identifier: 9984093347502771

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