Short palate, lung, and nasal epithelial clone 1 has antimicrobial and antibiofilm activities against the Burkholderia cepacia complex

Saira Ahmad, Jean Tyrrell, William G. Walton, Ashutosh Tripathy, Matthew R. Redinbo, Robert Tarran

Research output: Research - peer-reviewArticle

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Abstract

The opportunistic bacteria of the Burkholderia cepacia complex (Bcc) are extremely pathogenic to cystic fibrosis (CF) patients, and acquisition of Bcc bacteria is associated with a significant increase in mortality. Treatment of Bcc infections is difficult because the bacteria are multidrug resistant and able to survive in biofilms. Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) is an innate defense protein that is secreted by the upper airways and pharynx. While SPLUNC1 is known to have antimicrobial functions, its effects on Bcc strains are unclear. We therefore tested the hypothesis that SPLUNC1 is able to impair Bcc growth and biofilm formation. We found that SPLUNC1 exerted bacteriostatic effects against several Bcc clinical isolates, including B. cenocepacia strain J2315 (50% inhibitory concentration [IC50] = 0.28 μM), and reduced biofilm formation and attachment (IC50 = 0.11 μM). We then determined which domains of SPLUNC1 are responsible for its antimicrobial activity. Deletions of SPLUNC1's N terminus and α6 helix did not affect its function. However, deletion of the α4 helix attenuated antimicrobial activity, while the corresponding α4 peptide displayed antimicrobial activity. Chronic neutrophilia is a hallmark of CF lung disease, and neutrophil elastase (NE) cleaves SPLUNC1. However, we found that the ability of SPLUNC1 to disrupt biofilm formation was significantly potentiated by NE pretreatment. While the impact of CF on SPLUNC1-Bcc interactions is not currently known, our data suggest that understanding this interaction may have important implications for CF lung disease.

LanguageEnglish (US)
Pages6003-6012
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2016

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Burkholderia cepacia complex
Palate
Nose
Clone Cells
Lung
Biofilms
Cystic Fibrosis
Bacteria
Leukocyte Elastase
Lung Diseases
Pharynx
Inhibitory Concentration 50
Peptides
Mortality
Growth
Infection
Proteins
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Short palate, lung, and nasal epithelial clone 1 has antimicrobial and antibiofilm activities against the Burkholderia cepacia complex. / Ahmad, Saira; Tyrrell, Jean; Walton, William G.; Tripathy, Ashutosh; Redinbo, Matthew R.; Tarran, Robert.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 10, 01.10.2016, p. 6003-6012.

Research output: Research - peer-reviewArticle

Ahmad, Saira ; Tyrrell, Jean ; Walton, William G. ; Tripathy, Ashutosh ; Redinbo, Matthew R. ; Tarran, Robert. / Short palate, lung, and nasal epithelial clone 1 has antimicrobial and antibiofilm activities against the Burkholderia cepacia complex. In: Antimicrobial Agents and Chemotherapy. 2016 ; Vol. 60, No. 10. pp. 6003-6012
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