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dc.contributor.authorParducho, K.R.
dc.contributor.authorBeadell, B.
dc.contributor.authorLu, W.
dc.date.accessioned2020-06-01T18:26:13Z
dc.date.available2020-06-01T18:26:13Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085152837&doi=10.3389%2ffimmu.2020.00805&partnerID=40&md5=2b75917bd4e9e3cfcd5f8e53994b7a3c
dc.identifier.urihttp://hdl.handle.net/10713/12903
dc.description.abstractBiofilm production is a key virulence factor that facilitates bacterial colonization on host surfaces and is regulated by complex pathways, including quorum sensing, that also control pigment production, among others. To limit colonization, epithelial cells, as part of the first line of defense, utilize a variety of antimicrobial peptides (AMPs) including defensins. Pore formation is the best investigated mechanism for the bactericidal activity of AMPs. Considering the induction of human beta-defensin 2 (HBD2) secretion to the epithelial surface in response to bacteria and the importance of biofilm in microbial infection, we hypothesized that HBD2 has biofilm inhibitory activity. We assessed the viability and biofilm formation of a pyorubin-producing Pseudomonas aeruginosa strain in the presence and absence of HBD2 in comparison to the highly bactericidal HBD3. At nanomolar concentrations, HBD2 - independent of its chiral state - significantly reduced biofilm formation but not metabolic activity, unlike HBD3, which reduced biofilm and metabolic activity to the same degree. A similar discrepancy between biofilm inhibition and maintenance of metabolic activity was also observed in HBD2 treated Acinetobacter baumannii, another Gram-negative bacterium. There was no evidence for HBD2 interference with the regulation of biofilm production. The expression of biofilm-related genes and the extracellular accumulation of pyorubin pigment, another quorum sensing controlled product, did not differ significantly between HBD2 treated and control bacteria, and in silico modeling did not support direct binding of HBD2 to quorum sensing molecules. However, alterations in the outer membrane protein profile accompanied by surface topology changes, documented by atomic force microscopy, was observed after HBD2 treatment. This suggests that HBD2 induces structural changes that interfere with the transport of biofilm precursors into the extracellular space. Taken together, these data support a novel mechanism of biofilm inhibition by nanomolar concentrations of HBD2 that is independent of biofilm regulatory pathways. Copyright 2020 The Autors.en_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health (Grants NIH SC1 GM096916, NIH RISE GM061331, and NIH LA Basin Bridges to Ph.D. GM054939), the National Science Foundation (Grant NSF-MRI 1828334), the California State University Library Open Access Author Fund, and the College of Natural and Social Sciences at California State University Los Angeles (NSS Research and Scholarship Award 2018).en_US
dc.description.urihttps://doi.org/10.3389/fimmu.2020.00805en_US
dc.language.isoen_USen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Immunology
dc.subjectairwaysen_US
dc.subjectantimicrobial peptidesen_US
dc.subjectbiofilmen_US
dc.subjectcystic fibrosisen_US
dc.subjectepithelial cellsen_US
dc.subjectinnate immunityen_US
dc.subjectmucosaen_US
dc.subjectPseudomonas aeruginosaen_US
dc.titleThe Antimicrobial Peptide Human Beta-Defensin 2 Inhibits Biofilm Production of Pseudomonas aeruginosa Without Compromising Metabolic Activityen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fimmu.2020.00805


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