title: Nonwoven Polymer Nanofiber Coatings That Inhibit Quorum Sensing in Staphylococcus aureus: Toward New Nonbactericidal Approaches to Infection Control.
abstract: We report the fabrication and biological evaluation of nonwoven polymer nanofiber coatings that inhibit quorum sensing (QS) and virulence in the human pathogen Staphylococcus aureus. Our results demonstrate that macrocyclic peptide 1, a potent and synthetic nonbactericidal quorum sensing inhibitor (QSI) in S. aureus, can be loaded into degradable polymer nanofibers by electrospinning and that this approach can deposit QSI-loaded nanofiber coatings onto model nonwoven mesh substrates. The QSI was released over ∼3 weeks when these materials were incubated in physiological buffer, retained its biological activity, and strongly inhibited agr-based QS in a GFP reporter strain of S. aureus for at least 14 days without promoting cell death. These materials also inhibited production of hemolysins, a QS-controlled virulence phenotype, and reduced the lysis of erythrocytes when placed in contact with wild-type S. aureus growing on surfaces. This approach is modular and can be used with many different polymers, active agents, and processing parameters to fabricate nanofiber coatings on surfaces important in healthcare contexts. S. aureus is one of the most common causative agents of bacterial infections in humans, and strains of this pathogen have developed significant resistance to conventional antibiotics. The QSI-based strategies reported here thus provide springboards for the development of new anti-infective materials and novel treatment strategies that target virulence as opposed to growth in S. aureus. This approach also provides porous scaffolds for cell culture that could prove useful in future studies on the influence of QS modulation on the development and structure of bacterial communities.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kratochvil
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Blackwell
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.|Department of Chemical and Biological Engineering, University of Wisconsin-Madison , 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
authors.forename: David M
authors.identifier: 0000-0002-3140-8637
authors.initials: DM
authors.lastname: Lynn
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D057139:Nanofibers / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D006460:Hemolysin Proteins; D047028:Macrocyclic Compounds; D011108:Polymers
keywords: antivirulence; coatings; controlled release; electrospinning; nanofibers; polymers; quorum sensing