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. 2017 Apr 14;3(4):271-280.
doi: 10.1021/acsinfecdis.6b00173. Epub 2017 Feb 20.

Nonwoven Polymer Nanofiber Coatings That Inhibit Quorum Sensing in Staphylococcus aureus: Toward New Nonbactericidal Approaches to Infection Control

Michael J Kratochvil  1 , Tian Yang  1 , Helen E Blackwell  1 , David M Lynn  1   2
Affiliations

Nonwoven Polymer Nanofiber Coatings That Inhibit Quorum Sensing in Staphylococcus aureus: Toward New Nonbactericidal Approaches to Infection Control

Michael J Kratochvil et al. ACS Infect Dis. .

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.

Keywords: antivirulence; coatings; controlled release; electrospinning; nanofibers; polymers; quorum sensing.

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Figures

Figure 1
Figure 1
(A,B) Representative SEM images of electrospun PLGA nanofibers loaded with peptide 1 (A) or peptide 1FL (B). (C,D) Representative fluorescence microscopy images of electrospun PLGA nanofibers loaded with non-fluorescent peptide 1 (C) or fluorescently-labeled peptide 1FL (D).
Figure 2
Figure 2
Plot showing the release of peptide 1FL from PLGA nanofiber mats versus time upon incubation in PBS at 37 °C. Each point represents the mean values obtained from four different replicates with error bars representing standard error. Total release is normalized to the surface area of the fiber-coated substrates used in these experiments.
Figure 3
Figure 3
Plot showing the fluorescence of a GFP reporter strain of S. aureus, normalized to positive media controls, versus time for the incubation of substrates coated with nanofiber mats (see main text for additional details). Gray bars show the average normalized fluorescence for peptide 1-loaded PLGA nanofiber mats; white bars show average normalized fluorescence for control PLGA nanofiber mats (no peptide); black bars show average normalized fluorescence for positive media controls. All experiments were performed in three sets of four replicates; error bars represent standard error. All results obtained for peptide-loaded nanofiber mats were significant at the 95% confidence interval (p < 0.05) versus control PLGA mats and positive media controls.
Figure 4
Figure 4
Inhibition of hemolysis by group-I S. aureus promoted by QSI released from substrates coated with electrospun PLGA nanofiber mats. (A) Inhibition of hemolysis by S. aureus in liquid-culture assays over 14 days. Gray bars: peptide 1-loaded mats; white bars: control PLGA nanofiber mats (no peptide). Data are presented as averages of three biological replicates; error bars represent standard error. All results were significant at the 95% confidence interval (p < 0.05). (B–D) Representative images of hemolysis inhibition as observed on a solid blood agar plate inoculated with S. aureus. (B) Zone of hemolysis inhibition (dark red) observed around a non-woven substrate coated with a peptide 1-loaded mat; photographed from above under ambient lighting; the lighter red background indicates active hemolysis by S. aureus colonies in areas not adjacent to the substrate. (C) The same plate as in (B), but photographed when backlit to enhance contrast (see text); the yellow-orange background indicates active hemolysis by S. aureus colonies in areas not adjacent to the substrate. (D) No inhibition of hemolysis was observed in experiments using an otherwise identical uncoated mesh substrate; the plate was also photographed when backlit for clarity.
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