There is a dire need for infection prevention strategies that do not require the use of antibiotics, which exacerbate the rise of multi- and pan-drug resistant infectious organisms. An important ...target in this area is the bacterial attachment and subsequent biofilm formation on medical devices (e.g., catheters). Here we describe nonfouling, lubricant-infused slippery polymers as proof-of-concept medical materials that are based on oil-infused polydimethylsiloxane (iPDMS). Planar and tubular geometry silicone substrates can be infused with nontoxic silicone oil to create a stable, extremely slippery interface that exhibits exceptionally low bacterial adhesion and prevents biofilm formation. Analysis of a flow culture of Pseudomonas aeruginosa through untreated PDMS and iPDMS tubing shows at least an order of magnitude reduction of biofilm formation on iPDMS, and almost complete absence of biofilm on iPDMS after a gentle water rinse. The iPDMS materials can be applied as a coating on other polymers or prepared by simply immersing silicone tubing in silicone oil, and are compatible with traditional sterilization methods. As a demonstration, we show the preparation of silicone-coated polyurethane catheters and significant reduction of Escherichia coli and Staphylococcus epidermidis biofilm formation on the catheter surface. This work represents an important first step toward a simple and effective means of preventing bacterial adhesion on a wide range of materials used for medical devices.
Catheter‐associated urinary tract infections (CAUTIs) are one of the most commonly occurring hospital‐acquired infections. Current coating strategies to prevent catheter‐associated biofilm formation ...are limited by their poor long‐term efficiency and limited applicability to diverse materials. Here, the authors report a highly effective non‐fouling coating with long‐term biofilm prevention activity and is applicable to diverse catheters. The thin coating is lubricous, stable, highly uniform, and shows broad spectrum prevention of biofilm formation of nine different bacterial strains and prevents the migration of bacteria on catheter surface. The coating method is adapted to human‐sized catheters (both intraluminal and extraluminal) and demonstrates long‐term biofilm prevention activity over 30 days in challenging conditions. The coated catheters are tested in a mouse CAUTI model and demonstrate high efficiency in preventing bacterial colonization of both Gram‐positive and Gram‐negative bacteria. Furthermore, the coated human‐sized Foley catheters are evaluated in a porcine CAUTI model and show consistent efficiency in reducing biofilm formation by Escherichia coli (E. coli) over 95%. The simplicity of the coating method, the ability to apply this coating on diverse materials, and the high efficiency in preventing bacterial adhesion increase the potential of this method for the development of next generation infection resistant medical devices.
A highly effective non‐fouling coating with long‐term biofilm prevention activity is developed and applied to diverse catheters. The thin coating is lubricous, stable, highly uniform, and shows broad‐spectrum prevention of biofilm formation. The coated human‐sized Foley catheters are evaluated in a porcine CAUTI model and show consistent efficiency in reducing biofilm formation by E. coli over 95%.
Biofilm formation in Staphylococcus aureus causes an increase in antibiotics resistance in chronic diseases, including osteomyelitis, endocarditis, and wound infection. The S. aureus biofilm ...structure is composed of polysaccharide, protein, and external DNA. Bacterial cells in the biofilm compose of resistant persister cells and exhibit multidrug resistance. The emergence of multidrug resistant S. aureus strains is a health problem now. In the S. aureus biofilm state, susceptibility to antibiotics even vancomycin is reduced and eradication of bacteria is challenging. In the present review, we studied the structure of biofilm, antibiotic resistant in biofilm state, and biofilm prevention strategies in S. aureus. Infections due to S. aureus are expensive and susceptibility to antibiotics is reduced in biofilm state and several methods, including anti-biofilm agents and vaccine should be applied to treat diseases related to biofilm. For prevention and inhibition of biofilm, application of antiadhesion agents and vaccines based on biofilm genes is recommended. Multivalent vaccines based on biofilm genes, including clumping factor A, poly-β (1-6)-N-acetylglucosamine, collagen adhesin, and fibronectin binding protein in S. aureus can be beneficial for preventing initial attachment and biofilm formation.
•A detailed review on biofilm formation genes and antibiotic resistance mechanisms in the biofilm state in S. aureus.•An exclusive review of vaccines based on biofilm and adhesion genes against S. aureus.•We reviewed new biofilm prevention methods based on bacteriophage and nanoparticles in S. aureus.
Implant-associated infections (IAIs) can cause serious problems due to the difficult-to-treat nature of the biofilms formed on the implant surface. In mature biofilms, the matrix, which consists of ...polysaccharides, proteins, lipids and extracellular DNA (eDNA), forms a protective environment for the residing bacteria, shielding them from antibiotics and host defenses. Recently, the indirect prevention of biofilm growth through the degradation of eDNA using an enzyme, such as deoxyribonuclease (DNase) I, has gained attention and is regarded as a promising strategy in the battle against IAIs. In this study, coatings of DNase I were applied on titanium implant materials and their anti-infective properties were investigated. First, the effectiveness of alternating current electrophoretic deposition (AC-EPD) as a novel processing route to apply DNase I on titanium was examined and compared with the commonly applied diffusion methodology (i.e. classic dipping). For the same processing time, the use of AC-EPD in combination with a polydopamine (PDA) coupling chemistry on the titanium electrode surface significantly increased the protein deposition yield as compared to classic dipping, thereby yielding homogeneous coatings with a thickness of 12.8 nm and an average surface roughness, Sa, of ∼20 nm. X-ray photoelectron spectroscopy confirmed the presence of peptide bonds on all DNase-coated substrates. Time-of-flight secondary ion mass spectrometry detected a more dense DNase I layer in the case of AC-EPD for electrodes coupled as anode during the high-amplitude half cycle of the AC signal. The enzyme activity, release kinetics, and shelf life of DNase I coatings were monitored in real-time using a quantitative qDNase assay. The activity of DNase I coatings produced using AC-EPD was three time higher than for coatings prepared by classic dipping. For both deposition methods, a high initial burst release was observed within the first 2 h, while some activity was still retained at the surface after 7 days. This can be explained by the stable attachment of a small fraction of DNase to the surface through covalent bonding to the PDA layer, while superimposing DNase deposits were only loosely bound and therefore released rapidly upon immersion in the medium. Interestingly, coatings prepared with AC-EPD exhibited a prolonged, gradual release of DNase activity. The AC-EPD DNase coatings significantly reduced biofilm formation of both Staphylococcus epidermidis and Pseudomonas aeruginosa up to 20 h, whereas DNase coatings prepared by short classic dipping only reduce S. epidermidis biofilm formation, and this to a lesser extent as compared to AC-EPD DNase coatings. Overall, this study indicates that AC-EPD allows to rapidly concentrate DNase I on PDA-functionalized titanium, while maintaining the enzyme activity and anti-infective ability. This highlights the potential of AC-EPD as a time-efficient coating strategy (as opposed to the much slower dip-coating methodologies) for bioactive molecules in a wide variety of biomedical applications.
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•Introduction of AC-EPD as alternative to classic dipping as fast method to deposit DNase I coatings.•AC-EPD enabled the deposition of dense, homogenous DNase I coating.•AC-EPD maintained enzyme activity, increasing activity threefold compared to dip coatings.•The majority of the coated activity was quickly released, while a small fraction was stably retained.•AC-EPD coatings more effectively reduced S. epidermidis and P. aeruginosa biofilms.
Bacteria-mediated diseases are a global healthcare concern due to the development and spread of antibiotic-resistant strains. Cationic compounds are considered membrane active biocidal agents having ...a great potential to control bacterial infections, while limiting the emergence of drug resistance. Herein, the versatile and simple layer-by-layer (LbL) technique is used to coat alternating multilayers of an antibacterial aminocellulose conjugate and the biocompatible hyaluronic acid on biocompatible polymer nanoparticles (NPs), taking advantage of the nanosize of these otherwise biologically inert templates. Stable polyelectrolyte-decorated particles with an average size of 50 nm and ζ potential of +40.6 mV were developed after five LbL assembly cycles. The antibacterial activity of these NPs against the Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli increased significantly when the polycationic aminocellulose was in the outermost layer. The large number of amino groups available on the particle surface, together with the nanosize of the multilayer conjugates, improved their interaction with bacterial membrane phospholipids, leading to membrane disruption, as confirmed by a Langmuir monolayer model, and the 10 logs reduction for both bacteria. The biopolymer decorated NPs were also able to inhibit the biofilm formation of S. aureus and E. coli by 94 and 40%, respectively, without affecting human cell viability. The use of LbL-coated NPs appears to be a promising antibiotic-free alternative for controlling bacterial infections using a low amount of antimicrobial agent.
Bacteria often colonize in-dwelling medical devices and grow as complex biofilm communities of cells embedded in a self-produced extracellular polymeric matrix, which increases their resistance to ...antibiotics and the host immune system. During biofilm growth, bacterial cells cooperate through specific quorum-sensing (QS) signals. Taking advantage of this mechanism of biofilm formation, we hypothesized that interrupting the communication among bacteria and simultaneously degrading the extracellular matrix would inhibit biofilm growth. To this end, coatings composed of the enzymes acylase and α-amylase, able to degrade bacterial QS molecules and polysaccharides, respectively, were built on silicone urinary catheters using a layer-by-layer deposition technique. Multilayer coatings of either acylase or amylase alone suppressed the biofilm formation of corresponding Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus. Further assembly of both enzymes in hybrid nanocoatings resulted in stronger biofilm inhibition as a function of acylase or amylase position in the layers. Hybrid coatings, with the QS-signal-degrading acylase as outermost layer, demonstrated 30% higher antibiofilm efficiency against medically relevant Gram-negative bacteria compared to that of the other assemblies. These nanocoatings significantly reduced the occurrence of single-species (P. aeruginosa) and mixed-species (P. aeruginosa and Escherichia coli) biofilms on silicone catheters under both static and dynamic conditions. Moreover, in an in vivo animal model, the quorum quenching and matrix degrading enzyme assemblies delayed the biofilm growth up to 7 days.
Respiratory infections from opportunistic bacterial pathogens (OBPs) have heightened research interests in drinking water distribution systems, premise plumbing, and point-of-use technologies. In ...particular, biofilm growth in showerheads increases OBP content, and inhalation of shower aerosols is a major exposure route for Legionellae and Mycobacteria infections. Incorporation of UVC LEDs into showerheads has thus been proposed as a point-of-use option for healthcare facilities. Herein we have examined incongruities between the nature of OBP contamination in shower water and the hypothetical application of conventional UV disinfection engineering concepts. Effective UV dosing within showerheads must overcome significant shielding effects imparted by the biological matrices in which common OBPs reside, including biofilm particles and protozoan hosts. Furthermore, prevention of biofilm growth in showerhead interiors requires a different UV irradiation approach and is lacking in established design parameters. Development of showerhead devices is also likely to face a trade-off between bathing functionality and simpler form factors that are more conducive to internal UV irradiation.
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•Future use of UV LEDs in showerheads may prevent opportunistic pathogen inhalation.•Bacteria in biofilm flocs and protozoa require higher doses than planktonic forms.•Suspended bacteria may be targeted in the bulk stream with a high intensity approach.•Continuous low intensity irradiation can prevent biofilms but has not been studied.•Device design must consider bathing utility and use aspects of healthcare settings.
Natural compounds and their derivatives have become the source of new generation antimicrobials to address the growing concern of antimicrobial resistance. The polyphenols present in the edible crops ...are traditionally used for preventing infections. Conjugation with cationic triphenylphosphonium (TPP) is used for synthesizing antimicrobials and to evade resistance development. Here, we report the antifungal and antibiofilm efficacy of TPP-conjugated curcumin (TPP-curcumin) on standard and clinical strains of C. albicans for the first time in comparison with native curcumin and common antifungal drugs. TPP-curcumin showed strong antifungal activity on Candida strains with MIC and MFC values of 3.75 and 5 μM, respectively. The antifungal and antibiofilm activity of TPP-curcumin was several fold effective than native curcumin and fluconazole. In vitro time-kill kinetics revealed complete killing of 106 cells mL−1 within 9 h exposure to TPP-curcumin. TPP-curcumin exhibited biofilm prevention, killing of biofilm-cells and biofilm dispersal activities. The biological activity measurements demonstrated that TPP-curcumin induces cell membrane damage, reactive oxygen species generation, mitochondrial dysfunction and inhibition of NAD(P)H-dependent dehydrogenases in C. albicans cells. The yeast to hyphal growth transition pivotal to pathogenesis and biofilm formation was strongly inhibited by TPP-curcumin. Together, these data demonstrated that TPP-curcumin elicits strong antifungal and antibiofilm activities by impacting multiple cellular targets. The TPP-conjugation enhanced the solubility and biofilm prevention activities in drug-resistant C. albicans strains. The strong antibiofilm activity together with impact on multiple cellular targets is promising for considering TPP-curcumin for developing or augmenting antifungal therapies for preventing drug-resistant Candida infections.
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•First report on antifungal and antibiofilm action of TPP-curcumin or Mitocurcumin.•Rapid and complete killing of Candida albicans cells was achieved within 9 h using TPP-curcumin.•Effective biofilm prevention and eradication of pre-formed Candida biofilms by TPP-curcumin.•MitoCur induced membrane damage, oxidative stress and mitochondrial dysfunction in Candida cells.•Yeast to filamentous hyphae transition was inhibited by sub-inhibitory concentrations of TPP-curcumin.
The present study explored the effect of quercetin on the expression of virulence genes actA, inlA, inlC, and their regulatory components, sigB and prfA, in L. monocytogenes. Furthermore, the ...physicochemical changes on the surface, membrane permeability, and biofilm formation of quercetin-treated bacteria were evaluated. An inhibitory dose-dependent effect of quercetin (0.1–0.8 mM) was observed on the cell attachment on stainless steel at 2 and 6 h at 37 °C. Quercetin at 0.8 mM prevented the biofilm formation on stainless steel surfaces after 6 h of incubation at 37 °C, while the untreated bacteria formed biofilms with a cell density of 5.1 Log CFU/cm2. The microscopic analysis evidenced that quercetin at 0.2 mM decreased the biovolume and covered area of the attached micro-colonies. Also, sigB, prfA, inlA, inlC, and actA genes were downregulated by 7–29 times lower compared to untreated bacteria. In addition, quercetin decreased the superficial cell charge, increased the membrane permeability, and its surface hydrophobicity. These results demonstrated that quercetin prevented biofilm formation, repressed the genes of stress and virulence of L. monocytogenes and also altered the physicochemical cell properties.
•Quercetin increased the membrane permeability and affected the physicochemical properties.•Virulence genes and their regulatory components were downregulated by quercetin.•Quercetin inhibited the biofilm development of L. monocytogenes.
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