Covalent immobilization of antimicrobial agents on titanium prevents<i>Staphylococcus aureus</i>and<i>Candida albicans</i>colonization and biofilm formation

Kucharíková, Soňa; Gerits, Evelien; Brucker, Klaas De; Braem, Annabel; Čeh, Katerina; Majdič, Gregor; Španić, Tanja; Pogorevc, Estera; Verstraeten, Natalie; Tournu, Hélène; Delattin, Nicolas; Impellizzeri, Frédéric; Erdtmann, Martin; Krona, Annika; Lövenklev, Maria; Knežević, Miomir; Fröhlich, Mirjam; Zhang, Fei; Fauvart, Maarten; Silva, Wander José da; Vandamme, Katleen; Garcia-Forgas, Jordi; Cammue, Bruno P. A.; Michiels, Jan; Dijck, Patrick Van; Thevissen, Karin

doi:10.1093/jac/dkv437

Cited by 71 publications

(84 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While surfaces to which antibiotics are tethered have demonstrated promise for the potential inhibition of bacterial colonization, it is important to examine if such coated discs affect the growth of hBMSCs, which are an important cell type in bone tissue turnover and regeneration processes (8). One of the disadvantages of antibiotics covalently immobilized on Ti surfaces is that they inhibit hBMSC adhesion and proliferation, and multiple biomolecules must be coimmobilized on the Ti surfaces to achieve multiple biofunctions in order to avoid the disadvantage described above (41).…”

Section: Discussionmentioning

confidence: 99%

Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis

Nie

Long

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Infection is one of the most important causes of titanium implant failure in vivo. A developing prophylactic method involves the immobilization of antibiotics, especially vancomycin, onto the surface of the titanium implant. However, these methods have a limited effect in curbing multiple bacterial infections due to antibiotic specificity. In the current study, enoxacin was covalently bound to an aminefunctionalized Ti surface by use of a polyethylene glycol (PEG) spacer, and the bactericidal effectiveness was investigated in vitro and in vivo. The titanium surface was amine functionalized with 3-aminopropyltriethoxysilane (APTES), through which PEG spacer molecules were covalently immobilized onto the titanium, and then the enoxacin was covalently bound to the PEG, which was confirmed by X-ray photoelectron spectrometry (XPS). A spread plate assay, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to characterize the antimicrobial activity. For the in vivo study, Ti implants were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and implanted into the femoral medullary cavity of rats. The degree of infection was assessed by radiography, micro-computed tomography, and determination of the counts of adherent bacteria 3 weeks after surgery. Our data demonstrate that the enoxacin-modified PEGylated Ti surface effectively prevented bacterial colonization without compromising cell viability, adhesion, or proliferation in vitro. Furthermore, it prevented MRSA infection of the Ti implants in vivo. Taken together, our results demonstrate that the use of enoxacin-modified Ti is a potential approach to the alleviation of infections of Ti implants by multiple bacterial species.

show abstract

Section: Discussionmentioning

confidence: 99%

Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis

Nie

Long

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Even more, their common use in clinical settings makes them a suitable reservoir for nosocomial infections [35, 36]. Previous studies have demonstrated, to different extents, the efficiency of coating agents, such as chitosan [37], curcumin on dental resins [38], or the covalent immobilization of the antimicrobials vancomycin and caspofungin on titanium [39] preventing C. albicans adhesion and biofilm formation. Thus, we tested various biomaterials under steady-state laboratory conditions as well as physiological flow conditions where the abiotic surfaces were co-incubated or pre-treated with Filastatin.…”

Section: Introductionmentioning

confidence: 99%

A pre-therapeutic coating for medical devices that prevents the attachment of Candida albicans

Vargas-Blanco

Lynn

Rosch

et al. 2017

Ann Clin Microbiol Antimicrob

View full text Add to dashboard Cite

BackgroundHospital acquired fungal infections are defined as “never events”—medical errors that should never have happened. Systemic Candida albicans infections results in 30–50% mortality rates. Typically, adhesion to abiotic medical devices and implants initiates such infections. Efficient adhesion initiates formation of aggressive biofilms that are difficult to treat. Therefore, inhibitors of adhesion are important for drug development and likely to have a broad spectrum efficacy against many fungal pathogens. In this study we further the development of a small molecule, Filastatin, capable of preventing C. albicans adhesion. We explored the potential of Filastatin as a pre-therapeutic coating of a diverse range of biomaterials.MethodsFilastatin was applied on various biomaterials, specifically bioactive glass (cochlear implants, subcutaneous drug delivery devices and prosthetics); silicone (catheters and other implanted devices) and dental resin (dentures and dental implants). Adhesion to biomaterials was evaluated by direct visualization of wild type C. albicans or a non-adherent mutant edt1 −/− that were stained or fluorescently tagged. Strains grown overnight at 30 °C were harvested, allowed to attach to surfaces for 4 h and washed prior to visualization. The adhesion force of C. albicans cells attached to surfaces treated with Filastatin was measured using Atomic Force Microscopy. Effectiveness of Filastatin was also demonstrated under dynamic conditions using a flow cell bioreactor. The effect of Filastatin under microfluidic flow conditions was quantified using electrochemical impedance spectroscopy. Experiments were typically performed in triplicate.ResultsTreatment with Filastatin significantly inhibited the ability of C. albicans to adhere to bioactive glass (by 99.06%), silicone (by 77.27%), and dental resin (by 60.43%). Atomic force microcopy indicated that treatment with Filastatin decreased the adhesion force of C. albicans from 0.23 to 0.017 nN. Electrochemical Impedance Spectroscopy in a microfluidic device that mimic physiological flow conditions in vivo showed lower impedance for C. albicans when treated with Filastatin as compared to untreated control cells, suggesting decreased attachment. The anti-adhesive properties were maintained when Filastatin was included in the preparation of silicone materials.ConclusionWe demonstrate that Filastatin treated medical devices prevented adhesion of Candida, thereby reducing nosocomial infections.

show abstract

“…Another approach consists in immobilizing the drugs on medical surfaces. This has been described for caspofungin on propanal biosurfaces [187] and on titanium substrata which were therefore rendered less susceptible to C. albicans biofilm colonization, at the same time supporting osseointegration (integration of the implant into the bone) [188]. Osteocompatibility is an important trait to be taken into account, the lack of which can limit the clinical use of cytotoxic compounds (e.g., farnesol, [189]).…”

Section: Discussionmentioning

confidence: 99%

Fungal Metabolites for the Control of Biofilm Infections

Estrela

Abraham

2016

Agriculture

View full text Add to dashboard Cite

Many microbes attach to surfaces and produce a complex matrix of polymers surrounding their cells, forming a biofilm. In biofilms, microbes are much better protected against hostile environments, impairing the action of most antibiotics. A pressing demand exists for novel therapeutic strategies against biofilm infections, which are a grave health wise on mucosal surfaces and medical devices. From fungi, a large number of secondary metabolites with antimicrobial activity have been characterized. This review discusses natural compounds from fungi which are effective against fungal and bacterial biofilms. Some molecules are able to block the cell communication process essential for biofilm formation (known as quorum sensing), others can penetrate and kill cells within the structure. Several targets have been identified, ranging from the inhibition of quorum sensing receptors and virulence factors, to cell wall synthesizing enzymes. Only one group of these fungal metabolites has been optimized and made it to the market, but more preclinical studies are ongoing to expand the biofilm-fighting arsenal. The broad diversity of bioactive compounds from fungi, their activities against various pathogens, and the multi-target trait of some molecules are promising aspects of fungal secondary metabolites. Future screenings for biofilm-controlling compounds will contribute to several novel clinical applications.

show abstract

Covalent immobilization of antimicrobial agents on titanium preventsStaphylococcus aureusandCandida albicanscolonization and biofilm formation

Abstract: These data demonstrate the clinical potential of covalently bound VAN and CAS on Ti to reduce microbial biofilm formation without jeopardizing osseointegration.

Cited by 71 publications

References 46 publications

Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis

Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis

A pre-therapeutic coating for medical devices that prevents the attachment of Candida albicans

Fungal Metabolites for the Control of Biofilm Infections

Contact Info

Product

Resources

About