scholarly journals Efficacy of Ethanol against Candida albicans and Staphylococcus aureus Polymicrobial Biofilms

2012 ◽  
Vol 57 (1) ◽  
pp. 74-82 ◽  
Author(s):  
Brian M. Peters ◽  
Raven M. Ward ◽  
Hallie S. Rane ◽  
Samuel A. Lee ◽  
Mairi C. Noverr
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Bacterial Pathogen ◽  
Content Type ◽  
Environmental Surfaces ◽  
Lock Solution ◽  
Lock Therapy ◽  
Catheter Lock ◽  
Therapy Model

ABSTRACTCandida albicans, an opportunistic fungus, andStaphylococcus aureus, a bacterial pathogen, are two clinically relevant biofilm-forming microbes responsible for a majority of catheter-related infections, with such infections often resulting in catheter loss and removal. Not only do these pathogens cause a substantial number of nosocomial infections independently, but also they are frequently found coexisting as polymicrobial biofilms on host and environmental surfaces. Antimicrobial lock therapy is a current strategy to sterilize infected catheters. However, the robustness of this technique against polymicrobial biofilms has remained largely untested. Due to its antimicrobial activity, safety, stability, and affordability, we tested the hypothesis that ethanol (EtOH) could serve as a potentially efficacious catheter lock solution againstC. albicansandS. aureusbiofilms. Therefore, we optimized the dose and time necessary to achieve killing of both monomicrobial and polymicrobial biofilms formed on polystyrene and silicone surfaces in a static microplate lock therapy model. Treatment with 30% EtOH for a minimum of 4 h was inhibitory for monomicrobial and polymicrobial biofilms, as evidenced by XTT {sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide inner salt} metabolic activity assays and confocal microscopy. Experiments to determine the regrowth of microorganisms on silicone after EtOH treatment were also performed. Importantly, incubation with 30% EtOH for 4 h was sufficient to kill and inhibit the growth ofC. albicans, while 50% EtOH was needed to completely inhibit the regrowth ofS. aureus. In summary, we have systematically defined the dose and duration of EtOH treatment that are effective against and prevent regrowth ofC. albicansandS. aureusmonomicrobial and polymicrobial biofilms in anin vitrolock therapy model.

scholarly journals Candida albicans Impacts Staphylococcus aureus Alpha-Toxin Production via Extracellular Alkalinization

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Olivia A. Todd ◽  
Mairi C. Noverr ◽  
Brian M. Peters
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Quorum Sensing ◽  
Bacterial Pathogen ◽  
Toxin Production ◽  
Extracellular Ph ◽  
Morbidity And Mortality ◽  
Alpha Toxin ◽  
Content Type

ABSTRACT Candida albicans and Staphylococcus aureus are common causes of nosocomial infections with severe morbidity and mortality. Murine polymicrobial intra-abdominal infection (IAI) with C. albicans and S. aureus results in acute mortality dependent on the secreted cytolytic effector alpha-toxin. Here, we confirmed that alpha-toxin is elevated during polymicrobial growth compared to monomicrobial growth in vitro. Therefore, this study sought to unravel the mechanism by which C. albicans drives enhanced staphylococcal alpha-toxin production. Using a combination of functional and genetic approaches, we determined that an intact agr quorum sensing regulon is necessary for enhanced alpha-toxin production during coculture and that a secreted candidal factor likely is not implicated in elevating agr activation. As the agr system is pH sensitive, we observed that C. albicans raises the pH during polymicrobial growth and that this correlates with increased agr activity and alpha-toxin production. Modulation of the pH could predictably attenuate or activate agr activity during coculture. By using a C. albicans mutant deficient in alkalinization (stp2Δ/Δ), we confirmed that modulation of the extracellular pH by C. albicans can drive agr expression and toxin production. Additionally, the use of various Candida species (C. glabrata, C. dubliniensis, C. tropicalis, C. parapsilosis, and C. krusei) demonstrated that those capable of raising the extracellular pH correlated with elevated agr activity and alpha-toxin production during coculture. Overall, we demonstrate that alkalinization of the extracellular pH by the Candida species leads to sustained activation of the staphylococcal agr system. IMPORTANCE Candida albicans and Staphylococcus aureus are commonly coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Thus, they represent a significant cause of nosocomial morbidity and mortality. Yet how these organisms behave in the context of polymicrobial growth remains poorly understood. In this work, we set out to determine the mechanism by which activation of the staphylococcal agr quorum sensing system and production of its major virulence effector alpha-toxin is enhanced during coculture with C. albicans. Surprisingly, we likely ruled out that a secreted candidal factor drives this process. Instead, we demonstrated that alkalinization of the extracellular milieu by C. albicans and other Candida species correlated with elevated agr activity. Thus, we propose a mechanism where modulation of the extracellular pH by fungal opportunists can indirectly alter virulence of a bacterial pathogen. Uncovering molecular events that drive interkingdom pathogenicity mechanisms may enhance surveillance and treatment for devastating polymicrobial infections.

scholarly journals Glyceryl Trinitrate Complements Citrate and Ethanol in a Novel Antimicrobial Catheter Lock Solution To Eradicate Biofilm Organisms

2013 ◽  
Vol 57 (8) ◽  
pp. 3555-3560 ◽  
Author(s):  
Joel Rosenblatt ◽  
Ruth Reitzel ◽  
Tanya Dvorak ◽  
Ying Jiang ◽  
Ray Y. Hachem ◽  
...  
Keyword(s):  
Glyceryl Trinitrate ◽  
Methicillin Resistant ◽  
Content Type ◽  
Lock Solution ◽  
Test Organisms ◽  
History Of ◽  
Lock Therapy ◽  
Catheter Lock ◽  
Clinically Significant

ABSTRACTAntimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistantStaphylococcus aureus, methicillin-resistantStaphylococcus epidermidis,Pseudomonas aeruginosa, andCandida albicansbiofilms in anin vitromodel for catheter biofilm colonization. GTN has a long history of intravenous use as a hypotensive agent. It is potentially attractive as a component of a catheter lock solution because its physiologic half-life is quite short and its metabolic pathways are known. A lock containing 7% citrate and 20% ethanol required 0.01% GTN to fully eradicate biofilms of all test organisms within 2 h in the model. This GTN concentration is below the levels where clinically significant hypotensive effects are expected.

scholarly journals Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Bahgat Z. Gerges ◽  
Nylev Vargas-Cruz ◽  
Issam I. Raad
Keyword(s):  
Therapeutic Option ◽  
Bloodstream Infections ◽  
Central Line ◽  
Emerging Pathogen ◽  
Candida Auris ◽  
Content Type ◽  
Lock Solution ◽  
Highly Effective ◽  
Catheter Lock

ABSTRACT Candida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10 C. auris strains. MEE fully eradicated all C. auris biofilms, while taurolidine lock partially eradicated all of the C. auris biofilms. The superiority was significant for all C. auris strains tested (P = 0.002).

scholarly journals Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque BiofilmsIn Vivo

2014 ◽  
Vol 82 (5) ◽  
pp. 1968-1981 ◽  
Author(s):  
Megan L. Falsetta ◽  
Marlise I. Klein ◽  
Punsiri M. Colonne ◽  
Kathleen Scott-Anne ◽  
Stacy Gregoire ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Bacterial Pathogen ◽  
Single Species ◽  
Content Type ◽  
3 Dimensional ◽  
Biofilm Development

ABSTRACTStreptococcus mutansis often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC).S. mutansmay not act alone;Candida albicanscells are frequently detected along with heavy infection byS. mutansin plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhancedin vitroandin vivo. The presence ofC. albicansaugments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viableS. mutanscells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeableS. mutansmicrocolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Ourin vitrodata also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence withC. albicansinduces the expression of virulence genes inS. mutans(e.g.,gtfB,fabM). We also found thatCandida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease.

scholarly journals Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm FormationIn Vivo

2014 ◽  
Vol 58 (12) ◽  
pp. 7606-7610 ◽  
Author(s):  
Kaat De Cremer ◽  
Nicolas Delattin ◽  
Katrijn De Brucker ◽  
Annelies Peeters ◽  
Soña Kucharíková ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Broad Spectrum ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Candida Krusei ◽  
Content Type ◽  
And Staphylococcus Aureus

ABSTRACTWe here report on thein vitroactivity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, includingCandida albicans,Candida glabrata,Candida dubliniensis,Candida krusei,Pseudomonas aeruginosa,Staphylococcus aureus, andStaphylococcus epidermidis. We validated thein vivoefficacy of orally administered toremifene againstC. albicans and S. aureusbiofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.

scholarly journals In VitroAssessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections

2016 ◽  
Vol 60 (9) ◽  
pp. 5175-5181 ◽  
Author(s):  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Cheryl Hirsh-Ginsberg ◽  
Kimberly Murray ◽  
Anne-Marie Chaftari ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Broad Spectrum ◽  
Clinical Assessment ◽  
Candida Glabrata ◽  
Ethanol Concentration ◽  
Methicillin Resistant ◽  
Content Type ◽  
Lock Solution ◽  
Catheter Lock ◽  
Heparin Lock

ABSTRACTThe rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistantStaphylococcus aureus(MRSA), vancomycin-intermediateStaphylococcus aureus(VISA), methicillin-resistantStaphylococcus epidermidis(MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR)Pseudomonas aeruginosa, MDRKlebsiella pneumoniae, MDREnterobacter cloacae, MDRAcinetobacter baumannii, MDREscherichia coli, MDRStenotrophomonas maltophilia,Candida albicans, andCandida glabratabiofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms ofStaphylococcus aureusandCandida glabrata. The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment.

scholarly journals In Vitro and In Vivo Activity of a Novel Catheter Lock Solution against Bacterial and Fungal Biofilms

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
J. Chandra ◽  
L. Long ◽  
N. Isham ◽  
P. K. Mukherjee ◽  
G. DiSciullo ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Bloodstream Infections ◽  
Central Line ◽  
Resistant Bacteria ◽  
Content Type ◽  
Lock Solution ◽  
Catheter Lock ◽  
Adhesion Phase

ABSTRACT Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using in vitro and in vivo (rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant Enterococcus [VRE]) or fungal (Candida albicans) species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms in vitro after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter; P = 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment; P = 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms in vivo on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi in vitro and in vivo.

scholarly journals Activity of Daptomycin with or without 25 Percent Ethanol Compared to Combinations of Minocycline, EDTA, and 25 Percent Ethanol against Methicillin-Resistant Staphylococcus aureus Isolates Embedded in Biofilm

2013 ◽  
Vol 57 (4) ◽  
pp. 1998-2000 ◽  
Author(s):  
R. Estes ◽  
J. Theusch ◽  
A. Beck ◽  
D. Pitrak ◽  
Kathleen M. Mullane
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bloodstream Infections ◽  
Central Line ◽  
Methicillin Resistant ◽  
Content Type ◽  
Lock Therapy ◽  
Antibiotic Lock ◽  
Mrsa Colonization

ABSTRACTCentral venous catheters commonly develop central line-associated bloodstream infections.In vitroantibiotic lock therapy (ALT) was simulated on 10 methicillin-resistantStaphylococcus aureus(MRSA) clinical isolates imbedded in biofilm-coated silicon disks. Five days of 4-h daily exposures to daptomycin (2.5 mg/ml) in 25% ethanol or minocycline (3 mg/ml) plus 25% ethanol and 30 mg/ml EDTA resulted in significantly greater elimination of MRSA colonization than treatment with minocycline alone.

scholarly journals Liposomal Amphotericin B Displays Rapid Dose-Dependent Activity against Candida albicans Biofilms

2013 ◽  
Vol 57 (5) ◽  
pp. 2369-2371 ◽  
Author(s):  
Gordon Ramage ◽  
Anto Jose ◽  
Leighann Sherry ◽  
David F. Lappin ◽  
Brian Jones ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Liposomal Amphotericin ◽  
Clinical Problem ◽  
Dependent Manner ◽  
Content Type ◽  
Attractive Option ◽  
Important Clinical Problem ◽  
Lock Therapy ◽  
Catheter Lock ◽  
Dose Dependent

ABSTRACTBiofilms formed byCandida albicansbloodstream isolates on catheters are an important clinical problem. Devising chemotherapeutic strategies to treat thesein situis an attractive option. We report here that liposomal amphotericin effectively killsC. albicansbiofilms rapidly (12 h) and effectively (>90%) in a dose-dependent manner, whereas caspofungin displays an inverse concentration-dependent effect. This study has implications for considering the effective doses of antifungal agents used for catheter lock therapy.

scholarly journals Modulation of Staphylococcus aureus Response to Antimicrobials by the Candida albicans Quorum Sensing Molecule Farnesol

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Eric F. Kong ◽  
Christina Tsui ◽  
Sona Kucharíková ◽  
Patrick Van Dijck ◽  
Mary Ann Jabra-Rizk
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Quorum Sensing ◽  
Physiological Role ◽  
Efflux Pumps ◽  
Content Type ◽  
The Impact ◽  
Quorum Sensing Molecule

ABSTRACT In microbial biofilms, microorganisms utilize secreted signaling chemical molecules to coordinate their collective behavior. Farnesol is a quorum sensing molecule secreted by the fungal species Candida albicans and shown to play a central physiological role during fungal biofilm growth. Our pervious in vitro and in vivo studies characterized an intricate interaction between C. albicans and the bacterial pathogen Staphylococcus aureus, as these species coexist in biofilm. In this study, we aimed to investigate the impact of farnesol on S. aureus survival, biofilm formation, and response to antimicrobials. The results demonstrated that in the presence of exogenously supplemented farnesol or farnesol secreted by C. albicans in biofilm, S. aureus exhibited significantly enhanced tolerance to antimicrobials. By using gene expression studies, S. aureus mutant strains, and chemical inhibitors, the mechanism for the enhanced tolerance was attributed to upregulation of drug efflux pumps. Importantly, we showed that sequential exposure of S. aureus to farnesol generated a phenotype of high resistance to antimicrobials. Based on the presence of intracellular reactive oxygen species upon farnesol exposure, we hypothesize that antimicrobial tolerance in S. aureus may be mediated by farnesol-induced oxidative stress triggering the upregulation of efflux pumps, as part of a general stress response system. Hence, in mixed biofilms, C. albicans may influence the pathogenicity of S. aureus through acquisition of a drug-tolerant phenotype, with important therapeutic implications. Understanding interspecies signaling in polymicrobial biofilms and the specific drug resistance responses to secreted molecules may lead to the identification of novel targets for drug development.

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