Parenteral Lipid Emulsion Induces Germination of<i>Candida albicans</i>and Increases Biofilm Formation on Medical Catheter Surfaces

Swindell, Kim; Lattif, Ali Abdul; Chandra, Jyotsna; Mukherjee, Pranab K.; Ghannoum, Mahmoud A.

doi:10.1086/600106

Cited by 54 publications

(46 citation statements)

References 42 publications

(54 reference statements)

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“…The clinical C. albicans wild-type strain SC5314 (a clinical isolate originally obtained from a patient with disseminated candidiasis [37]) was used in all experiments as a control standard. This strain was selected because it can form robust biofilms and is well characterized genetically (38). In addition, 12 C. albicans clinical isolates resistant to fluconazole by overexpression of drug efflux pumps and/or with mutations in the azole target gene ERG11 (34,35) (Table 1) were used, together with C. albicans mutant strains with mutations in selected transcription factors developed by Homann and coworkers (36) (see Table S1 in the supplemental material).…”

Section: Methodsmentioning

confidence: 99%

In Vitro Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral Candidiasis

Vila

Chaturvedi

Rozental

et al. 2015

Antimicrob Agents Chemother

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The generation of a new antifungal against Candida albicans biofilms has become a major priority, since biofilm formation by this opportunistic pathogenic fungus is usually associated with an increased resistance to azole antifungal drugs and treatment failures. Miltefosine is an alkyl phospholipid with promising antifungal activity. Here, we report that, when tested under planktonic conditions, miltefosine displays potent in vitro activity against multiple fluconazole-susceptible and -resistant C. albicans clinical isolates, including isolates overexpressing efflux pumps and/or with well-characterized Erg11 mutations. Moreover, miltefosine inhibits C. albicans biofilm formation and displays activity against preformed biofilms. Serial passage experiments confirmed that miltefosine has a reduced potential to elicit resistance, and screening of a library of C. albicans transcription factor mutants provided additional insight into the activity of miltefosine against C. albicans growing under planktonic and biofilm conditions. Finally, we demonstrate the in vivo efficacy of topical treatment with miltefosine in the murine model of oropharyngeal candidiasis. Overall, our results confirm the potential of miltefosine as a promising antifungal drug candidate, in particular for the treatment of azole-resistant and biofilm-associated superficial candidiasis.T he recent elevated incidence of fungal infections is related to the indiscriminate use of broad-spectrum antibiotics and corticosteroids, the increase in the number of invasive medical procedures, and the AIDS epidemic. The persistence of these infections is usually associated with the fungal ability to form biofilms on implantable medical devices (1). Candida spp. can adhere and form biofilms on the surface of different medical devices (such as catheters, prostheses, pacemakers, and heart valves) and on the mucosal surface, leading to a superficial infection with a complex structure in which hyphae, pseudohyphae, and yeasts grow surrounded by a dense extracellular matrix, composed mainly of proteins, polysaccharides, and extracellular DNA (eDNA) (2). Hematogenous dissemination may occur due to the detachment of yeasts from the top layer of the biofilm, a phenomenon known as dispersion (3). Candida albicans is the third leading cause of infections related to the use of catheters (4, 5). Development of candidemia during hospitalization when central venous catheters are used can happen in 72% of cases in Latin America (6), and the worldwide mortality rate for catheter-related candidemia can reach 41% (7). Oropharyngeal candidiasis (OPC) is characterized by Candida growth as a biofilm over the tongue and oral mucosa. OPC has been described as the most frequent opportunistic fungal infection among HIV-positive patients, and it is estimated that more than 90% of these patients develop this infection at some time during the progression of their disease (8, 9).The increased resistance to antifungal agents is the main clinical complication associated with biofilm formation. ...

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Section: Methodsmentioning

confidence: 99%

In Vitro Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral Candidiasis

Vila

Chaturvedi

Rozental

et al. 2015

Antimicrob Agents Chemother

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“…It has been reported that certain Candida species in the presence of glucose-containing fluids or lipid emulsion might produce ''slime'' (now commonly referred to as biofilm), potentially explaining the increased proportion of CBSIs among patients receiving parenteral nutrition [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes mellitus has previously been reported to be a general risk factor for Candida infections [22]. Yet, glucose is thought to serve as the carbohydrate energy source required by Candida for biofilm formation [25], perhaps necessary to produce the polysaccharide matrix [27], in which organized communities of yeast, hyphae, and pseudohyphae are enclosed [28]. In a study by Bhatt et al [29] they reported administration of broad spectrum antibiotics, indwelling catheter and patients on mechanically ventilator were the major risk factor.…”

Section: Discussionmentioning

confidence: 99%

Detection of biofilm production in Candida species isolates recovered from bloodstream patients

Pal¹,

Bisht²

2016

Int J of Biomed & Adv Res

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Introduction: Candida Bloodstream Infections (CBSIs) are the fourth most common infections among hospitalized patients. Candida biofilm results from an initial attachment of cells to glycoprotein-coated host cells and tissue or biomaterial surfaces. Material and Method: Candida spp. was identified by conventional method and biofilm formation was detected by tube method. Result: C. tropicalis was the most common species followed by C. haemulonii, C. albicans, C. parapsilosis, C. glabrata, C. pelliculosa, C. guilliermondii and C. krusei. 125 of the isolates were tested for biofilm formation of which 67(53.6%) were found to be capable of forming biofilms. Of these 55(82%) biofilm forming isolates were those recovered from patients with Catheter Related Candidemia (CRC) while 12 (17.9%) biofilm forming isolates were without CRC. Most common biofilm producing species were C.pelliculosa followed by C.tropicalis, C.haemulonii, C. parapsilosis, C.glabrata, C. albicans, C.krusei and C. guilliermondii. Conclusion: Our study found more biofilm production in Central Venous Catheter (CVC) Candidemia and most of the CVC related Candidemia were found in diabetic and neutropenic patients and hence care should be taken in those patients who are at risk of developing biofilm production before applying the external appliances.

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“…Treated cells were examined using confocal scanning laser microscopy (2). Germination of C. albicans strains in the presence of different concentrations of GV (0.5ϫ to 5ϫ the individual MIC of each isolate) was compared to that of cells exposed to fetal bovine serum (FBS) (HyClone, Logan, UT), a known inducer of germination (7).…”

mentioning

confidence: 99%

Gentian Violet Exhibits Activity against Biofilms Formed by Oral Candida Isolates Obtained from HIV-Infected Patients

Traboulsi

Mukherjee

Chandra

et al. 2011

Antimicrob Agents Chemother

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The effect of gentian violet against Candida albicans and non-Candida albicans biofilms formed on polymethylmethacrylate strips was evaluated using a dry weight assay and confocal laser scanning microscopy. The ability of gentian violet to inhibit Candida albicans germination was also assessed. Gentian violet activity against Candida biofilms was demonstrated by a reduction in dry weight, disruption of biofilm architecture, and reduced biofilm thickness. Additionally, gentian violet inhibited Candida germination in a concentrationdependent manner.

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Parenteral Lipid Emulsion Induces Germination ofCandida albicansand Increases Biofilm Formation on Medical Catheter Surfaces

Abstract: LE-inducible candidal virulence determinants, such as germination and enhanced biofilm production, may help to explain the increased risk of candidemia in patients receiving LE via medical catheters.

Cited by 54 publications

References 42 publications

In Vitro Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral Candidiasis

In Vitro Activity of Miltefosine against Candida albicans under Planktonic and Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral Candidiasis

Detection of biofilm production in Candida species isolates recovered from bloodstream patients

Gentian Violet Exhibits Activity against Biofilms Formed by Oral Candida Isolates Obtained from HIV-Infected Patients

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