In Vitro Activities of Anidulafungin and Other Antifungal Agents against Biofilms Formed by Clinical Isolates of Different Candida and Aspergillus Species

Fiori, Barbara; Posteraro, Brunella; Torelli, Riccardo; Tumbarello, Mario; Perlin, David S.; Fadda, Giovanni

doi:10.1128/aac.01569-10

Cited by 68 publications

(56 citation statements)

References 27 publications

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“…Biofilms formed by C. albicans cells usually increase resistance to commonly used antifungal drugs, such as azoles and amphotericin B (Walker et al ., 2010; Fiori et al ., 2011). It is important to develop new antifungal drugs that efficiently control biofilm formation.…”

Section: Discussionmentioning

confidence: 99%

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

Zhao

Huang

Sun

et al. 2018

Microbial Biotechnology

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SummaryClinical treatment of Candida albicans infections has become more difficult due to the limited development of antifungal agents and the rapid emergence of drug resistance. In this study, we demonstrate the synthesis of a series of piperazine derivatives and the evaluation of their inhibitory activity against C. albicans virulence. Thirty‐four (1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives, including 25 new compounds, were synthesized and assessed for their efficacy against the physiology and pathogenesis of C. albicans. Several compounds strongly inhibited the morphological transition and virulence of C. albicans cells, although they did not influence the growth rate of the fungal pathogen. A leading novel compound, (1‐(4‐ethoxyphenyl)‐4‐(1‐biphenylol‐2‐hydroxypropyl)‐piperazine), significantly attenuated C. albicans virulence by interfering with the process of hyphal development, but it showed no cytotoxicity against human cells at a micromolar level. These findings suggest that (1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives could potentially be developed as novel therapeutic agents for the clinical treatment of C. albicans infections by interfering with morphological transition and virulence.

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Section: Discussionmentioning

confidence: 99%

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

Zhao

Huang

Sun

et al. 2018

Microbial Biotechnology

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“…All the isolates were retrieved from their frozen glycerol stocks and were streaked on fresh Sabouraud dextrose agar (Kima, Padua, Italy) plates, until good sporulation was achieved following incubation at 37°C. For all experiments, conidial suspensions in RPMI 1640 medium (Sigma-Aldrich, Milan, Italy) were obtained as described elsewhere (12,28) and used to prepare the inocula (see below).…”

Section: Methodsmentioning

confidence: 99%

“…This growth phenotype, which complies with the definition of a biofilm (10), may help A. fumigatus to colonize the host substratum and to resist phagocytic and antimicrobial attacks, mimicking the typical Candida albicans or bacterial biofilm (8,11). Recent observations have consistently shown that all antifungal drugs are significantly less effective when A. fumigatus is grown as a biofilm than when it is grown in the planktonic state (4,7,9,12,13), presumably as a reflection of multiple resistance mechanisms, including the ECM, which would prevent drug diffusion by acting as a physical barrier (14). This could contribute to the overall mortality with invasive aspergillosis, which remains high, despite the use of newer broad-spectrum antifungal agents and diagnostic adjuncts (15).…”

mentioning

confidence: 99%

In Vitro Interaction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

Bugli

Posteraro

Papi

et al. 2013

Antimicrob Agents Chemother

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Aspergillus fumigatus biofilms represent a problematic clinical entity, especially because of their recalcitrance to antifungal drugs, which poses a number of therapeutic implications for invasive aspergillosis, the most difficult-to-treat Aspergillus-related disease. While the antibiofilm activities of amphotericin B (AMB) deoxycholate and its lipid formulations (e.g., liposomal AMB [LAMB]) are well documented, the effectiveness of these drugs in combination with nonantifungal agents is poorly understood. In the present study, in vitro interactions between polyene antifungals (AMB and LAMB) and alginate lyase (AlgL), an enzyme degrading the polysaccharides produced as extracellular polymeric substances (EPSs) within the biofilm matrix, against A. fumigatus biofilms were evaluated by using the checkerboard microdilution and the time-kill assays. Furthermore, atomic force microscopy (AFM) was used to image and quantify the effects of AlgL-antifungal combinations on biofilm-growing hyphal cells. On the basis of fractional inhibitory concentration index values, synergy was found between both AMB formulations and AlgL, and this finding was also confirmed by the time-kill test. Finally, AFM analysis showed that when A. fumigatus biofilms were treated with AlgL or polyene alone, as well as with their combination, both a reduction of hyphal thicknesses and an increase of adhesive forces were observed compared to the findings for untreated controls, probably owing to the different action by the enzyme or the antifungal compounds. Interestingly, marked physical changes were noticed in A. fumigatus biofilms exposed to the AlgL-antifungal combinations compared with the physical characteristics detected after exposure to the antifungals alone, indicating that AlgL may enhance the antibiofilm activity of both AMB and LAMB, perhaps by disrupting the hypha-embedding EPSs and thus facilitating the drugs to reach biofilm cells. Taken together, our results suggest that a combination of AlgL and a polyene antifungal may prove to be a new therapeutic strategy for invasive aspergillosis, while reinforcing the EPS as a valuable antibiofilm drug target.

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“…Echinocandins are fungicidal for Candida planktonic cells (nonattached cells) and exhibit activity against mature biofilms of several Candida species (13)(14)(15)(16)(17). There have been several studies on the efficacy of echinocandins against Candida biofilms (18)(19)(20)(21), the occurrence of the paradoxical effect observed with this class of antifungals (22,23), and the role of echinocandin lock solutions in the management of candidiasis related to implanted devices (24); however, there are no comprehensive reports that have compared the in vitro activities of the three echinocandins against biofilms formed by different non-albicans Candida spp. The aim of this study was to determine the antifungal activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells as well as biofilms formed by non-C. albicans Candida bloodstream isolates, such as C. parapsi-losis, C. krusei, C. lusitaniae, and C. guilliermondii, in comparison to those of C. albicans.…”

mentioning

confidence: 99%

Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates

Simitsopoulou

Peshkova

Tasina

et al. 2013

Antimicrob Agents Chemother

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e Candida species other than Candida albicans are increasingly recognized as causes of biofilm-associated infections. This is a comprehensive study that compared the in vitro activities of all three echinocandins against biofilms formed by different common and infrequently identified Candida isolates. We determined the activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells and biofilms of bloodstream isolates of C. albicans (15 strains), Candida parapsilosis (6 strains), Candida lusitaniae (16 strains), Candida guilliermondii (5 strains), and Candida krusei (12 strains) by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. Planktonic and biofilm MICs were defined as >50% fungal damage. Planktonic cells of all Candida species were susceptible to the three echinocandins, with MICs of <1 mg/liter. By comparison, differences in the MIC profiles of biofilms in response to echinocandins existed among the Candida species. Thus, C. lusitaniae and C. guilliermondii biofilms were highly recalcitrant to all echinocandins, with MICs of >32 mg/ liter. In contrast, the MICs of all three echinocandins for C. albicans and C. krusei biofilms were relatively low (MICs < 1 mg/ liter). While echinocandins exhibited generally high MICs against C. parapsilosis biofilms, MFG exhibited the lowest MICs against these isolates (4 mg/liter). A paradoxical growth effect was observed with CAS concentrations ranging from 8 to 64 mg/ liter against C. albicans and C. parapsilosis biofilms but not against C. krusei, C. lusitaniae, or C. guilliermondii. While nonalbicans Candida planktonic cells were susceptible to all echinocandins, there were drug-and species-specific differences in susceptibility among biofilms of the various Candida species, with C. lusitaniae and C. guilliermondii exhibiting profiles of high MICs of the three echinocandins.

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In Vitro Activities of Anidulafungin and Other Antifungal Agents against Biofilms Formed by Clinical Isolates of Different Candida and Aspergillus Species

Cited by 68 publications

References 27 publications

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

In Vitro Interaction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates

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