Synergistic Activity of the Plant Defensin HsAFP1 and Caspofungin against Candida albicans Biofilms and Planktonic Cultures

Vriens, Kim; Cools, Tanne; Harvey, Peta J.; Craik, David J.; Spincemaille, Pascal; Cassiman, David; Braem, Annabel; Zhang, Fei; Nibbering, Peter H.; Drijfhout, Jan W.; Coninck, Barbara De; Cammue, Bruno P. A.; Thevissen, Karin

doi:10.1371/journal.pone.0132701

Cited by 67 publications

(77 citation statements)

References 82 publications

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“…In that study, recombinant HsAFP1 was shown to act synergistically with caspofungin in the prevention and eradication of C. albicans biofilms [53]. Such synergistic antibiofilm activities between plant defensins and conventional antimycotics are not defensin-specific.…”

Section: Discussionmentioning

confidence: 92%

“…We recently reported on the antibiofilm activity of another plant defensin, HsAFP1, which can inhibit C. albicans biofilm formation, but cannot eradicate C. albicans biofilms [53]. In that study, recombinant HsAFP1 was shown to act synergistically with caspofungin in the prevention and eradication of C. albicans biofilms [53].…”

Section: Discussionmentioning

confidence: 98%

“…rRsAFP2 was produced in P. pastoris and purified by cation exchange chromatography and reversed-phase chromatography, following the protocol previously described for production and purification of rHsAFP1 [53] with minor modifications: P. pastoris strain GS115 was used for expression of rRsAFP2 and induction of gene expression was performed for 72 h at 25 • C, during which 2% methanol (v/v%) was added to the culture every 24 h to maintain induction. In addition, an automated peristaltic pump (Spectrum Laboratories, CA, USA) and a Vivaflow 200 cassette with a 2-kDa cut-off Hydrosart membrane (Invitrogen, CA, USA) were used for ultrafiltration.…”

Section: Production and Purification Of Recombinant (R) Rrsafp2mentioning

confidence: 99%

“…However, a multidrug approach can be used to improve the efficacy of these antimycotics against biofilm-associated infections, which are often difficult to treat [35]. In view of the latter, we recently reported on the potential of the recombinant HsAFP1 defensin to act synergistically with these antimycotics in the prevention and eradication of C. albicans biofilms at concentrations that are 10-to 200-fold lower than its BIC-2 and BEC-2, respectively [53]. Therefore, in this study, we assessed the potential synergistic activity between rRsAFP2 and caspofungin or amphotericin B against C. albicans biofilms.…”

Section: Rrsafp2 Acts Synergistically With Caspofungin Against Candidmentioning

confidence: 99%

“…These biofilms are highly resistant towards most conventional antimycotics, with few exceptions, including miconazole, caspofungin, anidulafungin, and liposomal formulations of amphotericin B [18,19,22,40]. Recently, we found that the coral bells defensin HsAFP1 prevents C. albicans biofilm formation and increases caspofungin's activity against C. albicans biofilms [53].…”

Section: Introductionmentioning

confidence: 99%

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The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms

et al. 2016

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The radish defensin RsAFP2 was previously characterized as a peptide with potent antifungal activity against several plant pathogenic fungi and human pathogens, including Candida albicans. RsAFP2 induces apoptosis and impairs the yeast-to-hypha transition in C. albicans. As the yeast-to-hypha transition is considered important for progression to mature biofilms, we analyzed the potential antibiofilm activity of recombinant (r)RsAFP2, heterologously expressed in Pichia pastoris, against C. albicans biofilms. We found that rRsAFP2 prevents C. albicans biofilm formation with a BIC-2 (i.e., the minimal rRsAFP2 concentration that inhibits biofilm formation by 50% as compared to control treatment) of 1.65 ± 0.40 mg/mL. Moreover, biofilm-specific synergistic effects were observed between rRsAFP2 doses as low as 2.5 μg/mL to 10 μg/mL and the antimycotics caspofungin and amphotericin B, pointing to the potential of RsAFP2 as a novel antibiofilm compound. In addition, we characterized the solution structure of rRsAFP2 and compared it to that of RsAFP1, another defensin present in radish seeds. These peptides have similar amino acid sequences, except for two amino acids, but rRsAFP2 is more potent than RsAFP1 against planktonic and biofilm cultures. Interestingly, as in case of rRsAFP2, also RsAFP1 acts synergistically with caspofungin against C. albicans biofilms in a comparable low dose range as rRsAFP2. A structural comparison of both defensins via NMR analysis revealed that also rRsAFP2 adopts the typical cysteine-stabilized αβ-motif of plant defensins, however, no structural differences were found between these peptides that might result in their differential antifungal/antibiofilm potency. This further suggests that the conserved structure of RsAFP1 and rRsAFP2 bears the potential to synergize with antimycotics against C. albicans biofilms.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Production and Purification Of Recombinant (R) Rrsafp2mentioning

confidence: 99%

Section: Rrsafp2 Acts Synergistically With Caspofungin Against Candidmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms

et al. 2016

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Therapeutic Options for Treatment of Infections by Pathogenic Biofilms

Costa

Franco

2019

Antibiotic Drug Resistance

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Antimicrobial Peptide Synergies for Fighting Infectious Diseases

et al. 2023

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Antimicrobial peptides (AMPs) are essential elements of thehost defense system. Characterized by heterogenous structures and broad‐spectrumaction, they are promising candidates for combating multidrug resistance. Thecombined use of AMPs with other antimicrobial agents provides a new arsenal ofdrugs with synergistic action, thereby overcoming the drawback of monotherapiesduring infections. AMPs kill microbes via pore formation, thus inhibitingintracellular functions. This mechanism of action by AMPs is an advantage overantibiotics as it hinders the development of drug resistance. The synergisticeffect of AMPs will allow the repurposing of conventional antimicrobials andenhance their clinical outcomes, reduce toxicity, and, most significantly,prevent the development of resistance. In this review, various synergies ofAMPs with antimicrobials and miscellaneous agents are discussed. The effect ofstructural diversity and chemical modification on AMP properties is firstaddressed and then different combinations that can lead to synergistic action,whether this combination is between AMPs and antimicrobials, or AMPs andmiscellaneous compounds, are attended. This review can serve as guidance whenredesigning and repurposing the use of AMPs in combination with other antimicrobialagents for enhanced clinical outcomes.

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Synergistic Activity of the Plant Defensin HsAFP1 and Caspofungin against Candida albicans Biofilms and Planktonic Cultures

Cited by 67 publications

References 82 publications

The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms

The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms

Therapeutic Options for Treatment of Infections by Pathogenic Biofilms

Antimicrobial Peptide Synergies for Fighting Infectious Diseases

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