Endocytosis-Mediated Vacuolar Accumulation of the Human ApoE Apolipoprotein-Derived ApoEdpL-W Antimicrobial Peptide Contributes to Its Antifungal Activity in Candida albicans

Rossignol, Tristan; Kelly, Bridie A.; Dobson, Curtis B.; d’Enfert, Christophe

doi:10.1128/aac.00319-11

Cited by 43 publications

(22 citation statements)

References 68 publications

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“…In contrast, compounds 1–4 , 6 , 8 and 19–21 displayed appreciable antifungal activity against the different yeast species (MIC 90 s ranging from 0.8 to 12.5 µg/mL). However, MIC 90 s were significantly higher for C. glabrata than for other yeast species which was in agreement with previous observations showing decreased sensitivity of C. glabrata to antifungals such as azoles and the antifungal peptide ApoEdpL-W [1], [14], [15], [16], [17]. Compound 6 and compounds with seven-membered saturated rings ( 19 and 20 ) showed reduced activity towards C. parapsilosis .…”

Section: Resultssupporting

confidence: 91%

“…The concentration, purity, and integrity of the isolated RNA were evaluated using a Nanodrop spectrophotometer (Thermo Fisher, Illkirch, France) and an Agilent 2100 Bioanalyzer (Agilent Technologies, Waldbronn, Germany). cDNA synthesis, labeling and hybridization on C. albicans oligonucleotide microarrays (Eurogentec, Liege, Belgium) were performed as described in Rossignol et al [14]. Sample comparisons at 30 and 60 min were performed on two biological replicates, and each biological replicate was subjected to technical replicates with dye swap.…”

Section: Methodsmentioning

confidence: 99%

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Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans

et al. 2013

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We investigated the antifungal activity of fused Mannich ketone (FMK) congeners and two of their aminoalcohol derivatives. In particular, FMKs with five-membered saturated rings were shown to have minimum inhibitory concentration (MIC90s) ranging from 0.8 to 6 µg/mL toward C. albicans and the closely related C. parapsilosis and C. krusei while having reduced efficacy toward C. glabrata and almost no efficacy against Aspergillus sp. Transcript profiling of C. albicans cells exposed for 30 or 60 min to 2-(morpholinomethyl)-1-indanone, a representative FMK with a five-membered saturated ring, revealed a transcriptional response typical of oxidative stress and similar to that of a C. albicans Cap1 transcriptional activator. Consistently, C. albicans lacking the CAP1 gene was hypersensitive to this FMK, while C. albicans strains overexpressing CAP1 had decreased sensitivity to 2-(morpholinomethyl)-1-indanone. Quantitative structure–activity relationship studies revealed a correlation of antifungal potency and the energy of the lowest unoccupied molecular orbital of FMKs and unsaturated Mannich ketones thereby implicating redox cycling-mediated oxidative stress as a mechanism of action. This conclusion was further supported by the loss of antifungal activity upon conversion of representative FMKs to aminoalcohols that were unable to participate in redox cycles.

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Section: Resultssupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans

et al. 2013

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“…Rossignol et al (2011) studied the 18-amino acid cationic, tryptophan-rich, ApoEdpL-W peptide, derived from human ApoE apolipoprotein, which was shown to have antifungal activity against pathogenic yeasts of the Candida genus (except C. glabrata). ApoEdpL-W was active against planktonic cells and early-stage biofilms but less active against mature biofilms, possibly because of its affinity for extracellular matrix b-glucans.…”

Section: Candida Biofilm and New Antifungal Strategiesmentioning

confidence: 99%

Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

Sardi

Scorzoni

Bernardi

et al. 2013

Journal of Medical Microbiology

1,049

825

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“…The original ApoEdp peptide (sequence, LRKLRKRLLLRKLRKRLL) showed direct, broad anti-infective activity against bacteria and viruses (27). Replacement of all leucine residues with tryptophan amino acids in ApoEdpL-W (sequence, WRKWRKRWWWRKWRK RWW) led to production of a variant with increased potency and high antimicrobial activity against viruses, parasites, and Staphylococcus aureus, despite a slight decrease of antibacterial activity against Pseudomonas aeruginosa (28)(29)(30). To identify bacterial resistance potentially induced upon exposure to antimicrobial peptides, we studied the Escherichia coli genetic response to ApoEdpL-W and demonstrated the contribution of the CpxAR envelope stress signaling pathway to E. coli resistance to ApoEdpL-W and several other antimicrobial peptides.…”

mentioning

confidence: 99%

Induction of the Cpx Envelope Stress Pathway Contributes to Escherichia coli Tolerance to Antimicrobial Peptides

Audrain

Ferrières

Zaïri

et al. 2013

Appl Environ Microbiol

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e Antimicrobial peptides produced by multicellular organisms as part of their innate system of defense against microorganisms are currently considered potential alternatives to conventional antibiotics in case of infection by multiresistant bacteria. However, while the mode of action of antimicrobial peptides is relatively well described, resistance mechanisms potentially induced or selected by these peptides are still poorly understood. In this work, we studied the mechanisms of action and resistance potentially induced by ApoEdpL-W, a new antimicrobial peptide derived from human apolipoprotein E. Investigation of the genetic response of Escherichia coli upon exposure to sublethal concentrations of ApoEdpL-W revealed that this antimicrobial peptide triggers activation of RcsCDB, CpxAR, and E envelope stress pathways. This genetic response is not restricted to ApoEdpL-W, since several other antimicrobial peptides, including polymyxin B, melittin, LL-37, and modified S 4 dermaseptin, also activate several E. coli envelope stress pathways. Finally, we demonstrate that induction of the CpxAR two-component system directly contributes to E. coli tolerance toward ApoEdpL-W, polymyxin B, and melittin. These results therefore show that E. coli senses and responds to different antimicrobial peptides by activation of the CpxAR pathway. While this study further extends the understanding of the array of peptide-induced stress signaling systems, it also provides insight into the contribution of Cpx envelope stress pathway to E. coli tolerance to antimicrobial peptides.

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Endocytosis-Mediated Vacuolar Accumulation of the Human ApoE Apolipoprotein-Derived ApoEdpL-W Antimicrobial Peptide Contributes to Its Antifungal Activity in Candida albicans

Abstract: The 18-amino-acid cationic, tryptophan-rich ApoEdpL-W peptide derived from human ApoE apolipoprotein was shown to have antifungal activity against pathogenic yeasts of the Candida genus (except C. glabrata).

Cited by 43 publications

References 68 publications

Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans

Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans

Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

Induction of the Cpx Envelope Stress Pathway Contributes to Escherichia coli Tolerance to Antimicrobial Peptides

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