In Vitro Activity of Novel Lipopeptides against Triazole-Resistant Aspergillus fumigatus

被引:3
作者
Fioriti, Simona [1 ]
Cirioni, Oscar [1 ,2 ]
Simonetti, Oriana [3 ]
Franca, Lucia [1 ,4 ]
Candelaresi, Bianca [1 ,2 ]
Pallotta, Francesco [1 ,2 ]
Neubauer, Damian [5 ]
Kamysz, Elzbieta [6 ]
Kamysz, Wojciech [5 ]
Canovari, Benedetta [4 ]
Brescini, Lucia [1 ,2 ]
Morroni, Gianluca [1 ]
Barchiesi, Francesco [1 ,4 ]
机构
[1] Polytech Univ Marche, Dept Biomed Sci & Publ Hlth, I-60126 Ancona, Italy
[2] Azienda Osped Univ Osped Riuniti, Infect Dis Clin, I-60126 Ancona, Italy
[3] Polytech Univ Marche, Dept Clin & Mol Sci, Dermatol Unit, I-60126 Ancona, Italy
[4] Azienda Osped Osped Riuniti Marche Nord, Infect Dis Unit, I-61122 Pesaro, Italy
[5] Med Univ Gdansk, Fac Pharm, Dept Inorgan Chem, PL-80210 Gdansk, Poland
[6] Univ Gdansk, Fac Chem, Dept Mol Biotechnol, Lab Chem Biol Macromol, PL-80309 Gdansk, Poland
关键词
Aspergillus fumigatus; azole resistance; antimicrobial peptides; lipopeptides; ANTIFUNGAL AGENTS; EPIDEMIOLOGY; COMBINATION; MECHANISMS; DIAGNOSIS;
D O I
10.3390/jof8080872
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Aspergillosis, which is mainly sustained by Aspergillus fumigatus, includes a broad spectrum of diseases. They are usually severe in patients with co-morbidities. The first-line therapy includes triazoles, for which an increasing incidence of drug resistance has been lately described. As a consequence of this, the need for new and alternative antifungal molecules is absolutely necessary. As peptides represent promising antimicrobial molecules, two lipopeptides (C14-NleRR-NH2, C14-WRR-NH2) were tested to assess the antifungal activity against azole-resistant A. fumigatus. Antifungal activity was evaluated by determination of minimum inhibitory concentrations (MICs), time-kill curves, XTT assay, optical microscopy, and checkerboard combination with isavuconazole. Both lipopeptides showed antifungal activity, with MICs ranging from 8 mg/L to 16 mg/L, and a dose-dependent effect was confirmed by both time-kill curves and XTT assays. Microscopy showed that hyphae growth was hampered at concentrations equal to or higher than MICs. The rising antifungal resistance highlights the usefulness of novel compounds to treat severe fungal infections. Although further studies assessing the activity of lipopeptides are necessary, these molecules could be effective antifungal alternatives that overcome the current resistances.
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页数:10
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共 33 条
  • [11] Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields
    Huan, Yuchen
    Kong, Qing
    Mou, Haijin
    Yi, Huaxi
    [J]. FRONTIERS IN MICROBIOLOGY, 2020, 11
  • [12] DAPTOMYCIN, its membrane-active mechanism vs. that of other antimicrobial peptides
    Huang, Huey W.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2020, 1862 (10):
  • [13] Invasive aspergillosis in critically ill patients: Review of definitions and diagnostic approaches
    Jenks, Jeffrey D.
    Nam, Hannah H.
    Hoenigl, Martin
    [J]. MYCOSES, 2021, 64 (09) : 1002 - 1014
  • [14] In vitro activity of the lipopeptide PAL-Lys-Lys-NH2, alone and in combination with antifungal agents, against clinical isolates of Candida spp.
    Kamysz, E.
    Simonetti, O.
    Cirioni, O.
    Arzeni, D.
    Ganzetti, G.
    Campanati, A.
    Giacometti, A.
    Gabrielli, E.
    Silvestri, C.
    Kamysz, W.
    Offidani, A.
    Barchiesi, F.
    [J]. PEPTIDES, 2011, 32 (01) : 99 - 103
  • [15] Aspergillus fumigatus and Aspergillosis in 2019
    Latge, Jean-Paul
    Chamilos, Georgios
    [J]. CLINICAL MICROBIOLOGY REVIEWS, 2020, 33 (01)
  • [16] Ultrashort antibacterial and antifungal lipopeptides
    Makovitzki, Arik
    Avrahami, Dorit
    Shai, Yechiel
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (43) : 15997 - 16002
  • [17] Lipopeptides as the Antifungal and Antibacterial Agents: Applications in Food Safety and Therapeutics
    Meena, Khem Raj
    Kanwar, Shamsher S.
    [J]. BIOMED RESEARCH INTERNATIONAL, 2015, 2015
  • [18] Antimicrobial host defence peptides: functions and clinical potential
    Mookherjee, Neeloffer
    Anderson, Marilyn A.
    Haagsman, Henk P.
    Davidson, Donald J.
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2020, 19 (05) : 311 - 332
  • [19] Ultrashort Cationic Lipopeptides-Effect of N-Terminal Amino Acid and Fatty Acid Type on Antimicrobial Activity and Hemolysis
    Neubauer, Damian
    Jaskiewicz, Maciej
    Bauer, Marta
    Golacki, Krzysztof
    Kamysz, Wojciech
    [J]. MOLECULES, 2020, 25 (02):
  • [20] Synergy, antagonism, and what the chequerboard puts between them
    Odds, FC
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2003, 52 (01) : 1 - 1