Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 18;8(8):872.
doi: 10.3390/jof8080872.

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

Simona Fioriti  1 , Oscar Cirioni  1   2 , Oriana Simonetti  3 , Lucia Franca  1   4 , Bianca Candelaresi  1   2 , Francesco Pallotta  1   2 , Damian Neubauer  5 , Elzbieta Kamysz  6 , Wojciech Kamysz  5 , Benedetta Canovari  4 , Lucia Brescini  1   2 , Gianluca Morroni  1 , Francesco Barchiesi  1   4
Affiliations

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

Simona Fioriti et al. J Fungi (Basel). .

Abstract

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.

Keywords: Aspergillus fumigatus; antimicrobial peptides; azole resistance; lipopeptides.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Time–kill curves of two A. fumigatus isolates. A. fumigatus SSI-5586 treated with different concentrations of C14-NleRR-NH2 (A) and C14-WRR-NH2 (B). A. fumigatus SSI-4524 treated with different concentrations of C14-NleRR-NH2 (C) and C14-WRR-NH2 (D).
Figure 2
Figure 2
XTT assay of two isolates of A. fumigatus. A. fumigatus SSI-5586 treated with different concentrations of C14- NleRR-NH2 (A) and C14-WRR-NH2 (B). A. fumigatus SSI-4524 treated with different concentrations of C14- NleRR-NH2 (C) and C14-WRR-NH2 (D). *: p < 0.05 compared to control.
Figure 3
Figure 3
Optical microscopy of the A. fumigatus isolates after 24 h of treatment with C14-NleRR-NH2 at different concentrations. A. fumigatus SSI-4524 untreated (A), treated with 0.5X MIC (B), 1X MIC (C), and 2X MIC (D). A. fumigatus SSI-5586 untreated (E), treated with 0.5X MIC (F), 1X MIC (G), and 2X MIC (H).
Figure 4
Figure 4
Optical microscopy of the A. fumigatus isolates after 24 h of treatment with C14-WRR-NH2 at different concentrations. A. fumigatus SSI-4524 untreated (A), treated with 0.5X MIC (B), 1X MIC (C), and 2X MIC (D). A. fumigatus SSI-5586 untreated (E), treated with 0.5X MIC (F), 1X MIC (G), and 2X MIC (H).
See this image and copyright information in PMC

References

    1. Cadena J., Thompson G.R., Patterson T.F. Aspergillosis: Epidemiology, Diagnosis, and Treatment. Infect. Dis. Clin. N. Am. 2021;35:415–434. doi: 10.1016/j.idc.2021.03.008. - DOI - PubMed
    1. Jenks J.D., Nam H.H., Hoenigl M. Invasive aspergillosis in critically ill patients: Review of definitions and diagnostic approaches. Mycoses. 2021;64:1002–1014. doi: 10.1111/myc.13274. - DOI - PMC - PubMed
    1. Zakaria A., Osman M., Dabboussi F., Rafei R., Mallat H., Papon N., Bouchara J.P., Hamze M. Recent trends in the epidemiology, diagnosis, treatment, and mechanisms of resistance in clinical Aspergillus species: A general review with a special focus on the Middle Eastern and North African region. J. Infect. Public Health. 2020;13:1–10. doi: 10.1016/j.jiph.2019.08.007. - DOI - PubMed
    1. Russo A., Tiseo G., Menichetti F. Pulmonary Aspergillosis: An Evolving Challenge for Diagnosis and Treatment. Infect. Dis. Ther. 2020;9:511–524. doi: 10.1007/s40121-020-00315-4. - DOI - PMC - PubMed
    1. Latge J., Chamilos G. Aspergillus fumigatus and Aspergillosis in 2019. Clin. Microbiol. Rev. 2019;33:e00140-18. doi: 10.1128/CMR.00140-18. - DOI - PMC - PubMed