In vitro interactions between primycin and different statins in their effects against some clinically important fungi
Abstract
The in vitro antifungal activities of primycin (PN) and various statins against some opportunistic pathogenic fungi were investigated. PN completely inhibited the growth of Candida albicans (MIC 64 μg ml−1) and Candida glabrata (MIC 32 μg ml−1), and was very effective against Paecilomyces variotii (MIC 2 μg ml−1), but had little effect on Aspergillus fumigatus, Aspergillus flavus or Rhizopus oryzae (MICs >64 μg ml−1). The fungi exhibited different degrees of sensitivity to the statins; fluvastatin (FLV) and simvastatin (SIM) exerted potent antifungal activities against a wide variety of clinically important fungal pathogens. Atorvastatin, rosuvastatin and lovastatin (LOV) had a slight effect against all fungal isolates tested, whereas pravastatin was completely ineffective. The in vitro interactions between PN and the different statins were investigated using a standard chequerboard titration method. When PN was combined with FLV, LOV or SIM, both synergistic and additive effects were observed. The extent of inhibition was higher when these compounds were applied together, and the concentrations of PN and the given statin needed to block fungal growth completely could be decreased by several dilution steps. Similar interactions were observed when the variability of the within-species sensitivities was investigated.
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The different fungi are not equally sensitive to statins in vitro; SIM exhibits the strongest antifungal activity against yeasts compared to filamentous fungi, whereas the reverse is true for FLV.
“The different fungi are not equally sensitive to statins in vitro, e.g.SIM exhibits the strongest antifungal activity against yeasts compared to filamentous fungi, whereas the reverse is true for FLV [18] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
The inhibition activity of statins on the growth of filamentous fungi was revealed in several zygomycetous and ascomycetous fungal species.
“The inhibition activity of statins on the growth of filamentous fungi was revealed in the cases of several zygo- [18,19,28,[31][32][33][34][35] and ascomycetous fungal species [18,25,28,29,36,37] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
Generally, synthetic statins are more effective than natural statins.
“Generally, the synthetic statins are more effective than the natural ones [18,19] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
The various statins exhibit different antifungal effects against yeasts; SIM displays the strongest activity, followed by FLV, ATO, ROS, and LOV, while PRA is completely ineffective.
“These studies demonstrated that the various statins exhibit different antifungal effects against yeasts.SIM displayed the strongest antifungal activity, followed by FLV, ATO, ROS, and LOV.PRA proved to be completely ineffective against them.”
From Statins as antifungal agents (2011) · cites this paper as [18]
Statins exhibit fungicidal or fungistatic effects against yeasts in a dose-dependent manner.
“Statins exhibit fungicidal or fungistatic effects against yeasts in a dose dependent-manner.”
From Statins as antifungal agents (2011) · cites this paper as [18]
Statins have effective antifungal potential against both yeast and filamentous fungi and can be combined with clinically used antifungal agents.
“Statins are interesting from this respect, as they have effective antifungal potential against both yeast and filamentous fungi; furthermore, they can be combined with clinically used antifungal agents.”
From Statins as antifungal agents (2011) · cites this paper as [18]
Natural statins (e.g. SIM and LOV) mainly exert antifungal activity in their active metabolite forms (hydrolysis of the lactone ring at pH 10) and are less effective as pro-drugs.
“The natural statins (e.g.SIM and LOV) mainly effect their antifungal activity in their active metabolite forms (hydrolysis of the lactone ring at pH 10), and they proved to be less effective as pro-drugs [18,19] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
Synergistic interaction was observed between primycin and FLV, LOV and SIM, and additive interaction between AMB and ATO or SIM in Paecilomyces variotii.
“Synergistic interaction was observed between PN and FLV, LOV and SIM, and an additive interaction was observed between AMB and ATO or SIM in the case of Paecilomyces variotii [18,28] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
Both synergistic and additive effects were observed on growth reduction of C. albicans and C. glabrata when primycin was combined with FLV, LOV, or SIM.
“Both synergistic and additive effects were observed on the growth reduction of C. albicans and C. glabrata when primycin (PN), a non-polyene macrolide lactone antibiotic complex, was combined with FLV, LOV, or SIM [18] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
Synergistic and additive interactions were revealed between statins and antifungal agents in zygomycetous fungal species.
“Synergistic and additive interactions were revealed between statins and antifungal agents in the case of zygomycetous fungal species [18,19,28,29,33] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
Remarkable antifungal effects were observed on growth of Rhizopus oryze when primycin was combined with statins in concentrations that could not inhibit fungal growth alone.
“Remarkable antifungal effects were observed on the growth of Rhizopus oryze when PN was combined with statins in concentrations that could not inhibit the fungal growth alone [18] .”
From Statins as antifungal agents (2011) · cites this paper as [18]
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- Authors
- Nyilasi, I., Kocsubé, S., Pesti, M., Lukács, G., Papp, T., & Vágvölgyi, C.
- Affiliations
- University of Szeged (HU)
- Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, H-6726 Szeged, Hungary
- University of Pecs (HU)
- Venue
- Journal of Medical Microbiology
- Publisher
- Microbiology Society
- Published
- 2010-02-01
- Volume
- 59
- Issue
- 2
- Pages
- 200-205
- ISSN
- 0022-2615 (ISSN-L)
- 1473-5644
- OpenAlex
- W2127976221
- Cited by
- 35
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 6 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 4 · 2015: 3 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medical Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- statins, antifungal drug interactions, Candida albicans, Candida glabrata, Paecilomyces variotii, Aspergillus fumigatus, Aspergillus flavus, Rhizopus oryzae, fluvastatin, simvastatin, lovastatin, atorvastatin, rosuvastatin, pravastatin, drug synergy, antifungal susceptibility, opportunistic fungal pathogens
- MeSH terms
- Antifungal Agents, Drug Interactions, Fungi, Microbial Sensitivity Tests, Macrolides, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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