Retinoids in Fungal Infections: From Bench to Bedside
Abstract
:1. Introduction
2. Methods and Study Design
2.1. Search Strategy
2.2. Inclusion Criteria
2.3. Exclusion Criteria
3. Results
3.1. Effectiveness of Retinoids against Opportunistic Fungi That Colonize the Skin and Mucosae in Humans
3.1.1. Candida
3.1.2. Rhodotorula Mucilaginosa
3.1.3. Malassezia
3.2. Effectiveness of Retinoids against Environmental Human Pathogenic Filamentous Fungi
3.2.1. Aspergillus spp.
3.2.2. Fonsecaea spp.
3.2.3. Dermatophytes
3.3. Efficacy of Retinoids against Pneumocystis
Pneumocystis
Fungi | Spp. | Clinical/Experimental Model | Pathological Model | Retinoid | Combination | Results | Reference |
---|---|---|---|---|---|---|---|
Candida | albicans | In vitro culture | Retinoid derivatives containing a benzimidazole moiety | Antimicrobial activity MIC 1.56μg/mL | [16] | ||
albicans | In vitro culture | 1 g of Tazarotene 0.1% gel dissolved in 3mL of physiological solution | Fungistatic activity | [12] | |||
glabrata | In vitro culture | 1 g of Tazarotene 0.1% gel dissolved in 3mL of physiological solution | Fungistatic activity | [12] | |||
krusei | In vitro culture | Retinoid derivatives containing a benzimidazole moiety | Antimicrobial activity MIC 1.56μg/mL | [16] | |||
Not specified | Human | Chronic hyperplastic candidiasis nystatin-resistant | 0.18% isotretinoin applied twice a day for one month | Clinical resolution after one month | [17] | ||
Malassezia | furfur | Human | Pityriasis versicolor | Retinoic acid 0.05% cream vs. retinoic acid 0.05% lotion twice daily for 3 weeks | 50 patients totally. 33 patients (73.33%) and 3 weeks in 45 patients (97.83%) with a mean of 2.27 weeks | [25] | |
Not specified | Human | Pityriasis versicolor | Adapalene gel vs. ketoconazole 2% | Clinical resolution after 4 weeks and 30/40 (75%) presented mycological negative test vs. Ketoconazole cream 2% 28/40 (70%) and 28/40 (70%) | [26] | ||
Not specified | Human | Pityriasis versicolor | Oral isotretinoin 20 mg/day (0,4 mg/kg/day) for 6 weeks | Clinical resolution after 6 weeks | [28] | ||
Aspergillus | fumigatus | structural bioinformatic analysis | ATRA | Competitive inhbitor of the Hsp90 ATP-binding site | [13] | ||
fumigatus | In vitro colture | ATRA | Fungistatic activity (0.5 and 1 mM) down-regulation of HSP90 mRNa and protein expression; enhances the phagocytosis of macrophages (5 or 10mM) | [13] | |||
fumigatus | Rat | Invasive pulmonary aspergillosis (IPA) | ATRA, 2 mg/kg i.p. for 6 days | Alone; versus posaconazole; versus vehicol | Reduction in mortality of IPA | [13] | |
niger | Human | Onychomycosis | Tazarotene 0.1% gel twice daily for three months | Alone or plus tioconazole (28% nail paint) | Clinical resolution of OM after three months | [32] | |
flavus | Human | Onychomycosis | Tazarotene 0.1% gel twice daily for three months | Alone or plus tioconazole (28% nail paint) | Clinical resolution of OM after three months | [32] | |
fumigatus | Murine model | Keratitis | Fenretinide 100 μM subconjunctival injection | Inhibition of neutrophil recruitment and IL-1β production | [34] | ||
Dermatophyte (Trichophyton) | rubrum | Human | Onychomycosis | Tazarotene 0.1% gel once daily for 12 weeks | Clinical resolution | [12] | |
mentagrophytes | Human | Onychomycosis | Tazarotene 0.1% gel once daily for 12 weeks | Clinical resolution | [12] | ||
verrucosum | In vitro culture | 1 g of Tazarotene 0.1% gel dissolved in 3 mL of physiological solution | Fungistatic activity | [12] | |||
tonsurans | In vitro culture | 1 g of Tazarotene 0.1% gel dissolved in 3 mL of physiological solution | Fungistatic activity | [12] | |||
Dermatophyte (Epidermophyton) | floccosum | Human | Onychomycosis | Tazarotene 0.1% gel once daily for 12 weeks | Fungistatic activity | [12] | |
Pneumocystis | jiroveci | Mice and rats | pneumonia | ATRA 5 mg/kg/day in 8% DMSO | Primaquine 2 mg/kg/day in water | Engaged myeloid-derived suppressor cells | [48] |
Fonsecaea | Not specified | Human | Chromoblastomycosis | Acitretin 50 mg/day | Itraconazole and 200 mg/day topical imiquimod for 5 weeks | Clinical resolution | [37] |
Not specified | Human | Chromoblastomycosis | Acitretin 20 mg/day for 5 weeks | Itraconazole and 200 mg/day topical imiquimod for 5 weeks | Clinical resolution | [37] | |
monophora | Human | Chromoblastomycosis | Acitretin 20 mg/Kg for 1 month | Itraconazole 200 mg/day for 1 month | Clinical resolution | [38] | |
Rhodotorula | mucilaginosa | Human | Onychomycosis and psoriasis | Oral acitretin 10 mg/day for 8 weeks | Topical calcipotriol/betamethasone for 8 weeks | Clinical improvement within 8 weeks | [21] |
4. Discussion
Unmet Needs in Fungal Infections
5. Conclusions and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ABPA | Allergic Bronchial Pulmonary Aspergillosis |
AIDS | Acquired Immunodeficiency Syndrome |
AML | Acute Myeloid Leukaemia |
APL | Acute Promyelocytic Leukaemia |
ATRA | All-Trans Retinoic Acid |
CPA | Chronic Pulmonary Aspergillosis |
DDSs | Drug Delivery Systems |
DMSO | Dimethyl sulfoxide |
EPSs | Extracellular Polymeric Substances |
IBA | Invasive Bronchial Aspergillosis |
IL-1β | Interleukin 1 beta |
IFN-γ | Interferon gamma |
IPA | Invasive Pulmonary Aspergillosis |
HIV | Human Immunodeficiency Virus |
HSP90 | Heat Shock Protein 90 |
JNK | c-Jun N-terminal Kinase |
LOX-1 | Lectin-type Oxidized LDL receptor 1 |
MDR | Multidrug resistance |
MDSCs | Myeloid-Derived Suppressor Cells |
MPO | Myeloperoxidase |
NEs | Nanoemulsions |
NLCs | Nanostructured Lipid Carriers |
OM | Onychomycosis |
OSI | Onychomycosis Severity Index |
PcP | Pneumocystis Pneumonia |
qRT-PCR | Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction |
QS | Quorum Sensing |
RARs | Retinoic Acid Receptors |
SAFS | Severe Asthma with Fungal Sensitization |
SLNs | Solid Lipid Nanoparticles |
SMX | sulfamethoxazole |
TMP | trimethoprim |
TPGS | D-α-tocopheryl-polyethylene-glycol-succinate |
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Tretinoin | Tazarotene | Isotretinoin | Acitretin | Fenretinide | Adapalene | |
---|---|---|---|---|---|---|
In vitro studiies | A. fumigatus | C. glabrata | A. fumigatus | |||
C. albicans | C. albicans | A. niger | ||||
Microsporum spp. | T. verrucosum | C. albicans | ||||
Trichophyton spp. | ||||||
Epidermophyton spp. | ||||||
In vivo studies | M. furfur | A. niger | M. furfur | F. monophora | A. fumigatus | M. furfur |
A. fumigatus | T. rubrum | P. jiroveci | R. mucilaginosa | |||
T. tonsurans | ||||||
T. mentagrophytes | ||||||
E. floccosum | ||||||
C. albicans | ||||||
A. flavus |
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Cosio, T.; Gaziano, R.; Zuccari, G.; Costanza, G.; Grelli, S.; Di Francesco, P.; Bianchi, L.; Campione, E. Retinoids in Fungal Infections: From Bench to Bedside. Pharmaceuticals 2021, 14, 962. https://doi.org/10.3390/ph14100962
Cosio T, Gaziano R, Zuccari G, Costanza G, Grelli S, Di Francesco P, Bianchi L, Campione E. Retinoids in Fungal Infections: From Bench to Bedside. Pharmaceuticals. 2021; 14(10):962. https://doi.org/10.3390/ph14100962
Chicago/Turabian StyleCosio, Terenzio, Roberta Gaziano, Guendalina Zuccari, Gaetana Costanza, Sandro Grelli, Paolo Di Francesco, Luca Bianchi, and Elena Campione. 2021. "Retinoids in Fungal Infections: From Bench to Bedside" Pharmaceuticals 14, no. 10: 962. https://doi.org/10.3390/ph14100962