The Yin and Yang of Current Antifungal Therapeutic Strategies: How Can We Harness Our Natural Defenses?

Overview

Journal Front Pharmacol

Date 2019 Feb 27

PMID 30804788

Citations 18

Authors

Tomas Di Mambro

Ilaria Guerriero

Luigi Aurisicchio

Mauro Magnani

Emanuele Marra

Affiliations

Soon will be listed here.

Abstract

Fungal infections have aroused much interest over the last years because of their involvement in several human diseases. Immunocompromission due to transplant-related therapies and malignant cancer treatments are risk factors for invasive fungal infections, but also aggressive surgery, broad-spectrum antibiotics and prosthetic devices are frequently associated with infectious diseases. Current therapy is based on the administration of antifungal drugs, but the occurrence of resistant strains to the most common molecules has become a serious health-care problem. New antifungal agents are urgently needed and it is essential to identify fungal molecular targets that could offer alternatives for development of treatments. The fungal cell wall and plasma membrane are the most important structures that offer putative new targets which can be modulated in order to fight microbial infections. The development of monoclonal antibodies against new targets is a valid therapeutic strategy, both to solve resistance problems and to support the immune response, especially in immunocompromised hosts. In this review, we summarize currently used antifungal agents and propose novel therapeutic approaches, including new fungal molecular targets to be considered for drug development.

Citing Articles

Antifungals: From Pharmacokinetics to Clinical Practice.

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PMID: 37237787 PMC: 10215229. DOI: 10.3390/antibiotics12050884.

Antibodies to Combat Fungal Infections: Development Strategies and Progress.

Rabaan A, Alfaraj A, Alshengeti A, Alawfi A, Alwarthan S, Alhajri M Microorganisms. 2023; 11(3).

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Sources of Antifungal Drugs.

Vanreppelen G, Wuyts J, Van Dijck P, Vandecruys P J Fungi (Basel). 2023; 9(2).

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Repurposing Antifungals for Host-Directed Antiviral Therapy?.

Schloer S, Goretzko J, Rescher U Pharmaceuticals (Basel). 2022; 15(2).

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Therapeutic Effect of an Antibody-Derived Peptide in a Model of Systemic Candidiasis.

Ottaviano E, Borghi E, Giovati L, Falleni M, Tosi D, Magliani W Int J Mol Sci. 2021; 22(20).

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References

Ghannoum M, Rice L . Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev. 1999; 12(4):501-17. PMC: 88922. DOI: 10.1128/CMR.12.4.501. View

San Millan R, Elguezabal N, Regulez P, Moragues M, Quindos G, Ponton J . Effect of salivary secretory IgA on the adhesion of Candida albicans to polystyrene. Microbiology (Reading). 2000; 146 ( Pt 9):2105-2112. DOI: 10.1099/00221287-146-9-2105. View

Ho M, Bolgiano B, Corbel M . Assessment of the stability and immunogenicity of meningococcal oligosaccharide C-CRM197 conjugate vaccines. Vaccine. 2000; 19(7-8):716-25. DOI: 10.1016/s0264-410x(00)00261-9. View

Douglas C . Fungal beta(1,3)-D-glucan synthesis. Med Mycol. 2002; 39 Suppl 1:55-66. DOI: 10.1080/mmy.39.1.55.66. View

Marr K, Carter R, Crippa F, Wald A, Corey L . Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002; 34(7):909-17. DOI: 10.1086/339202. View

Kontoyiannis D, Lewis R . Antifungal drug resistance of pathogenic fungi. Lancet. 2002; 359(9312):1135-44. DOI: 10.1016/S0140-6736(02)08162-X. View

Delmas G, Park S, Chen Z, Tan F, Kashiwazaki R, Zarif L . Efficacy of orally delivered cochleates containing amphotericin B in a murine model of aspergillosis. Antimicrob Agents Chemother. 2002; 46(8):2704-7. PMC: 127382. DOI: 10.1128/AAC.46.8.2704-2707.2002. View

Roncero C . The genetic complexity of chitin synthesis in fungi. Curr Genet. 2002; 41(6):367-78. DOI: 10.1007/s00294-002-0318-7. View

Garbino J, Kolarova L, Rohner P, Lew D, Pichna P, Pittet D . Secular trends of candidemia over 12 years in adult patients at a tertiary care hospital. Medicine (Baltimore). 2002; 81(6):425-33. DOI: 10.1097/00005792-200211000-00003. View

10.

Matthews R, Rigg G, Hodgetts S, Carter T, Chapman C, Gregory C . Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. Antimicrob Agents Chemother. 2003; 47(7):2208-16. PMC: 161838. DOI: 10.1128/AAC.47.7.2208-2216.2003. View

11.

Husain S, Alexander B, Munoz P, Avery R, Houston S, Pruett T . Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Clin Infect Dis. 2003; 37(2):221-9. DOI: 10.1086/375822. View

12.

Dadachova E, Nakouzi A, Bryan R, Casadevall A . Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection. Proc Natl Acad Sci U S A. 2003; 100(19):10942-7. PMC: 196907. DOI: 10.1073/pnas.1731272100. View

13.

Moragues M, Omaetxebarria M, Elguezabal N, Sevilla M, Conti S, Polonelli L . A monoclonal antibody directed against a Candida albicans cell wall mannoprotein exerts three anti-C. albicans activities. Infect Immun. 2003; 71(9):5273-9. PMC: 187351. DOI: 10.1128/IAI.71.9.5273-5279.2003. View

14.

Hobson R . The global epidemiology of invasive Candida infections--is the tide turning?. J Hosp Infect. 2003; 55(3):159-68. DOI: 10.1016/j.jhin.2003.08.012. View

15.

Eggimann P, Garbino J, Pittet D . Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis. 2003; 3(11):685-702. DOI: 10.1016/s1473-3099(03)00801-6. View

16.

Masuoka J . Surface glycans of Candida albicans and other pathogenic fungi: physiological roles, clinical uses, and experimental challenges. Clin Microbiol Rev. 2004; 17(2):281-310. PMC: 387410. DOI: 10.1128/CMR.17.2.281-310.2004. View

17.

Dadachova E, Burns T, Bryan R, Apostolidis C, Brechbiel M, Nosanchuk J . Feasibility of radioimmunotherapy of experimental pneumococcal infection. Antimicrob Agents Chemother. 2004; 48(5):1624-9. PMC: 400592. DOI: 10.1128/AAC.48.5.1624-1629.2004. View

18.

Larsen R, Pappas P, Perfect J, Aberg J, Casadevall A, Cloud G . Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother. 2005; 49(3):952-8. PMC: 549259. DOI: 10.1128/AAC.49.3.952-958.2005. View

19.

Richardson M . Changing patterns and trends in systemic fungal infections. J Antimicrob Chemother. 2005; 56 Suppl 1:i5-i11. DOI: 10.1093/jac/dki218. View

20.

Torosantucci A, Bromuro C, Chiani P, De Bernardis F, Berti F, Galli C . A novel glyco-conjugate vaccine against fungal pathogens. J Exp Med. 2005; 202(5):597-606. PMC: 2212864. DOI: 10.1084/jem.20050749. View