Advances in the Treatment of Invasive Fungal Disease

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2023 May 4

PMID 37141208

Authors

Zhuan Zhang

Gerald F Bills

Zhiqiang An

Affiliations

Soon will be listed here.

Abstract

With over 300 million severe cases and 1.5 million deaths annually, invasive fungal diseases (IFDs) are a major medical burden and source of global morbidity and mortality. The World Health Organization (WHO) recently released the first-ever fungal priority pathogens list including 19 fungal pathogens, considering the perceived public health importance. Most of the pathogenic fungi are opportunistic and cause diseases in patients under immunocompromised conditions such as HIV infection, cancer, chemotherapy, transplantation, and immune suppressive drug therapy. Worryingly, the morbidity and mortality caused by IFDs are continuously on the rise due to the limited available antifungal therapies, the emergence of drug resistance, and the increase of population that is vulnerable to IFDs. Moreover, the COVID-19 pandemic worsened IFDs as a globe health threat as it predisposes the patients to secondary life-threatening fungi. In this mini-review, we provide a perspective on the advances and strategies for combating IFDs with antifungal therapies.

Citing Articles

Occurrence of Pathogenic and Allergenic Molds in the Outdoor and Indoor Environment of a Major Hospital and Molecular Epidemiology of in Kuwait.

Asadzadeh M, Ahmad S, Hagen F, Meis J, Khan Z J Fungi (Basel). 2025; 11(2).

PMID: 39997377 PMC: 11856096. DOI: 10.3390/jof11020083.

Computational and In silico study of novel fungicides against combating root rot, gray mold, fusarium wilt, and cereal rust.

Naimuzzaman M, Hasan M, Kumer A, Hossin A, Harun-Ur-Rashid M, Roy S PLoS One. 2025; 20(1):e0316606.

PMID: 39888972 PMC: 11785347. DOI: 10.1371/journal.pone.0316606.

The Significance of Mono- and Dual-Effective Agents in the Development of New Antifungal Strategies.

Zobi C, Algul O Chem Biol Drug Des. 2025; 105(1):e70045.

PMID: 39841631 PMC: 11753615. DOI: 10.1111/cbdd.70045.

Patterns of Amphotericin B Use and Factors Related to Mortality in a Low-Middle Income Country: An Observational and Longitudinal Study.

Valladales-Restrepo L, Soto-Romero L, Navarrete-Santa L, Montoya-Garcia R, Rios-Montoya J, Sabogal-Ortiz A Antibiotics (Basel). 2024; 13(11).

PMID: 39596710 PMC: 11591292. DOI: 10.3390/antibiotics13111015.

Antifungal and anti-biofilm effects of hydrazone derivatives on spp.

Popczyk P, Ghinet A, Bortolus C, Kamus L, Lensink M, de Ruyck J J Enzyme Inhib Med Chem. 2024; 39(1):2429109.

PMID: 39589067 PMC: 11600518. DOI: 10.1080/14756366.2024.2429109.

References

Zhao M, Zhang F, Zarnowski R, Barns K, Jones R, Fossen J . Turbinmicin inhibits Candida biofilm growth by disrupting fungal vesicle-mediated trafficking. J Clin Invest. 2020; 131(5). PMC: 7919718. DOI: 10.1172/JCI145123. View

Cruz M, Cristy S, Guha S, Buda De Cesare G, Evdokimova E, Sanchez H . Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections. Nat Commun. 2022; 13(1):6047. PMC: 9562342. DOI: 10.1038/s41467-022-33613-1. View

Trevino-Rangel R, Gonzalez G, Montoya A, Rojas O, Elizondo-Zertuche M, Alvarez-Villalobos N . Recent Antifungal Pipeline Developments against : A Systematic Review. J Fungi (Basel). 2022; 8(11). PMC: 9695453. DOI: 10.3390/jof8111144. View

Edwards Jr J, Schwartz M, Schmidt C, Sobel J, Nyirjesy P, Schodel F . A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis. 2018; 66(12):1928-1936. PMC: 5982716. DOI: 10.1093/cid/ciy185. View

Rodrigues M, Nosanchuk J . Fungal diseases as neglected pathogens: A wake-up call to public health officials. PLoS Negl Trop Dis. 2020; 14(2):e0007964. PMC: 7032689. DOI: 10.1371/journal.pntd.0007964. View

Liu W, Yuan L, Wang S . Recent Progress in the Discovery of Antifungal Agents Targeting the Cell Wall. J Med Chem. 2020; 63(21):12429-12459. DOI: 10.1021/acs.jmedchem.0c00748. View

Fisher M, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell E, Bowyer P . Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol. 2022; 20(9):557-571. PMC: 8962932. DOI: 10.1038/s41579-022-00720-1. View

Datta K, Hamad M . Immunotherapy of Fungal Infections. Immunol Invest. 2015; 44(8):738-76. DOI: 10.3109/08820139.2015.1093913. View

Kumaresan P, da Silva T, Kontoyiannis D . Methods of Controlling Invasive Fungal Infections Using CD8 T Cells. Front Immunol. 2018; 8:1939. PMC: 5766637. DOI: 10.3389/fimmu.2017.01939. View

10.

Antoran A, Aparicio-Fernandez L, Pellon A, Buldain I, Martin-Souto L, Rementeria A . The monoclonal antibody Ca37, developed against Candida albicans alcohol dehydrogenase, inhibits the yeast in vitro and in vivo. Sci Rep. 2020; 10(1):9206. PMC: 7280234. DOI: 10.1038/s41598-020-65859-4. View

11.

McCarthy M . Pharmacokinetics and Pharmacodynamics of Ibrexafungerp. Drugs R D. 2021; 22(1):9-13. PMC: 8885872. DOI: 10.1007/s40268-021-00376-x. View

12.

Perfect J . The antifungal pipeline: a reality check. Nat Rev Drug Discov. 2017; 16(9):603-616. PMC: 5760994. DOI: 10.1038/nrd.2017.46. View

13.

Lionakis M, Drummond R, Hohl T . Immune responses to human fungal pathogens and therapeutic prospects. Nat Rev Immunol. 2023; 23(7):433-452. DOI: 10.1038/s41577-022-00826-w. View

14.

Hoenigl M, Sprute R, Egger M, Arastehfar A, Cornely O, Krause R . The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin. Drugs. 2021; 81(15):1703-1729. PMC: 8501344. DOI: 10.1007/s40265-021-01611-0. View

15.

Kumar A, Devan A, Nair B, Vinod B, Nath L . Harnessing the immune system against cancer: current immunotherapy approaches and therapeutic targets. Mol Biol Rep. 2021; 48(12):8075-8095. PMC: 8605995. DOI: 10.1007/s11033-021-06752-9. View

16.

Chen T, Batra J, Michalik D, Casillas J, Patel R, Ruiz M . Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases. Open Forum Infect Dis. 2022; 9(11):ofac535. PMC: 9645583. DOI: 10.1093/ofid/ofac535. View

17.

Hoenigl M, Seidel D, Sprute R, Cunha C, Oliverio M, Goldman G . COVID-19-associated fungal infections. Nat Microbiol. 2022; 7(8):1127-1140. PMC: 9362108. DOI: 10.1038/s41564-022-01172-2. View

18.

Aigner M, Lass-Florl C . Encochleated Amphotericin B: Is the Oral Availability of Amphotericin B Finally Reached?. J Fungi (Basel). 2020; 6(2). PMC: 7344640. DOI: 10.3390/jof6020066. View

19.

Bills G, Li Y, Chen L, Yue Q, Niu X, An Z . New insights into the echinocandins and other fungal non-ribosomal peptides and peptaibiotics. Nat Prod Rep. 2014; 31(10):1348-75. DOI: 10.1039/c4np00046c. View