# The Four Critical Priority Fungi According to the World Health Organization and the Hope for New Therapies: A Focus on Cell Wall Antifungal Targets

**Authors:** Gabriel Davi Marena, Gabriela Corrêa Carvalho, Martha Helena Chaves Magalhães, Julia Marcondes Figueiredo, Danilo Henrique Ramos, Joshua D. Nosanchuk, Carlos Pelleschi Taborda

PMC · DOI: 10.3390/jof12030162 · Journal of Fungi · 2026-02-25

## TL;DR

This paper reviews recent research on new antifungal treatments targeting the cell walls of four dangerous fungi identified by the WHO.

## Contribution

It compiles recent studies on cell wall-targeting therapies for the WHO's critical priority fungi.

## Key findings

- The WHO identified four fungi as critical global health threats due to high mortality and resistance.
- Cell wall-targeting therapies show promise for overcoming antifungal resistance.
- Recent research highlights new treatment approaches for these deadly fungal pathogens.

## Abstract

In 2022, the World Health Organization (WHO) released a list of four fungi identified as the most medically important global pathogens, resulting in Cryptococcus neoformans, Candidozyma auris (formerly Candida auris), Aspergillus fumigatus and Candida albicans being classified as the critical priority fungi. The purpose of this list is to encourage the prioritization of fungal research and public policies to strengthen its control and combat fungal diseases. Among the criteria used in the analysis by the WHO to determine these critical threat pathogens were numbers of deaths; annual incidence; current global distribution; trends in the last 10 years; hospitalization; complications and sequelae; preventability; access to diagnostic tests; evidence-based treatments; and antifungal resistance. Difficulties in treatment, including due to antifungal resistance, are a major factor in the morbidity and mortality of these fungi. The fungal cell wall plays a fundamental role in maintaining cellular architecture and contributing to fungal survival. Thus, new approaches targeting the cell wall have been and are being developed. This review article aims to bring together studies from the last ten years focusing on the development of new treatment alternatives targeting the cell walls of the four critical priority fungi and discussing their potential for combating these deadly fungi of worldwide clinical importance.

## Linked entities

- **Species:** Cryptococcus neoformans (taxon 5207), Candidozyma auris (taxon 498019), Aspergillus fumigatus (taxon 746128), Candida albicans (taxon 5476)

## Full-text entities

- **Genes:** Nrg1 (neuregulin 1) [NCBI Gene 211323] {aka 6030402G23Rik, ARIA, D230005F13Rik, GGF, GGFII, HRG}, Plb1 (phospholipase B1) [NCBI Gene 665270] {aka 4632413E21Rik, 4930433E17Rik, 4930539A06Rik}, Skap2 (src family associated phosphoprotein 2) [NCBI Gene 54353] {aka 2610021A10Rik, RA70, SKAP-HOM, Saps, Scap2, mSKAP55R}, Cndp2 (CNDP dipeptidase 2) [NCBI Gene 66054] {aka 0610010E05Rik, Cn2, Dip-2, Pep-1, Pep1}, Spt (salivary protein cluster) [NCBI Gene 111363], Pigw (phosphatidylinositol glycan anchor biosynthesis, class W) [NCBI Gene 70325] {aka 2610044A17Rik, Gwt1, PIG-W}, Sh2d1a (SH2 domain containing 1A) [NCBI Gene 20400] {aka Gm686, SAP}, Pcdh15 (protocadherin 15) [NCBI Gene 11994] {aka Gm9815, Ush1f, av, nmf19, roda}, C1s1 (complement component 1, s subcomponent 1) [NCBI Gene 50908] {aka C1s, C1sa}, Tspyl2 (TSPY-like 2) [NCBI Gene 52808] {aka CDA1, CINAP, DENTT, DXBwg1396e, DXHXS1008E, E130307F10Rik}, Ece1 (endothelin converting enzyme 1) [NCBI Gene 230857] {aka ECE-1, ECE-1a, ECE-1b, ECE-1c1, ECE-1d}
- **Diseases:** RVVC (MESH:D002181), rheumatic disease (MESH:D012216), Fungal (MESH:D009181), Malaria (MESH:D008288), cystic fibrosis (MESH:D003550), meningitis (MESH:D008580), bacterial diseases (MESH:D001424), deaths (MESH:D003643), meningoencephalitis (MESH:D008590), coccidioidomycosis (MESH:D003047), viral infections (MESH:D014777), opportunistic infections (MESH:D009894), injury to (MESH:D014947), infected (MESH:D007239), invasive aspergillosis (MESH:D055744), C. auris candidemia (MESH:C000656864), AIDS (MESH:D000163), COVID-19 (MESH:D000086382), liver cirrhosis (MESH:D008103), lung disease (MESH:D008171), parasite infections (MESH:D010272), allergy (MESH:D004342), inflammation (MESH:D007249), cryptococcosis (MESH:D003453), hematologic malignancy (MESH:D019337), cytotoxicity (MESH:D064420), pulmonary aspergillosis (MESH:D055732), infectious disease (MESH:D003141), candidemia (MESH:D058387), asthma (MESH:D001249), neutropenic (MESH:D044504), hypertension (MESH:D006973), aspergillosis (MESH:D001228), neutropenia (MESH:D009503), Cryptococcal diseases (MESH:D016919)
- **Chemicals:** isavuconazole (MESH:C508735), Chitin (MESH:D002686), polystyrene (MESH:D011137), salt (MESH:D012492), sphingolipid (MESH:D013107), fatty acids (MESH:D005227), peptides (MESH:D010455), oil (MESH:D009821), geraniol (MESH:C007836), methanol (MESH:D000432), carbon (MESH:D002244), cyclopentanone (MESH:C007201), molecular oxygen (MESH:D010100), beta(1,6)-glucan (MESH:C064197), ASP9726 (MESH:C000592174), alpha-Cyperone (MESH:C583938), GalGXM (MESH:C432127), Isoeugenol (MESH:C036643), hydrogen peroxide (MESH:D006861), echinocandin (MESH:D054714), ethanol (MESH:D000431), ribose (MESH:D012266), crystal violet (MESH:D005840), terpenes (MESH:D013729), beta(1,3)-glucan (MESH:C033363), Ibrexafungerp (MESH:C569338), 5,11-Dimethyl-5H-indolo[2,3-b]quinoline (MESH:C055575), Auranofin (MESH:D001310), Triclosan (MESH:D014260), catecholamine (MESH:D002395), Myriocin (MESH:C001996), Enfumafungin (MESH:C421868), amino acids (MESH:D000596), chloroform (MESH:D002725), superoxide anions (MESH:D013481), Ergosterol (MESH:D004875), Anidulafungin (MESH:D000077612), manganese (MESH:D008345), Oteseconazole (MESH:C000599187), linalool (MESH:C018584), glucan (MESH:D005936), calcium (MESH:D002118), Calcofluor White (MESH:C007061), CHQS (MESH:C004357), F901318 (MESH:C000626907), JAT (MESH:C055785), pyrimidine (MESH:C030986), pentoses (MESH:D010429), SHAM (MESH:C005703), Fleagrass (-), methicillin (MESH:D008712), nickel (MESH:D009532), NEM (MESH:C058866), cholesterol (MESH:D002784), aldehyde (MESH:D000447), xylose (MESH:D014994), ROS (MESH:D017382), Rezafungin (MESH:C000629634), PAL (MESH:C005413), phosphatidylcholine (MESH:D010713)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Cryptococcus deneoformans (Cryptococcus neoformans serotype D, species) [taxon 40410], Human immunodeficiency virus 1 (no rank) [taxon 11676], Candidozyma auris (species) [taxon 498019], Scedosporium apiospermum (species) [taxon 563466], Aspergillus sp. (species) [taxon 5065], Pichia kudriavzevii (species) [taxon 4909], Hormonema carpetanum (species) [taxon 284138], Candidozyma haemuli (species) [taxon 45357], Cannabis sativa (species) [taxon 3483], Lomentospora prolificans (species) [taxon 41688], Mus musculus (house mouse, species) [taxon 10090], Micromonospora (genus) [taxon 1873], Fusarium oxysporum (species) [taxon 5507], Candida albicans (species) [taxon 5476], Enterococcus faecalis (species) [taxon 1351], Cryptococcus neoformans (Cryptococcus neoformans serotype A, species) [taxon 5207], Cryptococcus sp. (in: basidiomycete fungi) (species) [taxon 2046349], Cinnamomum verum (Ceylon cinnamon, species) [taxon 128608], Fungi (kingdom) [taxon 4751], Cryptolepis sanguinolenta (species) [taxon 1882729], Nakaseomyces glabratus (species) [taxon 5478], Cavia porcellus (domestic guinea pig, species) [taxon 10141], C. elegans [taxon 328850], Homo sapiens (human, species) [taxon 9606], Aspergillus fumigatus (species) [taxon 746128], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Galleria mellonella (greater wax moth, species) [taxon 7137], Malus domestica (apple, species) [taxon 3750]
- **Mutations:** S678P

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC13028124/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13028124/full.md

## References

166 references — full list in the complete paper: https://tomesphere.com/paper/PMC13028124/full.md

---
Source: https://tomesphere.com/paper/PMC13028124