# Experimental Evolution of Pathogenic Candida spp.: Insights into Adaptive Processes and Evolutionary Dynamics

**Authors:** Gonçalo Sousa, Inês Correia, Ana Rita Bezerra

PMC · DOI: 10.3390/microorganisms14020273 · Microorganisms · 2026-01-24

## TL;DR

This review explores how pathogenic Candida species adapt and develop antifungal resistance through experimental evolution, highlighting genome plasticity as a key driver.

## Contribution

The paper provides a comprehensive review of experimental evolution in Candida spp., emphasizing genome plasticity and antifungal resistance dynamics.

## Key findings

- Genome plasticity, including aneuploidy and copy number variation, is central to Candida's rapid adaptation.
- Azole resistance has been widely studied, but echinocandin and polyene resistance remain underexplored.
- Current research lacks broad species coverage and combined therapy evaluations.

## Abstract

Among Candida species, several are major opportunistic fungal pathogens capable of causing a wide spectrum of infections, ranging from superficial mucosal conditions to severe systemic diseases. Their success as human pathogens is largely due to their ability to rapidly adapt to diverse host environments and develop resistance to antifungal agents. Experimental evolution provides a powerful framework for understanding these adaptive processes by observing evolutionary change in real-time. Although most studies rely on in vitro systems and a limited set of Candida species, there is strong evidence that genome plasticity, including aneuploidy, loss of heterozygosity, and copy number variation, plays a central role in driving rapid adaptation. Experimental evolution has also been applied to study the dynamics of antifungal resistance, particularly to azoles, although relatively fewer studies have explored resistance to echinocandins and polyenes. This review summarizes current knowledge on experimental evolution in pathogenic Candida species, with a focus on genome plasticity, adaptation to host-imposed stress, and particularly on the emergence of antifungal resistance. It also identifies critical research gaps, including the need for broader species coverage, investigation of underexplored antifungal classes, and evaluation of combined therapies. A deeper understanding of these dynamics is essential to improve antifungal strategies and counter the growing threat of drug-resistant Candida spp. infections.

## Linked entities

- **Chemicals:** azoles (PubChem CID 699591)

## Full-text entities

- **Diseases:** C. parapsilosis (OMIM:211750), term infection (MESH:D000088562), C. albicans infection (MESH:D007239), candidiasis (MESH:D002177), oral candidiasis (MESH:D002180), invasive (MESH:D009361), bloodstream (MESH:D018805), aneuploidies (MESH:D000782), Fungal infections (MESH:D009181), injury to (MESH:D014947), oropharyngeal candidiasis (MESH:D009959), candidemia (MESH:D058387), EE (MESH:D009374), AIDS (MESH:D000163)
- **Chemicals:** 14-methyl-3,6-diol (-), H2O2 (MESH:D006861), glucose uridine diphosphate (MESH:D014532), NADPH (MESH:D009249), ergosterol (MESH:D004875), Amphotericin B (MESH:D000666), sterol (MESH:D013261), itraconazole (MESH:D017964), lipopeptides (MESH:D055666), Polyenes (MESH:D011090), Fluconazole (MESH:D015725), ROS (MESH:D017382), caspofungin (MESH:D000077336), phosphorus (MESH:D010758), AMPs (MESH:D000089882), Allylamines (MESH:D000499), ketoconazole (MESH:D007654), Azole (MESH:D001393), nitrogen (MESH:D009584), clotrimazole (MESH:D003022), posaconazole (MESH:C101425), lanosterol (MESH:D007810), voriconazole (MESH:D065819), geldanamycin (MESH:C001277), Echinocandin (MESH:D054714)
- **Species:** Lodderomyces parapsilosis (species) [taxon 5480], Candida [taxon 1535326], Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Drosophila melanogaster (fruit fly, species) [taxon 7227], Aspergillus (genus) [taxon 5052], Pichia kudriavzevii (species) [taxon 4909], Candida albicans (species) [taxon 5476], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Candidozyma auris (species) [taxon 498019], Caenorhabditis elegans (species) [taxon 6239], Mus musculus (house mouse, species) [taxon 10090], Nakaseomyces glabratus (species) [taxon 5478], Pneumocystis jirovecii (species) [taxon 42068], Cryptococcus neoformans (Cryptococcus neoformans serotype A, species) [taxon 5207], Candida albicans SC5314 (strain) [taxon 237561], Fungi (kingdom) [taxon 4751], Human immunodeficiency virus 1 (no rank) [taxon 11676]
- **Mutations:** W1370R, C463T, W715L, DeltaF659, E1083Q, D666E, Y372C, L280F, D66N, serine to leucine, G271T, Y132F, F126L, T896I, R1422L, T588A, W681L, A272V, L703F, F214S, P822L, N977D, Y5H, DeltaF658, A511G, K171E, 5L, P683S, P155S, L664R, V742A, F506K, Q350L, N556K, Y132H, G450E, L207I, C444Y, A1161V, R467K, S405F, F449S, A736V, T229A, S663P, D446N, D116E, A506V, H409Y, R376W, S656P, K143R, D66H, R495G, T1987C, A651T, P683H, G997V, Y584C, F708S
- **Cell lines:** SC5314 — Homo sapiens (Human), Embryonic stem cell (CVCL_6F20), ATCC-10231 — Homo sapiens (Human), Hereditary hemorrhagic telangiectasia, Transformed cell line (CVCL_W904)

## Full text

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## Figures

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## References

107 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942677/full.md

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Source: https://tomesphere.com/paper/PMC12942677