Antifungal resistance: what if chance outperforms natural selection?

Excellent articulation between the in silico, in vitro and in vivo phases, with clear and quantified GO/NO-GO/PIVOT criteria that permit objective decision-making at each stage, thereby limiting the researcher's confirmation biases.

The hypothesis proposes an original and theoretically coherent mechanism that transfers the concept of 'budding speciation' (speciation by founder effect) from the phylogeography of macro-eukaryotes to the evolution of antifungal resistance in fungal pathogens. This conceptual bridge is novel and well-argued.

The hypothesis is judged to be original, proposing a non-standard mechanism (drift plus parasexual introgression) to account for the emergence of resistance, which could fill a gap in purely selective models.

The item addresses an unmet clinical need: the stochastic emergence of antifungal resistance within biofilms (Candida auris, C. albicans) is poorly understood, yet critical for hospital settings. The immediate market is the molecular diagnosis of emerging resistance (early detection tests for rare alleles) for diagnostic companies such as bioMérieux, Roche Molecular Diagnostics, or Cepheid, which market antifungal resistance panels (market estimated at €1.2 billion in 2028).

High conceptual originality: the hypothesis of stochastic fixation via budding speciation in fungal biofilms represents a departure from the dominant paradigm of adaptive selection, offering a novel mechanistic angle to explain the emergence of antifungal resistance, which is highly attractive for exploratory programmes (ERC, ANR JCJC).