Antifungal drug resistance is a growing global health concern, yet treatment options remain limited to just four classes: polyenes, azoles, allylamines, and echinocandins. Cryptococcus species are responsible for life-threatening meningoencephalitis and pulmonary infections, which cause over 140,000 deaths annually. The high mortality of Cryptococcus is driven by limited drug access, toxicity, persistence, and emerging resistance. To better understand antifungal resistance and identify novel therapeutics, we profiled a genetically diverse panel of Cryptococcus isolates spanning all major lineages (VNI, VNIII, VNIV, VGI-VGVI). Phenotypic assays were used to assess susceptibility to fluconazole (FLZ), 5-fluorocytosine (5-FC), and amphotericin B (AmpB), as well as the epigenetic inhibitors CPTH2 (a histone acetyltransferase inhibitor) and SAHA (a histone deacetylase inhibitor). We found lineage- and strain-specific variation in antifungal susceptibility, with disc-diffusion and microdilution assays yielding consistent patterns. Pharmacodynamic modelling revealed potent fungicidal activity of CPTH2 across all tested lineages. DNA content and chitin levels varied significantly by lineage and treatment: FLZ and CPTH2 induced DNA content increases in susceptible strains, suggesting a stress response, while 5-FC-induced chitin remodelling was most pronounced in resistant strains. Multivariate analysis identified chitin induction as a principal driver of phenotypic variance under antifungal stress. Our findings reveal lineage-specific antifungal responses in Cryptococcus, highlight the antifungal potential of epigenetic inhibitors such as CPTH2, and underscore the utility of phenotypic profiling to inform drug development and resistance surveillance.

We report a case of chronic granulomatous invasive aspergillosis in a 56-year-old male teacher from South Kordofan, Sudan, who underwent surgery in 2007 to remove his left orbital aspergillus granuloma. The patient developed progressive facial swelling beginning in 2017 and paraesthesia in the left zygomatico-maxillary region, despite initial treatment. A soft tissue mass in the left maxillary sinus and widespread bone loss affecting the zygomatic arch, maxillary antrum, and fronto-temporal lytic lesions were seen on computed tomography. Histopathological analysis confirmed the recurrence of aspergillosis. Itraconazole therapy was administered to the patient after surgical excision, although treatment compliance was subpar. A subsequent wide local excision was performed in 2021, but the patient developed post-operative complications, including wound infection and dysphagia, leading to death four days after surgery. This case highlights the aggressive nature of chronic invasive aspergillosis, the importance of adequate initial treatment duration, and the potential for devastating complications, including facial bone destruction and neurological involvement manifesting as paresthesia.

Emerging infectious diseases are one of the biggest challenges in a globalized world. To date, resources have been allocated to prevent and control the spread of zoonotic and livestock pathogens. We argue that, in line with the One Health approach, equitable efforts, financial resources, attention, and coordination are required for wildlife-only pathogens to halt biodiversity loss. Deploying the amphibian fungus Batrachochytrium salamandrivorans as a model, we demonstrate the unbalanced efforts among countries in Europe regarding surveillance, disease response, prevention, public outreach, and research. We compare investments with B. salamandrivorans l-free countries such as the United States, concluding that structural resources are urgently needed to curb the effects of this fungus within Europe and beyond. We encourage dialogue among authorities, researchers, and stakeholders and propose a coordinated European Union-level program of €6-10 million over 5-7 years to implement B. salamandrivorans action plans and define structural funding requirements for future wildlife disease mitigation.

BACKGROUND:Long-term exposure to indoor fungal bioaerosols is a recognised risk factor for respiratory illness, particularly in damp and poorly ventilated housing. However, the diversity and seasonal variability of these fungal communities are poorly understood. As part of the West London Healthy Home and Environment Study (WellHome), this study aimed to characterise the composition, diversity, and temporal dynamics of indoor fungal bioaerosols in urban UK homes, as compared with outdoor air, to inform future exposure baselines and policy development. METHODS:In this prospective, community-based observational study, 118 households were recruited across West London, UK, via community networks and partner organisations, prioritising families with children aged 5-17 years with asthma or allergies, from diverse socioeconomic backgrounds. Sampling occurred between Oct 3, 2022, and June 14, 2024. Participant data were collected via questionnaires completed by household members, capturing demographics, building characteristics, and respiratory health. Passive-air samplers were used in living rooms for 28 days during two seasonal campaigns, with concurrent outdoor sampling at four fixed community sites. Fungal bioaerosols were identified by ITS2 amplicon sequencing and quantified using broad-range quantitative PCR targeting the 18S rRNA gene. Diversity indexes and temporal dynamics were analysed using ecological statistics and generalised additive models. FINDINGS:118 households were enrolled, comprising 504 residents (263 women, 237 men, and four not reported). Among 504 participants who self-identified, the largest groups comprised individuals identifying as Black African (n=47), Somali (n=46), White British (n=42), and African (n=38), with additional representation from mixed race ethnic backgrounds (n=29), Black British (n=27), White (n=22), and Black Caribbean (n=18), alongside several other ethnicities each represented at lower frequencies. Of 118 households, 104 completed both seasonal campaigns and 14 completed one, yielding 262 air samples (222 indoor and 40 outdoor). DNA was successfully recovered from all samples, identifying 2027 fungal genera. Indoor environments showed significantly higher richness (mean 646 vs 495 amplicon sequence variants; p<0·0001) and Shannon diversity (4·21 vs 3·53; p<0·0001) than outdoors. Community composition differed markedly (permutational multivariate ANOVA p<0·0001), with Penicillium, Aspergillus, and Wallemia enriched indoors. Indoor fungal communities presented stronger seasonal cycling (R2=0·203) than outdoor communities (R2=0·012). Fungal burden across all homes had a median 11 043 genomic equivalence (GE); IQR 4598-20 579 GE. The highest levels were observed in homes with visible mould; one household showed elevated Aspergillus exposure linked to repeated asthma hospitalisations in a sensitised resident. INTERPRETATION:Indoor fungal bioaerosols are more diverse and dynamic than outdoor communities in urban UK homes. These findings establish foundational exposure data and highlight the need for incorporating fungal bioaerosol monitoring into public health policy to mitigate mould-related health risks. FUNDING:UK Research and Innovation (UKRI) Strategic Priorities Fund (SPF) Clean Air Programme.

Epizootic outbreaks of invasive pathogens, such as the fungal pathogen Batrachochytrium dendrobatidis (Bd), are increasingly recognized as a global threat to biodiversity. However, not all susceptible host populations are equally impacted by these disease outbreaks. While some populations persist despite intense infections and high mortality rates, others can transition to enzootic coexistence with the pathogen. Here, we use comparative peptidomics to identify differences in antimicrobial peptide (AMP) maturation in Bd-susceptible common midwife toads (Alytes obstetricans) through metamorphosis. Here, we show that animals that metamorphose before AMP immune maturation display a low-diversity AMP phenotype deficient in anti-Bd AMPs. Where a high incidence of postmetamorphic animals occur with immature AMPs, populations are associated with epizootic disease dynamics. Conversely, populations associated with mature AMPs are stable following invasion of the pathogen. Our results show that even intrinsically susceptible amphibian species can possess the tools that allow populations to recover following a severe Bd epizootic.

Aim The emergence of the fungal pathogen Batrachochytrium dendrobatidis (Bd) in South America has been attributed to multiple introductions and subsequent spread in a bidirectional latitudinal wave along the primary Andean cordilleras. This is supported for Ecuador by anecdotal evidence of declines in Bd-susceptible genera such as Telmatobius and Atelopus around the mid-1980s. We tested this hypothesis by combining published records of Bd with retrospective screenings of museum specimens (1950-2010) and surveys of contemporary populations to characterise the spatiotemporal and host-specific emergence of Bd in Ecuador. Location Ecuador. Methods We assembled a database of Bd records in Ecuadorian anurans (> 7000 samples) and assessed its spatiotemporal emergence using generalised linear mixed models and spatial clustering approaches. Data were also used to identify Bd prevalence within four representative genera of Ecuadorian anurans (Atelopus, Telmatobius, Gastrotheca and Pristimantis). We also used Bayesian approaches to test the probability of the presence of Bd in Ecuador prior to the first positive record. Results Our results overturn the prevailing narrative of Bd emergence in the Neotropics and provide a rare, long-term view of an invasive pathogen's trajectory from introduction to persistence. We found that: (1) Bd likely represents a novel pathogen to Ecuador; (2) Bd was first detected in 1974 and had become widespread by 1980; (3) there is no evidence supporting a bidirectional wave of spread; and (4) the genera Atelopus, Telmatobius and Gastrotheca experienced epizootic disease dynamics, with declines peaking in the 1990s. Main Conclusions We found that Bd is likely a novel pathogen that was introduced in the early 1970s and peaked in prevalence during the late 1980s and 1990s. The available evidence supports the conclusion that an outbreak of chytridiomycosis may have led to catastrophic declines in Ecuadorian amphibians. Disease dynamics have since subsided to enzootic coexistence in extant amphibian communities.

Abstract How fungal pathogens generate and maintain genetic diversity under sustained environmental drug pressure is central to understanding the emergence of antifungal resistance. In environmental moulds such as Aspergillus fumigatus , escalating exposure to agricultural fungicides that share targets with clinical azoles imposes chronic selection outside the host, yet the genomic mechanisms enabling long-term adaptation remains unclear. Here, we reconstruct the largest eukaryotic pangenome assembled to date, comprising over 1,000 A. fumigatus isolates collected across 34 countries spanning a century. Using network-based orthogroup clustering combined with ancestral state reconstruction, we show that the A. fumigatus pangenome is open and shaped by continual gene gain and loss. Pangenome-wide association analyses identify accessory genes associated with itraconazole resistance, indicating that resistance evolution occurs within broader genomic backgrounds and beyond canonical target-site mutations. We further reveal that the accessory genome is structured into distinct evolutionary cohorts, including lineage-restricted gene sets enriched for mobile genetic element– associated domains, notably Starship -linked genes. These patterns suggest that Starships contribute to clade-specific genome architecture while remaining largely constrained by phylogenetic boundaries. Time-calibrated phylogenetic modelling reveals a relatively slow rate of gene turnover—approximately two orthogroup events per century—demonstrating that large-scale genome evolution in A. fumigatus is decoupled from elevated point mutation rates and contrasts sharply with bacterial systems. Together, these findings establish a quantitative framework for fungal pangenome evolution and reveal how structured accessory genome dynamics underpin antifungal resistance and long-term adaptation in this major human pathogen. Significance Statement Antifungal resistance in Aspergillus fumigatus threatens global health, yet the genomic processes enabling long-term adaptation under environmental drug pressure remain poorly understood. Using a global, century-spanning pangenome, incorporating over 1,000 isolates, we quantify gene gain and loss dynamics in this major human pathogen. We show that the pangenome is open but evolves slowly, with only ∼2 gene turnover events per century. Accessory genes follow two distinct evolutionary modes: some are lineage-restricted, while others are broadly distributed and dynamically exchanged. Resistance is associated with lineage-specific accessory genes, highlighting a broader role of resistance formation than target-site mutations alone. These findings reveal how heterogeneous turnover dynamics shape adaptation to widespread antifungal exposure.

BACKGROUND:Trichophyton species cause the greatest burden of dermatophytosis worldwide, with the Trichophyton mentagrophytes species complex being particularly associated with the emergence of new aggressive infections. One emerging species, Trichophyton indotineae is notable for its clinical resistance to terbinafine antifungal treatment and rapid global spread. In this study we aim to characterise the epidemiology of this emerging pathogen using genomics. METHODS:In this retrospective genomic epidemiology study, to better understand the epidemiology of this disease, we sourced isolates collected from patients with severe cases of dermatophytosis (identified either by internal transcribed spacer sequencing or phenotypic characterisation) in the UK, Ireland, France, Canada, and India for the period 2014-23, including the T indotineae type strain from Japan. We used whole-genome sequencing to confirm 90 isolates were T indotineae, and antifungal susceptibility testing to assess susceptibility to terbinafine. FINDINGS:103 cases of severe dermatophytosis caused by Trichophyton species collected between 2018 and 2023 in the UK, France, Canada, Ireland, and India were included in this study. Susceptibility testing indicated that 63 (70%) of 90 T indotineae isolates were resistant to terbinafine (minimum inhibitory concentration [MIC] ≥0·5 mg/L). Pairwise genetic distances showed very high identity with only 147 (range 1-414) single-nucleotide polymorphisms (SNPs) separating isolates that were nested within a monophyletic phylogeny, supporting a single evolutionary origin of T indotineae. Genome-wide analyses identified multiple non-synonymous SNPs in SQLE (ERG1), the squalene epoxidase target of terbinafine, that were associated with terbinafine in vitro resistance of 0·5 mg/L or higher. However, six isolates exhibited high MIC values without SQLE mutations, suggesting the presence of alternative resistance mechanisms. INTERPRETATION:That no clear geographical clustering of isolates was observed confirms the rapid transcontinental spread of T indotineae from its likely centre of diversity in Asia. Our findings highlight the importance of better genomic surveillance to understand and manage this severe and rapidly emerging terbinafine-resistant dermatophyte. FUNDING:None.

BACKGROUND:Until 2020, azole resistance in Aspergillus fumigatus complex isolates in New Zealand was due to cyp51A hot spot mutations. This report details the appearance of environment-linked tandem repeat (TR)-related azole resistance genotypes since 2021. METHODS:Isolates were tested by broth micro-dilution. Clinical Laboratory Standards Institute criteria were used to define wild type (WT) and non-wild type (non-WT) isolates, which were identified by ß-tubulin gene sequencing and had their cyp51A genotype for azole resistance determined. Whole genome sequencing (WGS) was applied to two patient pairs of sequential WT and non-WT isolates. RESULTS:From January 2021 to June 2024, 15 of 147 (10.2%) A. fumigatus complex isolates were resistant or non-WT for one or more azole agents. Genotyping detected hot spot mutations in four and TR-associated resistance in nine. No mutations were detected in two isolates. Four of the five TR46 mutations were TR46/Y121F/T289A. Three of the four TR34 mutations were different. WGS of the paired isolates showed that the non-WT isolates were distinct. Azole-containing fungicides are available for home use from garden centres. Patients with TR-associated resistance did not have any obvious exposure to azole-containing fungicides. There was no evidence for healthcare-acquired transmission. CONCLUSIONS:A. fumigatus sensu stricto isolates with TR-mutations linked to environmental resistance are now present in New Zealand. Those at risk of invasive A. fumigatus infection should receive advice to avoid high-risk exposures. Reintroducing monitoring of azole-containing fungicides is recommended.

We are surrounded, in both indoor and outdoor environments, by air containing particles of biological origin (bioaerosols). We constantly inhale them, and, depending upon their size, they deposit in different parts of our airways. Despite their ubiquitous nature and our constant exposure, bioaerosol diversity and composition of the environment are not well characterized, and we understand little about which bioaerosols we are exposed to and how this impacts our health, either positively or negatively. Indoor/Outdoor Bioaerosols Interface and Relationships Network (BioAirNet), a Clean Air Programme-funded network, has recognized the need for the bioaerosol community to reflect on the current challenges facing bioaerosol exposure assessment and the determination of the associated cellular/molecular responses driving specific health outcomes. A series of online workshops for the bioaerosol community were hosted by BioAirNet in September 2022, which aimed to bring together global expertise to discuss the current challenges impeding improved assessment of bioaerosol exposure and understanding of the downstream cellular and molecular mechanisms driving health outcomes by discussing these challenges; considering where we need to be, where we are now and how we get there. Professional facilitation was key to their success, enabling the multidisciplinary bioaerosol community to explore and address these challenges within a focused and productive environment to prioritize themes and agree on action plans for continued momentum following the workshops. These themes were as follows: (1) conceptual model; (2) stakeholder mapping; (3) knowledge transfer; (4) writing project and (5) conference-type event, collectively covering research, knowledge mobilization and networking activities. A subsequent in-person follow-up workshop was held in November 2023. It provided an opportunity to share progress on the five themes, critique what had already been done and act as a launch-pad to progress the actions further. Delegates also had the opportunity to share ongoing or upcoming work, particularly projects requiring input from others, to encourage collaborative working and sharing expertise. The use of facilitated workshops is a valuable tool for all scientific communities to collectively explore and successfully address key issues within their field.

Ranaviruses infect cold-blooded vertebrates (amphibians, reptiles and fish), causing amphibian mass mortality events worldwide. Frog Virus 3 (FV3) and Common midwife toad virus (CMTV) have been responsible for amphibian declines in the United Kingdom and Spain, respectively. The Pyrenees National Park (PNP) is a protected area in France, where native amphibian species are being threatened by the introduction of non-native fish and the emerging fungal pathogen Batrachochytrium dendrobatidis (Bd). To our knowledge, information concerning ranavirus status within the PNP is scarce. Therefore, we analyzed samples from 239 archived specimens from three anuran species (Alytes obstetricans, Rana temporaria, and Bufo spinosus), collected from 2007 to 2017, for ranavirus presence using a qPCR assay. Results revealed ranavirus presence in three of the four sampled lakes, infecting two anuran species (A. obstetricans and R. temporaria). We provide evidence that an FV3-like virus has been present in amphibians from the PNP since at least 2009. Further efforts should be taken to understand the impacts of FV3 on amphibians inhabiting the Pyrenees.

The relationship between indoor air quality and public health remains under-researched. WellHome is a transdisciplinary community-based study that will engage with residents to co-design feasible and acceptable research to quantify air pollution exposure in 100 homes in West London and examine its potential to exacerbate asthma symptoms in children. Sampling strategies such as using air quality monitors and passive samplers placed in kitchens, children’s bedrooms, and living rooms, will be developed in collaboration with local ambassadors and participating households to measure multiple physical, chemical, microplastic, and biological contaminants. This will provide a comprehensive understanding of indoor air quality across the city’s socio-economic gradient. Other data collected will include housing types and tenure, ventilation practices, occupant behaviours, time-activity, and airway symptoms. Epidemiological analysis will examine air pollution exposure impacts on children’s respiratory health. The particulate mixture’s relative hazard will be evaluated in toxicity studies based on source profiles and activity patterns of participants, focusing on asthma exacerbation related pathways. The study’s findings will be communicated to participants through co-designed reports and inform evidence-based recommendations for reducing indoor air pollution in London and urban areas worldwide. By raising awareness and providing actionable insights, WellHome seeks to contribute to global efforts to improve the health and well-being of vulnerable communities.

Mountain lakes are rare ecological niches supporting unique species assemblages and are important sources of safe drinking water for wildlife, livestock and humans. Located at high altitude, these lakes are vulnerable to environmental stressors such as climate or land-use change, impacting their ecosystem functions. However, although trends in water temperature and physico-chemical composition have been fairly well studied in large mountain lakes, the same cannot be said for small- to medium-sized shallow lakes. Here, using measurements of the water chemistry of 25 Pyrenean mountain lakes and temperature records for 14 of them, we show that the environmental conditions which prevail in their littoral zones have undergone rapid changes between 2007 and 2023. Over this 16-year period, we found that, on average, the duration of the ice-cover period decreased by 58.35 days, and the average annual water temperature rose by 1.65 °C. We also found a significant overall decrease in pH, total organic carbon and nitrogen, as well as a significant increase in hardness and dissolved potassium. Our results demonstrate rapid abiotic environmental alterations in mountain lakes, with potential negative implications for humans, wildlife, livestock and ecosystem functioning. Likely consequences include declines in aquatic biodiversity, a degradation in the quality of drinking water and increased health risks from harmful algal blooms. Policy must urgently acknowledge the impacts of global change in mountains in order to take the necessary management actions.

Drug-resistant infections caused by spores of the mould Aspergillus fumigatus pose a major challenge in managing chronic respiratory disease. Evidence shows that a substantial burden of aspergillosis is caused by strains that have evolved resistance to azole antifungal chemicals in the environment, however the contribution of local exposures to the colonisation of patients remains unclear. To investigate routes of acquisition, we whole-genome sequenced A. fumigatus isolates from individuals with chronic pulmonary fungal disease ( n =182, 15 individuals), their homes ( n =101, 10 homes), and hospital environments ( n =102). These data were then integrated with retrospective sequence datasets enabling phylogenetic resolution across 912 genomes of UK A. fumigatus . We found high genetic diversity in clinical isolates, frequent mixed colonisation, and azole resistance in ~25% of infections, particularly in those patients with cystic fibrosis (CF) and chronic pulmonary aspergillosis (CPA). The TR34/L98H cyp51A resistance allele, a well characterised marker of environmental adaptation to azole agricultural fungicides, was present in 25% of clinical azole-resistant strains. While azole-resistant A. fumigatus was detected in 6/10 homes, phylogenomic analysis revealed no clear genetic link between the home environment and clinical fungal lung isolates. A. fumigatus was prevalent in hospital environments, with azole-resistant isolates comprising 4.5% ( n =9/202) of air and 3.4% ( n =6/178) of soil isolates, predominantly harbouring the TR34/L98H allele. In contrast to homes, phylogenomic and pairwise SNP analysis revealed numerous clinical isolates with >97% genetic identity when compared to those isolated from the hospital environment and randomly chosen pairs of UK isolates. These findings indicate widespread exposure and potential nosocomial acquisition of drug-resistant genotypes of A. fumigatus , supporting the need for targeted environmental surveillance and mitigation of exposures in healthcare settings. ### Competing Interest Statement A. Shah reports consultancy fees from AstraZeneca, Mundipharma and Gilead Sciences, speaker fees from Insmed, and research grants from AstraZeneca, Gilead Sciences and Pfizer. MCF reports speaker fees from Gilead Sciences ### Funding Statement This work was supported by a MRC Clinical Academic Research Partnership fellowship (MR/T005572/1 to AS. AS and MF were further supported by the MRC centre grant (MR/X020258/1). DAJ supported by the Fungal One Health and Anti microbial resistance Network BBSRC BB/Z515619/1 and Cystic Fibrosis Trust Strategic Research Centre SRC015 Targeting Immunotherapy in Fungal Infections in Cystic Fibrosis. MCF, DAJ, APB, JR received funding from Wellcome Trust grant 219551/Z/19/Z. JMGS, SH, RL, MCF received funding from NERC grant NE/X00547X/1. MCF is a fellow in the CIFAR Fungal Kingdoms program ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The London Brent Research Ethics Committee of the United Kingdom Health Research Authority gave ethical approval for this work (REC reference: 19/LO/1663). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

The fungal genus Cryptococcus includes several life-threatening human pathogens as well as diverse saprobic species whose genome architecture, ecology, and evolutionary history remain less well characterized. Understanding how some lineages evolved into major pathogens remains a central challenge and may be advanced by comparisons with their nonpathogenic counterparts. Integrative approaches have become essential for delimiting species and reconstructing evolutionary relationships, particularly in lineages with cryptic diversity or extensive chromosomal rearrangements. Here, we formally characterize six Cryptococcus species representing distinct evolutionary lineages, comprising both newly discovered and previously recognized but unnamed taxa, through a combination of phylogenomic analyses, divergence metrics, chromosomal comparisons, mating assays, and phenotypic profiling. Among pathogenic taxa, we formally name Cryptococcus hyracis sp. nov., corresponding to the previously characterized VGV lineage within the C. gattii complex. In parallel, we describe five saprobic, nonpathogenic species isolated from fruit, soil, and bark beetle galleries, spanning four phylogenetic clades. We identify a strong ecological association with bark beetles for Cryptococcus porticicola sp. nov., the only newly described nonpathogenic species with multiple sequenced strains from diverse sites. In this species, we detect strain-level chromosomal variation and evidence of sexual reproduction, along with population-level signatures of recombination. Across the genus, chromosome-level comparisons reveal extensive structural variation, including species- and strain-specific rearrangements that may restrict gene flow. We also identify multiple instances of chromosome number reduction, often accompanied by genomic signatures consistent with centromere inactivation or loss of centromeric identity. Comparative metabolic profiling with Biolog phenotype microarrays reveals clade-level differentiation and distinct substrate preferences, which may reflect metabolic divergence and habitat-specific diversification. Notably, we confirm that thermotolerance is restricted to clinically relevant taxa. These findings refine the species-level taxonomy of Cryptococcus, broaden its known genomic and ecological diversity, and strengthen the framework for investigating speciation, adaptation, and the emergence of pathogenicity within the genus.

Drug discovery is a collaborative endeavor that often involves scientists from various disciplines and global collaborators. Efficient real-time sharing and updating of design-make-test-analyze (DMTA) information remains a challenge in drug discovery, hindering timely decision-making and project advancement. We propose a novel approach utilizing existing electronic inventory systems as DMTA workflow tracking platforms. Our approach at Sygnature Discovery leverages the inherent flexibility of these systems, allowing us to tailor stages and compound information to individual project needs, resulting in significant cost savings compared with building an in-house solution or purchasing a commercial solution. Given the wide adoption of electronic inventory platforms in drug discovery, our strategy holds immense potential for easy adoption and broad application across the industry.