The research team set out to answer a question that has long frustrated plant pathologists and viticulturists alike: why do some grapevine cultivars tolerate infection by trunk disease fungi while others succumb, even though no grapevine genotype is fully resistant? Tolerance in this context is measured by the expression of foliar symptoms, which varies considerably among cultivars, yet the biochemical mechanisms underlying this variation have remained poorly understood. To probe the question, the researchers chose two cultivars with well-documented contrasting responses to Botryosphaeria dieback: Chardonnay, which shows greater tolerance, and Gewurztraminer, which is more susceptible. By comparing how these two cultivars reconfigure their chemistry after infection, the team hoped to identify the metabolic signatures that separate a resilient vine from a vulnerable one.

The experimental design was ambitious in scope. Rather than examining only the infection site in the woody stem, as most earlier studies have done, the researchers conducted whole-plant metabolomic analyses, sampling wood, leaves and roots at different times after inoculation. They used untargeted liquid chromatography coupled with mass spectrometry, a technique that allows scientists to detect and measure thousands of small molecules simultaneously without knowing in advance which ones will prove important. This unbiased approach is critical when studying complex plant-pathogen interactions, because defense chemistry often involves unexpected compounds and pathways that a targeted analysis would miss entirely.

A key feature of the study was the use of two different N. parvum isolates that differ in aggressiveness. Pathogen colonization assays confirmed that the two isolates possessed contrasting wood invasion capacities, with one spreading more extensively through the host tissue than the other. This distinction mattered: it allowed the researchers to separate the effects of the plant cultivar from the effects of the fungal strain, revealing that the outcome of infection depends on the specific pairing of host and pathogen rather than on a generic interaction between grapevine and wood-decay fungus. The two isolates used in the work were designated Np.Bt67 and Np.Bourgogne, and their differing behavior in the wood provided a natural experiment in fungal virulence.

When the team analyzed the resulting metabolomic data using principal component analysis, a statistical method that reveals the dominant sources of variation in large datasets, a clear pattern emerged. The cultivar of the vine and the identity of the fungal isolate were the main factors structuring metabolic variation across the experiment, with additional contributions from the organ being sampled and the time elapsed since inoculation. In other words, the chemical state of a vine after infection is not determined by the fungus alone or the plant alone, but by the interplay between a particular cultivar and a particular fungal isolate, modulated by where in the plant one looks and how long the infection has had to develop.

The most striking differences appeared in the wood, the primary battleground between vine and pathogen. In response to the most aggressive isolate, the two cultivars mounted clearly distinct metabolic responses, particularly in their profiles of stilbenes and oxylipins. Stilbenes are a family of phenolic compounds, including the famous resveratrol, that grapevines synthesize as antifungal weapons, and their production is governed by enzymes such as stilbene synthase and the upstream phenylalanine ammonia-lyase, both central players in plant defense. Oxylipins, by contrast, are oxygenated derivatives of fatty acids produced through the lipoxygenase pathway, and they serve as both antimicrobial compounds and signaling molecules that coordinate defense responses across the plant.

Here the tolerant cultivar revealed its hand. Compared with Gewurztraminer, Chardonnay showed a faster and stronger induction of stilbene and fatty acid synthesis in its wood, especially of oxylipins, compounds that could be involved in both direct defense and long-distance signaling. This rapid chemical mobilization suggests that the tolerant vine does not simply produce more of the right compounds at the end of the battle; it activates its defensive chemistry earlier and more vigorously, potentially slowing the pathogen before it can establish a firm foothold. Notably, the study found that pathogen growth was similar between the two cultivars, meaning that the difference in tolerance cannot be explained by the fungus simply growing more slowly in Chardonnay. Instead, the two cultivars are characterized by specific metabolite signatures, especially in the wood, pointing to fundamentally different interaction mechanisms rather than a common response to wood decay.

Perhaps the most surprising finding came from beyond the infection site. The researchers observed that leaves and roots also exhibited early metabolic adjustments after the fungus was introduced into the wood, and these systemic changes were more pronounced in Chardonnay than in Gewurztraminer. This indicates that the tolerant cultivar mounts a rapid whole-plant response, reprogramming its metabolism far from where the pathogen is actually attacking. Such systemic metabolic reprogramming may reduce the overall impact of infection on host tissues, priming distant organs to cope with the physiological disruption that trunk disease causes as it progresses. The finding challenges the conventional focus on the wood alone and suggests that the fate of an infected vine is decided, in part, by how quickly the entire plant can reorganize itself.

The broader implications of this work extend into viticulture and breeding. Grapevine trunk diseases are increasingly concerning in the context of climate change, and with no fully resistant genotypes available, growers currently rely on costly and labor-intensive management practices, including the surgical removal of infected wood and the replanting of dead vines. Understanding the metabolic basis of tolerance could eventually help breeders select for cultivars with the rapid stilbene and oxylipin responses seen in Chardonnay, or guide the development of treatments that stimulate these pathways in susceptible varieties. The study also underscores that fungal isolate matters as much as host cultivar, which means that breeding and protection strategies may need to account for the local diversity of Botryosphaeriaceae populations in vineyards.

By integrating pathogen colonization data with untargeted metabolomics across three organs, two cultivars, two fungal isolates and multiple time points, the research provides a more integrated view of grapevine responses to Botryosphaeriaceae infection than has previously been available. The work, conducted at the Université de Haute Alsace with plants supplied by INRAE UMR SVQV in Colmar, France, and supported by the French Ministry of Higher Education and Research, demonstrates that tolerance to trunk disease is not a single trait but a dynamic, system-wide chemical performance. As vineyards face mounting pressure from a warming climate and evolving pathogen communities, studies like this one bring the field closer to understanding why some vines endure what destroys others, and how that resilience might one day be engineered or bred into the varieties the wine world depends on.

Subject of Research: Metabolomic responses of tolerant and susceptible grapevine cultivars to infection by the trunk disease fungus Neofusicoccum parvum

Article Title: Whole plant metabolomic analysis reveals contrasted responses in tolerant and susceptible grapevine cultivars to infection with different isolates of Neofusicoccum parvum, a major trunk disease fungus

Article References: Grau, A. L., Lacrampe, N., Goddard, M.-L., & Chong, J. (2026). Whole plant metabolomic analysis reveals contrasted responses in tolerant and susceptible grapevine cultivars to infection with different isolates of Neofusicoccum parvum, a major trunk disease fungus. BMC Plant Biology. https://doi.org/10.1186/s12870-026-09951-3

Image Credits: AI Generated

DOI: 10.1186/s12870-026-09951-3

Keywords: grapevine, Neofusicoccum parvum, Botryosphaeria dieback, grapevine trunk diseases, metabolomics, stilbenes, oxylipins, plant defense, Chardonnay, Gewurztraminer, fungal pathogen, viticulture

Candidozyma auris has earned a reputation as one of the most concerning healthcare-associated fungal pathogens of the modern era. Unlike many of its fungal relatives, it persists stubbornly in the hospital environment, colonizes surfaces and medical equipment, spreads between patients in healthcare facilities, and frequently displays resistance to the antifungal drugs clinicians rely upon most. First recognized as a human pathogen less than two decades ago, it has since been reported on multiple continents, triggering outbreaks in intensive care units and prompting public health agencies to classify it as a serious global health threat. Its ability to survive routine disinfection and to be misidentified by conventional laboratory methods has made containment exceptionally difficult, and each new clinical dataset contributes valuable intelligence about how the organism behaves in actual patient care.

The Turkish research team set out to answer a question that has divided the field: does C. auris candidemia actually kill more patients than candidemia caused by other Candida species, or does it merely appear more lethal because it disproportionately infects patients who are already gravely ill? To address this, the investigators conducted a single-center retrospective cohort study, identifying every adult patient with candidemia seen at their institution and classifying infections by species. Identification was performed using MALDI-TOF mass spectrometry, a rapid proteomic technique that has become the gold standard for distinguishing C. auris from look-alike yeasts that older biochemical panels frequently confuse with it. Accurate speciation matters enormously here, because misidentification has historically hampered both surveillance and appropriate treatment.

The clinical profiles of the two patient groups differed in telling ways. Patients with C. auris candidemia had spent significantly longer in the hospital before their bloodstream infection developed, a pattern consistent with a healthcare-associated pathogen that colonizes patients during extended stays. They also more frequently had central venous catheters, the indwelling lines that provide fungi with a direct portal into the bloodstream, and greater exposure to corticosteroids, which suppress immune defenses. These exposures are classic risk factors for invasive candidiasis in general, but their heightened frequency in the C. auris group underscores how thoroughly this organism is woven into the fabric of modern intensive medical care. The findings reinforce the picture of C. auris as an opportunist that exploits the very devices and drugs that keep critically ill patients alive.

When the researchers examined crude outcomes, the headline number was striking in its symmetry: 30-day all-cause mortality was 62.3 percent among patients with C. auris candidemia and 62.5 percent among those with non-auris Candida infections, a difference of essentially zero. On the surface, this suggests the emerging pathogen is no deadlier than its established cousins. But crude comparisons in observational data can be deeply misleading, and the investigators knew that the patients harboring C. auris arrived at their infections with a different constellation of vulnerabilities. To disentangle the effect of the organism itself from the effect of patient characteristics, they turned to more sophisticated statistical machinery.

The team employed a multivariable Firth-penalized logistic regression model, a technique designed to produce more stable estimates when outcomes are imbalanced or sample sizes are modest, and they handled missing data through multiple imputation. The model was constructed with clinical input to ensure that the variables adjusted for reflected genuine medical knowledge rather than statistical convenience. After adjustment, C. auris candidemia was associated with higher estimated odds of 30-day mortality, with an adjusted odds ratio of 1.967, meaning the odds of death were nearly doubled relative to non-auris candidemia. However, the 95 percent confidence interval ranged from 0.954 to 4.055 and included the null value of one, with a p value of 0.067, meaning the association fell just short of conventional statistical significance.

To translate the regression results into more intuitive risk terms, the researchers used g-computation to estimate standardized marginal mortality risks. Under this approach, the adjusted 30-day mortality was estimated at 69.7 percent for C. auris candidemia compared with 59.3 percent for non-auris Candida candidemia, corresponding to an adjusted risk difference of 10.4 percentage points, with a confidence interval spanning from minus 0.2 to plus 21.3 points. In other words, once patient severity was accounted for, the data hinted that C. auris infections carry a genuinely elevated mortality burden, potentially adding roughly ten deaths per hundred patients, but the uncertainty around that estimate means the true effect could range from negligible to substantial. The authors are explicit that these findings should be interpreted as associative rather than causal, and that larger prospective multicenter studies across diverse healthcare settings are needed to confirm them.

Beyond the comparison between species, the study identified the factors that independently predicted death within 30 days across the entire cohort. Older age, higher scores on the Sequential Organ Failure Assessment, or SOFA, scale, the presence of septic shock, corticosteroid use, and hemodialysis were all associated with higher adjusted odds of mortality. These determinants are familiar from the broader candidemia literature: they reflect the reality that bloodstream fungal infections are most lethal in patients whose organs are already failing and whose immune systems have been blunted by illness or medication. The consistency of these predictors with prior research lends credibility to the study’s methodology and suggests the dataset behaves as expected, strengthening confidence in the species-specific comparisons.

The antifungal susceptibility findings carry important practical implications for treatment. Among C. auris isolates, echinocandin non-wild-type phenotypes were uncommon, which is welcome news because echinocandins are the recommended first-line therapy for invasive candidiasis and are often the drug class of choice against C. auris. However, elevated minimum inhibitory concentrations for amphotericin B were observed in approximately one-third of tested isolates, a troubling signal for an older but still-used antifungal that clinicians may reach for when first-line options fail or are unavailable. Meanwhile, resistance to fluconazole was frequent among tested Candida parapsilosis isolates, a reminder that antifungal resistance is not confined to the emerging pathogen and that susceptibility testing remains essential for guiding therapy across all Candida species. Susceptibility results were interpreted using applicable EUCAST clinical breakpoints or epidemiological cut-off values, and where no interpretive criteria existed, results were reported descriptively, reflecting the ongoing challenge that interpretive standards for some antifungal-organism combinations are still evolving.

The study’s conclusions are measured but consequential. C. auris candidemia, the authors report, is characterized by a distinct profile of healthcare-associated exposures and a distinct antifungal susceptibility pattern, and while crude mortality appears similar to other candidemia, adjusted estimates point toward higher mortality that remains statistically imprecise. For clinicians, the message is twofold: patients colonized or infected with C. auris deserve vigilant attention to modifiable risk factors such as catheter management and careful stewardship of corticosteroids, and treatment decisions should be anchored in susceptibility data rather than assumptions. For public health officials, the findings add to the accumulating evidence that C. auris is not simply another Candida species but a pathogen with its own epidemiology, its own resistance landscape, and potentially its own mortality penalty. As the global footprint of this fungus continues to expand, studies like this one, grounded in real-world clinical data and rigorous statistical adjustment, will be essential for calibrating the response. The research received no specific funding, was approved by the Etlik City Hospital clinical research ethics committee, and was conducted in accordance with the Declaration of Helsinki, with the requirement for informed consent waived given its retrospective design.

Subject of Research: Comparison of clinical characteristics, antifungal susceptibility, and 30-day mortality in Candidozyma auris versus non-auris Candida candidemia

Article Title: Clinical characteristics, treatment strategies, and factors associated with 30-day mortality in Candidozyma auris versus non-auris Candida candidemia: a retrospective cohort study

Article References: Kuzi, S., Çiçek Şentürk, G., Kul, G., Haykır, A., Yılmaz, N., Korkmaz, N., Bulut, D., Aslan, M., Yapar Toros, G., Şencan, İ., & Tütüncü, E. E. (2026). Clinical characteristics, treatment strategies, and factors associated with 30-day mortality in Candidozyma auris versus non-auris Candida candidemia: a retrospective cohort study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14401-4

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14401-4

Keywords: Candidozyma auris, candidemia, antifungal resistance, 30-day mortality, bloodstream infection, echinocandins, amphotericin B, fluconazole resistance, septic shock, healthcare-associated infection, MALDI-TOF, risk factors