The clinical story began with a neurosurgical procedure. The patient underwent lysis of spinal arachnoid adhesions as treatment for hydrocephalus, a condition in which cerebrospinal fluid accumulates in the brain’s ventricles and raises intracranial pressure. Postoperatively, rather than recovering as expected, she developed progressive dizziness and limb weakness. Contrast-enhanced magnetic resonance imaging revealed meningitis, inflammation of the membranes that envelop the brain and spinal cord. At that stage, her physicians treated her empirically with piperacillin-tazobactam, a broad-spectrum antibiotic combination, for one month. Antibacterial therapy, however, would prove to be aimed at the wrong class of microbe entirely.

Follow-up imaging changed the picture dramatically. The repeat contrast-enhanced MRI showed striking enhancement of the skull base meninges, arranged in a pattern the authors describe as a vividly characteristic Christmas-tree appearance. In neuroradiology, meningeal enhancement along the skull base is a well-recognized sign of chronic infectious or inflammatory disease, but the branching, tree-like configuration documented here is unusual and visually distinctive. Equally important was a second set of findings: the images demonstrated irregular thickening of cerebral vessel walls that took up contrast material, together with irregularity of the vessel lumens themselves. That combination, vessel wall inflammation plus caliber irregularity, pointed toward a vasculitic process capable of blocking blood flow and causing strokes.

That is precisely what happened. The infection developed into multiple hemorrhagic infarcts, areas of brain tissue that died from interrupted blood supply and then bled into the damaged region. Hemorrhagic transformation of infarcts is a feared complication of any cerebral infarction, and in infectious settings it typically reflects direct invasion or inflammation of vessel walls, which weakens them and disrupts the blood-brain barrier. The imaging sequence in this case therefore traced a coherent pathological arc: meningeal infection, spread to the vessels of the circle of brain perfusion, vasculitis, thrombosis or embolization, infarction, and finally hemorrhage within the infarcted tissue.

The decisive diagnostic step came not from microscopy or culture but from metagenomic next-generation sequencing, or mNGS, performed on the patient’s cerebrospinal fluid and blood samples. mNGS is an unbiased technique that extracts all genetic material in a sample and matches it against databases of known organisms, allowing pathogens that are slow-growing, fastidious, or unexpected to be identified without prior suspicion. The sequencing confirmed infection with Talaromyces marneffei, a thermally dimorphic fungus that grows as a mold at ambient temperature and as a yeast inside the human body. The case underscores how mNGS has transformed the workup of central nervous system infections, where conventional cultures frequently fail and empiric therapy cannot wait.

Talaromyces marneffei, formerly classified as Penicillium marneffei, is endemic to Southeast Asia and southern China, where it resides in environmental reservoirs that include bamboo rats and soil. Historically, human disease occurred almost exclusively in people with advanced immunosuppression, particularly those with untreated HIV infection, in whom talaromycosis was a defining AIDS-related illness. In recent years, however, cases have increasingly been reported in individuals without obvious immune defects, and the fungus has become an emerging concern as HIV-negative talaromycosis is recognized more often. Central nervous system involvement is rare even among infected patients, which is why a fully documented case with serial imaging and molecular confirmation carries outsized educational value for clinicians far beyond the endemic zone.

Treatment was initiated once the diagnosis was established. The patient received liposomal amphotericin B at a dose of 150 milligrams once daily for two weeks, the standard induction approach for severe talaromycosis, which targets fungal cell membranes and is the recommended first-line agent for disseminated disease. Despite this appropriate therapy, her consciousness failed to improve. The likely explanation, implicit in the imaging, is that by the time the correct diagnosis was made, the infection had already inflicted irreversible vascular and parenchymal damage. Fungal vasculitis of the brain is notoriously refractory to antifungal drugs, which penetrate inflamed, thrombosed tissue poorly, and hemorrhagic infarcts do not reverse even when the organism is finally suppressed.

The outcome was grim. The patient was discharged at her family’s request with a poor prognosis. The authors of the report, writing from the Department of Radiology, emphasize the imaging findings themselves as the core contribution: the Christmas-tree pattern of skull base meningeal enhancement, the irregular enhancing vessel wall thickening, and the evolution into multiple hemorrhagic infarcts together form a recognizable syndrome that should raise suspicion for intracranial T. marneffei infection in the right clinical context. Recognizing this pattern matters because it can prompt early mNGS testing of cerebrospinal fluid, compressing the diagnostic delay that so often proves fatal in fungal diseases of the brain.

The case also carries broader lessons about post-neurosurgical infections. The patient’s symptoms emerged after spinal arachnoid adhesion lysis, and while the report does not establish the precise route by which the fungus entered the central nervous system, the temporal association illustrates how iatrogenic disruption of protective barriers can open a door to opportunistic organisms. It also highlights the limits of empiric antibacterial therapy: a month of piperacillin-tazobactam provided no benefit against a fungus, and the delay may have allowed the infection to progress from treatable meningitis to destructive vasculitis. For clinicians managing postoperative meningitis that fails to respond to antibiotics, the report argues for early escalation to molecular diagnostics and antifungal coverage.

Published as an open-access case report and conducted in accordance with the Declaration of Helsinki, with ethics approval from the hospital’s committee and written informed consent from the patient’s next of kin, the study is a small piece of evidence by design, a single patient’s course rather than a trial. Yet in rare diseases, single cases are how the collective clinical eye is trained. As imaging techniques sharpen and sequencing costs fall, reports like this one build the pattern library that allows a radiologist in any country to look at an enhancing skull base, see the branches of a Christmas tree, and know that a treatable diagnosis may still be within reach, if only it is pursued in time.

Subject of Research: Imaging features of intracranial Talaromyces marneffei infection progressing to multiple hemorrhagic cerebral infarcts

Article Title: Imaging findings of intracranial Talaromyces marneffei infection developing into multiple hemorrhagic infarcts: a case report

Article References: Chen, X., Jin, Y., Wen, J., & Jiang, B. (2026). Imaging findings of intracranial Talaromyces marneffei infection developing into multiple hemorrhagic infarcts: a case report. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14496-9

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14496-9

Keywords: Talaromyces marneffei, talaromycosis, fungal meningitis, MRI, hemorrhagic infarct, metagenomic next-generation sequencing, cerebrospinal fluid, vasculitis, hydrocephalus, central nervous system infection, amphotericin B, case report

The centerpiece of the work is amphotericin B, or AmB, the polyene macrocyclic antibiotic long regarded as the gold standard for serious fungal disease. AmB’s amphiphilic, amphoteric structure gives it high affinity for ergosterol, the sterol that anchors fungal membranes. By sequestering ergosterol and permeabilizing the membrane, it collapses cellular homeostasis and kills fungi outright, with remarkably low propensity for resistance. But the same drug cannot distinguish fungal ergosterol from the cholesterol in mammalian membranes, a shortcoming that produces the notorious nephrotoxicity that has haunted AmB therapy for decades. It also lacks any inherent ability to calm inflammation or promote tissue repair once the pathogen is gone. The new platform, called ATE nanoparticles, was engineered specifically to resolve both limitations simultaneously.

The design hinges on elegant supramolecular chemistry. The researchers synthesized a trivalent phenylboronic acid derivative, termed T-PBA, by reacting N,N,N′,N′,N″-pentamethyldiethylenetriamine with 4-(bromomethyl)phenylboronic acid. Boronic acids form dynamic boronate ester bonds with ortho- and meta-positioned dihydroxyl groups, and the team exploited this to crosslink T-PBA with epigallocatechin gallate, the catechin from green tea better known as EGCG, while simultaneously encapsulating hydrophobic AmB through its own 1,3-diol groups. Nuclear magnetic resonance, an Alizarin Red S competitive displacement assay, Fourier-transform infrared spectroscopy and ultraviolet-visible spectrophotometry all confirmed the boronate ester network: a new B-O-C stretching band appeared at 1011 cm⁻¹, and AmB’s characteristic 337-nanometer absorption red-shifted to 340 nanometers with pronounced broadening, hallmarks of successful encapsulation.

The resulting particles are uniformly spherical, roughly 100 nanometers in diameter, with a net positive surface charge of about +16.3 millivolts that keeps them stably dispersed through electrostatic repulsion. X-ray diffraction showed the encapsulated AmB adopts an amorphous state, and energy-dispersive X-ray mapping revealed a homogeneous distribution of carbon, nitrogen, oxygen and boron throughout each particle. Crucially, the exposed boronic acid groups of T-PBA bind avidly to the cis-diol-rich polysaccharides, β-glucans and mannans, that carpet fungal cell walls. In confocal microscopy experiments with Rhodamine B-labeled drug and Hoechst-stained Candida albicans, ATE nanoparticles accumulated extensively on fungal surfaces, while free AmB produced almost no detectable signal. This adhesive behavior promises prolonged retention at infected lesions, a decisive advantage on the tear-flushed ocular surface.

What makes the platform genuinely intelligent is its responsiveness to the chemistry of infection. Inflamed, fungus-colonized tissue is locally acidic and rich in reactive oxygen species, and both cues destabilize the boronate ester scaffold. In dialysis release experiments, the nanoparticles leaked AmB slowly at physiological pH 7.4, but at pH 6.0, mimicking the infected microenvironment, more than 90 percent of the cargo was liberated within eight hours. Meanwhile, the EGCG component proved a formidable antioxidant in its own right: the particles scavenged 54.22 percent of ABTS radicals at 120 micrograms per milliliter and over 62.78 percent of DPPH radicals at just 32 micrograms per milliliter, offering a shield for host cells bathed in oxidative stress.

The antifungal performance in vitro was striking. The minimum inhibitory concentration of ATE nanoparticles against C. albicans was 0.16 micrograms per milliliter in AmB equivalents, eightfold lower than free AmB at 1.28 micrograms per milliliter. At 2 micrograms per milliliter, the particles eradicated more than 99 percent of fungi within four hours, and scanning electron microscopy revealed the most pronounced morphological collapse and surface wrinkling among all treatment groups. Control particles carrying only EGCG showed no intrinsic fungicidal activity, confirming that the killing power still flows from AmB, now delivered with far greater efficiency. The platform also dismantled biofilms, the self-produced exopolymeric fortresses that shield fungi from drugs and immune attack. Treatment reduced immature biofilm thickness from 30.98 to 9.19 micrometers, cut biomass by 77.44 percent, and suppressed 99.98 percent of fungal growth; against mature, two-day-old biofilms, the particles eradicated over 79.54 percent of biomass and 99.9 percent of viable C. albicans.

The anti-inflammatory half of the story proved equally compelling. In human corneal endothelial cells stressed with hydrogen peroxide, ATE nanoparticles cleared more than 90 percent of intracellular reactive oxygen species, outperforming formulations lacking EGCG. In lipopolysaccharide-stimulated RAW 264.7 macrophages, the particles significantly suppressed the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 while markedly upregulating the anti-inflammatory cytokine IL-10. Cytocompatibility testing underscored the safety gain: at 8 micrograms per milliliter of AmB equivalent, free AmB drove cell viability below 60 percent, whereas the nanoparticle formulation kept viability above 80 percent, effectively detoxifying the gold-standard drug.

In vivo, the team tested the particles in a murine model of C. albicans keratitis and in infected skin wounds. On the eye, fluorescently labeled nanoparticles lingered far longer than free dye, retaining roughly 12.6 percent of the applied dose at eight hours and 5.6 percent at sixteen hours. Over fifteen days of follow-up, treated mice recovered corneal transparency with a clinical grading score of 6, compared with 14 in untreated controls and 8 for AmBisome, the clinically used liposomal AmB formulation. Optical coherence tomography showed corneal thickness falling to 93.6 micrometers in the treated group versus 185.9 micrometers in controls, in vivo confocal microscopy revealed a marked reduction of fungal hyphae, and fungal plate counts confirmed the lowest residual burden of any group. Histology documented restored corneal architecture, downregulated IL-1β and IL-6, and dense, well-aligned collagen deposition indicative of genuine tissue regeneration rather than mere scarring.

The skin wound model told a parallel story. By day eight, wounds treated with ATE nanoparticles had contracted to 18.23 percent of their original area, with near-complete re-epithelialization, compared with 38.74 percent in untreated controls, and collagen fiber deposition reached approximately 2.2-fold that of controls. Biosafety assessments were thorough and reassuring: slit-lamp examination, fluorescein staining, optical coherence tomography and confocal microscopy found no corneal irritation or endothelial cell loss even after seven consecutive days of administration, while blood counts, liver enzymes and kidney markers remained within normal ranges, and major organs showed no pathological lesions. The authors caution that the work remains at the preclinical stage, but the convergence of targeted adhesion, dual-triggered drug release, immunomodulation and demonstrated superiority over an existing clinical formulation marks ATE nanoparticles as a promising template for the next generation of antifungal nanotherapeutics, one that treats the infection and the inflammatory fire it ignites as a single, inseparable problem.

Subject of Research: Amphotericin B-loaded polyphenolic nanoparticles for simultaneous antifungal eradication and immunomodulation in superficial fungal infections

Article Title: Amphotericin B-loaded polyphenolic nanoparticles for synchronous fungal eradication and immunomodulation in treating superficial fungal infections

Article References: Chen, Y., Chen, F., Wang, S., Dai, W., Jin, Q., Jia, F., & Ye, Y. (2026). Amphotericin B-loaded polyphenolic nanoparticles for synchronous fungal eradication and immunomodulation in treating superficial fungal infections. Materials Today Bio, 41, Article 103707. https://doi.org/10.1016/j.mtbio.2026.103707

Image Credits: AI Generated

DOI: 10.1016/j.mtbio.2026.103707

Keywords: amphotericin B, nanoparticles, EGCG, fungal keratitis, Candida albicans, boronate ester, drug delivery, biofilm, anti-inflammatory, polyphenols, nanomedicine, tissue repair

The fungus at the center of the study is Trichophyton rubrum, the dermatophyte most commonly responsible for ringworm and other superficial skin, hair, and nail infections in humans. Dermatophytes are among the most prevalent fungal pathogens worldwide, yet surprisingly little is known about whether they harbor mycoviruses and whether those viruses influence their behavior. To address this gap, the research team first screened clinical isolates of Trichophyton species for the presence of mycoviruses. They then turned to an experimental strategy that has rarely been applied to dermatophytes: heterologous transfection, the deliberate introduction of a virus from one host species into an entirely different one.

The virus chosen for the experiment was Terfezia claveryi endornavirus 1, abbreviated TcEV1, originally described in the desert truffle Terfezia claveryi. Endornaviruses form a distinctive group among mycoviruses. They possess double-stranded RNA genomes, lack the capacity to produce conventional virus particles, and are typically transmitted vertically through cell division and spores rather than spreading horizontally between individuals. Because of these properties, endornavirus infections are often described as cryptic, meaning they persist permanently within host lineages without producing virions or obvious symptoms. This cryptic lifestyle has made it difficult to assess what, if anything, endornaviruses do to their hosts, and has left open the question of whether they can jump between fungal species in nature or in the laboratory.

By introducing TcEV1 into T. rubrum through heterologous transfection, the researchers created a unique experimental system: a human pathogenic fungus carrying a viral passenger from a distant fungal lineage. The comparison between virus-free and virus-infected isolates of the same fungus allowed the team to isolate the specific effects of the virus from the background of the fungus’s own genetics. This controlled design is critical in mycovirus research, where differences between fungal strains can easily be mistaken for viral effects if the comparison is not carefully constructed.

The phenotypic consequences of TcEV1 infection were striking. Under laboratory conditions at 30 degrees Celsius, a temperature favorable to dermatophyte growth, the virus-infected isolate displayed increased radial growth compared with its virus-free counterpart. Radial growth rate is a standard measure of fungal fitness in vitro, reflecting how quickly a colony can expand across a substrate. The infected isolate also showed a significant rise in conidiation capacity, meaning it produced more conidia, the asexual spores through which dermatophytes spread from host to host and from lesion to lesion. Enhanced spore production could plausibly translate into greater transmissibility in a clinical setting, since the infectious dose of dermatophytes depends on the number of viable conidia shed by an infected individual.

The most consequential result, however, emerged from the in vivo experiments. Using a murine skin infection model, the researchers compared the ability of virus-free and TcEV1-infected T. rubrum to colonize living skin tissue. The virus-infected isolate achieved a fungal load approximately 2.5 times higher than the virus-free isolate. This roughly two-and-a-half-fold increase in fungal burden indicates that the presence of the endornavirus substantially enhanced the fungus’s capacity to establish and maintain infection in host tissue. The authors describe this as the first evidence of mycovirus-mediated enhanced virulence in T. rubrum, a finding that reframes mycoviruses from biological curiosities into potential modifiers of human disease severity.

Compounding the picture of heightened pathogenic potential, TcEV1 infection was also associated with reduced susceptibility to two major classes of antifungal agents: the echinocandins and amphotericin B. Echinocandins inhibit the synthesis of beta-glucan, a key structural component of the fungal cell wall, and are a mainstay of systemic antifungal therapy, while amphotericin B binds ergosterol in the fungal membrane and remains one of the most broadly active antifungal drugs available. A shift toward reduced susceptibility in a virus-carrying isolate suggests that mycoviral infection could complicate the treatment of dermatophytosis, although the study’s observations were made in vitro and the clinical implications for patients would require further investigation.

The mechanistic basis for these changes remains an open question. Endornaviruses encode RNA helicase motifs and other replication-associated proteins, and their persistent double-stranded RNA replicative form is a well-known trigger of antiviral responses in many host systems. In fungi, chronic viral infection can reshape metabolism, stress responses, and gene regulation in ways that alter growth and virulence. In plant-associated fungi, mycoviruses have been documented to attenuate virulence, as in the famous case of chestnut blight hypovirulence, but examples of mycoviruses increasing the pathogenicity of a human fungal pathogen are exceedingly rare. The T. rubrum system therefore offers a valuable platform for dissecting how a persistent RNA virus reprograms a dermatophyte’s physiology, from cell wall architecture to spore development and interaction with host tissue.

The study also carries broader implications for how mycologists and clinicians think about fungal disease. If cross-species transmission of mycoviruses can convert a cryptic infection into a driver of enhanced virulence and drug tolerance, then the viral status of clinically important fungi becomes a variable worth monitoring. Screening for mycoviruses could one day complement conventional susceptibility testing, particularly for isolates that behave unusually in the clinic. The finding that an endornavirus from a truffle-associated fungus can establish itself in a dermatophyte also hints that the boundaries between mycoviral host ranges may be more permeable than previously assumed, raising the possibility that such transfers occur in natural settings where fungi share environments.

The research originated from the master’s thesis of Aysenur Simsek at Dokuz Eylul University’s Institute of Science and was supported by the Scientific and Technological Research Council of Türkiye under project number 122Z630 and by Dokuz Eylul University under project number FYL-2025-3680. The corresponding authors are Tetiana Krupodorova of the National Academy of Sciences of Ukraine in Kyiv and Ergin Sahin of Dokuz Eylul University. As the first demonstration that heterologous transfection of an endornavirus can enhance the virulence of a major human dermatophyte both in culture and in a living host, the work opens a new chapter in the study of fungal viruses, one in which the invisible RNA passengers of fungi may help determine how aggressively those fungi infect us and how well our drugs work against them.

Subject of Research: Mycovirus-mediated enhancement of virulence and antifungal resistance in the dermatophyte Trichophyton rubrum

Article Title: Heterologous transfection of an endornavirus alters the phenotype of Trichophyton rubrum in vitro and in vivo

Article References: Simsek, A., Ozturk, N., Akata, I., Batir, M. B., Kaya, S., Kaya, E., Krupodorova, T., Sevindik, M., Edis, G., & Sahin, E. (2026). Heterologous transfection of an endornavirus alters the phenotype of Trichophyton rubrum in vitro and in vivo. Virology Journal. https://doi.org/10.1186/s12985-026-03295-y

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03295-y

Keywords: mycovirus, endornavirus, Trichophyton rubrum, dermatophytosis, TcEV1, heterologous transfection, virulence, antifungal resistance, echinocandins, amphotericin B, murine infection model, double-stranded RNA

The platform was created using electrospinning, a technique in which a polymer solution is subjected to a high electric field and drawn into continuous fibers that collect as a soft, porous mat. The researchers, led by Divya Mathew, Benny Thomas, Sudheep Nagamangalam and Radhakrishnan Edayileveettil Krishnankutty, systematically optimized the polymer concentration, the amount of drug loaded into the spinning solution, and the electrospinning parameters themselves. The goal was to produce fibers that were uniform and free of the bead-like defects that plague poorly tuned electrospinning. Their optimized mats consisted of bead-free poly(vinyl alcohol) nanofibers with an average diameter of roughly 250 nanometers, fine enough to create an enormous surface area for contact with infected tissue while remaining robust enough to handle.

One of the most striking numbers in the study is the entrapment efficiency: the fibers captured 88.6 percent of the amphotericin B, give or take about two percent. That matters because amphotericin B is both expensive and toxic, and any drug that leaks out or fails to incorporate into the carrier is wasted payload that could cause collateral damage. To understand how the drug was held within the polymer, the team turned to Fourier Transform Infrared spectroscopy, which revealed molecular-level interactions between amphotericin B and the poly(vinyl alcohol) matrix through hydrogen bonding. Transmission Electron Microscopy confirmed that the drug was dispersed homogeneously throughout the fiber network rather than clumped into crystals, a detail that helps explain the smooth, predictable release behavior that followed.

The physical character of the mats proved equally important to their function. The optimized fibers showed improved mechanical strength, a moderate hydrophilicity reflected in a water contact angle of about 50 degrees, and an excellent balance between swelling and moisture retention. In practical terms, when the mat is placed on moist skin or mucosal tissue, it hydrates gradually without dissolving too quickly or drying out, maintaining the conditions needed for controlled drug diffusion over an extended period. The researchers also tracked how the material degrades, finding a gradual weight loss of 28.6 percent after fourteen days. That slow biodegradation profile means the mat remains structurally functional throughout the treatment window rather than falling apart prematurely.

To quantify how the drug escapes the matrix, the team fitted their release data to established mathematical models of drug diffusion. The kinetics matched the Korsmeyer–Peppas and Peppas–Sahlin models best, with coefficients of determination above 0.98. This fit pointed to a non-Fickian diffusion mechanism, meaning drug release is governed not simply by molecular diffusion through the polymer but by a combination of diffusion and the relaxation of the polymer chains themselves as they swell. For a topical delivery system, that coupling is advantageous: it smooths out the release profile, avoiding the sharp burst of drug that can irritate tissue and instead providing the sustained exposure needed to suppress fungal regrowth between applications.

Safety was assessed with a battery of cytocompatibility and blood-contacting assays. Three different human cell lines—normal human dermal fibroblasts, keratinocytes of the HaCaT line, and HEK 293 cells—all maintained viability above 80 percent when exposed to the material, and hemolysis testing showed red blood cell rupture remained below five percent. Those thresholds are meaningful benchmarks in biomaterials research, suggesting the mats would not damage the skin cells they are meant to protect nor harm blood components if used on wound beds. For a drug as harsh as amphotericin B, whose systemic use is shadowed by nephrotoxicity, confining it to a local, well-tolerated depot is a strategy aimed squarely at keeping the drug’s benefits while leaving its systemic toxicity behind.

The antifungal performance was tested against three clinically relevant organisms: Candida albicans, the yeast responsible for most mucocutaneous candidiasis, and two filamentous fungi, Aspergillus niger and Aspergillus flavus. The mats produced sustained yet potent inhibition of all three. Just as importantly, the researchers evaluated activity against biofilms—the organized microbial communities encased in a protective extracellular matrix that make infections on catheters, wounds, and mucosal surfaces so difficult to eradicate. Biofilm cells are famously tolerant of antifungals that readily kill their free-floating planktonic counterparts. The amphotericin B-loaded mats cut the metabolic activity and biomass of fungal biofilms by roughly 60 percent compared with untreated controls, a substantial reduction that suggests the platform could help break the cycle of persistent, treatment-resistant surface infections.

The broader significance of the work lies in how it reframes an old drug for a persistent clinical problem. Amphotericin B has been in use for some sixty years, and while lipid formulations such as AmBisome have reduced its toxicity for systemic treatment, options for localized delivery to skin, mucosa, and wounds remain limited. Nanofiber mats offer a distinctive combination of properties for that niche: they conform to irregular surfaces, their porosity supports moisture balance, and their structure can be tuned to control release kinetics. Because poly(vinyl alcohol) is water-soluble, biocompatible, and already familiar in biomedical applications such as wound dressings, the barrier to translating the platform is arguably lower than for more exotic carrier chemistries.

The authors suggest the system is a promising localized antifungal delivery strategy for mucocutaneous and wound-associated infections, offering prolonged drug release, enhanced biocompatibility, and reduced toxicity in a single material. Much work remains before such a mat could reach patients—scale-up of electrospinning, in vivo efficacy studies, and regulatory evaluation all lie ahead. But the study demonstrates, with careful characterization at every step, that a humble polymer spun into nanofibers can tame one of medicine’s most toxic antifungals and turn it into a steady, localized weapon against the fungi and biofilms that resist conventional treatment. In an era of rising antifungal resistance, giving established drugs new delivery formats may be one of the most practical paths forward.

Subject of Research: Electrospun poly(vinyl alcohol) nanofiber mats for sustained topical delivery of amphotericin B with enhanced antifungal and antibiofilm efficacy

Article Title: Electrospun poly(vinyl alcohol) nanofiber mats as a biocompatible platform for sustained topical delivery of Amphotericin B with enhanced antifungal and antibiofilm efficacy

Article References: Mathew, D., Thomas, B., Nagamangalam, S., & Krishnankutty, R. E. (2026). Electrospun poly(vinyl alcohol) nanofiber mats as a biocompatible platform for sustained topical delivery of Amphotericin B with enhanced antifungal and antibiofilm efficacy. Polymer Bulletin, 83(11), Article 638. https://doi.org/10.1007/s00289-026-06681-2

Image Credits: AI Generated

DOI: 10.1007/s00289-026-06681-2

Keywords: Amphotericin B, poly(vinyl alcohol), electrospun nanofibers, sustained drug release, antifungal, antibiofilm, Candida albicans, Aspergillus, biocompatibility, drug delivery, wound infections, Korsmeyer–Peppas

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

L. martiniquensis has attracted growing concern in Southeast Asia as an emerging cause of visceral leishmaniasis, a disease that can be fatal particularly among patients with advanced HIV infection whose immune systems cannot contain the parasite. Amphotericin B remains a mainstay of therapy, yet clinicians in Thailand have documented relapse and treatment failure in patients infected with this species, raising the possibility that some parasite populations carry or acquire reduced susceptibility to the drug. Until now, the molecular machinery underlying such reduced susceptibility in L. martiniquensis has remained largely unexplored, making paired isolates drawn from the same patient at different clinical time points an unusually valuable window into how the parasite changes under drug pressure.

The research team, led by investigators at Chulalongkorn University in Bangkok in collaboration with Hatyai Hospital and King Chulalongkorn Memorial Hospital, obtained one isolate before treatment, designated CULE7.2, and a second, CULE8, after the patient relapsed. They first confirmed the biological difference between the two isolates using in vitro susceptibility assays: CULE8 displayed significantly higher half-maximal and 90 percent inhibitory concentrations of amphotericin B than CULE7.2, with the dose-response curve shifted markedly to the right. Transmission electron microscopy of CULE7.2 promastigotes exposed acutely to the drug revealed the expected cellular damage, including prominent cytoplasmic vacuolization, lipid-like inclusions, mitochondrial swelling, and focal disruption of the nuclear membrane, consistent with amphotericin B’s mechanism of binding membrane sterols and destabilizing cellular membranes.

To explore the transcriptional landscape underlying these phenotypic differences, the researchers profiled both isolates across two developmental stages of the parasite, promastigotes and axenic amastigotes, using RNA sequencing. Importantly, the two isolates were cultured under different conditions: CULE8 was maintained under continuous exposure to a sublethal 0.3 micromolar concentration of amphotericin B, while CULE7.2 was cultured in parallel without the drug. Differential expression analysis, hierarchical clustering, and functional enrichment were performed independently within each stage. This design choice means the observed patterns likely reflect a combination of intrinsic isolate-associated characteristics and the transcriptional response to ongoing drug exposure, an important caveat the authors emphasize in interpreting their results.

In the promastigote stage, the post-relapse isolate CULE8 showed predominant downregulation of genes involved in sterol and lipid metabolism, membrane transport, protein synthesis, motility, and broader metabolic and regulatory processes. Among the affected genes were sterol C24 reductase, an enzyme central to the parasite’s membrane sterol composition and a known determinant of amphotericin B activity, together with upstream enzymes of the mevalonate pathway. At the same time, CULE8 promastigotes displayed increased expression of genes associated with thiol-based redox homeostasis, suggesting a shift toward enhanced management of oxidative stress, a plausible countermeasure to drug-induced membrane and mitochondrial damage.

The axenic amastigote stage, the form that proliferates inside the mammalian host, told a different story. Here, CULE8 showed increased expression of genes linked to lipid metabolism, redox homeostasis, protein synthesis, and proteostasis, alongside broader downregulation of transport genes and genes involved in genome maintenance. Despite the predominantly stage-specific patterns, a small subset of genes showed concordant regulation across both life stages, including genes involved in lipid metabolism and transport. Genes tied to thiol-based redox homeostasis stood out for their elevated expression in both stages, marking this antioxidant capacity as a consistent candidate feature of the relapse-associated parasite and a potential target for functional validation studies.

The virological dimension of the study may prove equally consequential. De novo assembly of RNA-seq reads that failed to map to the parasite genome recovered complete L and S genomic segments of a genetically distinct leishbuvirus from CULE8. This represents, to the authors’ knowledge, the first molecular characterization of a leishbuvirus in a Southeast Asian L. martiniquensis isolate, expanding the known geographic and host range of these viruses. Comparative structural modeling using predicted aligned error matrices supported conservation of the RNA-dependent RNA polymerase core and its Motif C between the CULE8 virus and a reference variant, while negative-stain transmission electron microscopy revealed structures consistent with virus-like particles. Viral RNA abundance was higher in CULE8 than in CULE7.2 across both developmental stages.

The significance of leishbuviruses remains a subject of active debate in the field. Related viruses, including Leishmania RNA virus 1, have been associated in some studies with heightened virulence and treatment failure in other Leishmania species, particularly through modulation of the host inflammatory response, although such associations are not universal and their mechanisms are incompletely understood. The authors are careful to note that the higher leishbuvirus RNA abundance observed in the post-relapse isolate has no established causal relationship with reduced amphotericin B susceptibility or with the patient’s clinical relapse. The finding is best viewed as an observation warranting further investigation in independent isolates rather than as evidence of a viral driver of drug resistance.

Indeed, the authors frame the entire study as hypothesis-generating. Because the paired isolates were examined under different drug-exposure conditions, the transcriptional differences they report cannot be attributed cleanly to either intrinsic isolate biology or adaptive response to amphotericin B, and the findings will require validation in independent isolates under matched experimental conditions. Nevertheless, the breadth of the observed changes, encompassing sterol biosynthesis, lipid handling, membrane transport, redox metabolism, protein homeostasis, and genome maintenance, broadens the molecular landscape associated with reduced amphotericin B susceptibility in this species and identifies multiple candidate pathways for future functional studies, including gene knockout or overexpression experiments that could disentangle correlation from causation.

For a disease that disproportionately strikes immunocompromised patients in resource-limited settings, the stakes of understanding amphotericin B failure are high. Visceral leishmaniasis caused by L. martiniquensis in Thailand is emerging in HIV-coinfected populations, and the therapeutic arsenal is narrow. By pairing rigorous susceptibility testing and ultrastructural imaging with stage-resolved transcriptomics and sensitive viral discovery, this study demonstrates how a single patient’s clinical course can illuminate molecular processes that no laboratory strain could fully recapitulate. The identified candidate pathways, from mevalonate-dependent sterol metabolism to thiol-based antioxidant defenses, now provide concrete starting points for the functional experiments and epidemiological surveillance needed to determine how widespread reduced drug susceptibility might be, and whether hidden viral passengers within these parasites play any role in the clinical outcomes that matter most to patients.

Subject of Research: Transcriptomic analysis of paired Leishmania martiniquensis clinical isolates to identify molecular pathways associated with reduced amphotericin B susceptibility

Article Title: Transcriptomic profiling of paired clinical Leishmania (Mundinia) martiniquensis isolates reveals candidate pathways associated with reduced amphotericin B susceptibility and identifies a novel leishbuvirus variant

Article References: Phadungsaksawasdi, K., Pongpanich, M., Yuanlae, S., Lerona, P. G. E., Sricharoensuk, C., Songumpai, N., Siriyasatien, P., Asawanonda, P., Shotelersuk, V., & Preativatanyou, K. (2026). Transcriptomic profiling of paired clinical Leishmania (Mundinia) martiniquensis isolates reveals candidate pathways associated with reduced amphotericin B susceptibility and identifies a novel leishbuvirus variant. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07628-2

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07628-2

Keywords: Leishmania martiniquensis, Mundinia, amphotericin B, drug susceptibility, transcriptomics, leishbuvirus, visceral leishmaniasis, Thailand, RNA sequencing, parasite virome, sterol metabolism, redox homeostasis