The aim of this review is to provide an in-depth overview of chromoblastomycosis, with emphasis on emerging management strategies and therapeutic options, and to underscore potential gaps in the literature and priorities for future research.

Lotmaria passim is a widespread trypanosomatid parasite of the honey bee gut, yet the metabolic pathways underpinning its growth and infection remain poorly defined. Like other kinetoplastids, L. passim synthesizes ergosterol as its principal membrane sterol, but the functional significance of this pathway in an insect-associated lineage has not been experimentally assessed. We investigated ergosterol biosynthesis in L. passim through phylogenetic analyses, targeted gene disruption, sterol profiling, and honey bee infection assays. Early sterol biosynthetic enzymes displayed non-canonical evolutionary affiliations, whereas late stage enzymes localized to the endoplasmic reticulum. Genetic analyses showed that sterol C-8 isomerase appears to be essential for parasite viability, while sterol C-5 desaturase (SC5D) is dispensable in vitro. SC5D-null mutants (LpΔSC5D) accumulated ergosta-7,22-dienol, confirming its role in the final step of ergosterol synthesis. Although LpΔSC5D grew normally at optimal temperature, they exhibited temperature-sensitive growth defects, abnormal morphology, amphotericin B resistance, and a marked reduction in honey bee gut colonization. These findings demonstrate that while L. passim can tolerate altered sterol composition in culture, intact ergosterol biosynthesis is critical for environmental resilience and successful host infection. Sterol metabolism thus emerges as a key determinant of fitness and infection in this insect-associated trypanosomatid.

Mucormycosis is an opportunistic infection caused by fungi of the order Mucorales, primarily affecting immunocompromised individuals or those with disruption of skin or mucosal integrity. The most common clinical forms include pulmonary, rhino-orbito-cerebral, and cutaneous presentations. We report the case of a patient in his seventh decade of life with a history of diabetes mellitus who presented with a two-month history of paroxysmal cough with mucopurulent sputum, fever, and weight loss. Bronchoscopy and biopsy confirmed the diagnosis of endobronchial mucormycosis, an uncommon clinical presentation, with histopathological findings of sparsely septate, hyaline hyphae. The patient was started on amphotericin B therapy; however, his clinical course was unfavorable, developing multiorgan failure that led to death within 72 hours. Molecular sequencing of the specimen identified Rhizopus homothallicus as the causative agent.

Talaromycosis is an opportunistic fungal infection caused by the thermally dimorphic fungus Talaromyces marneffei. During infection, T. marneffei survives within host phagocytic cells, where it encounters iron restriction and host-derived stress conditions. Therefore, regulation of iron homeostasis is essential for fungal adaptation and pathogenicity. HapX is a conserved bZIP transcription factor involved in iron-responsive regulation in several fungal species, but its role in T. marneffei has not been investigated. In this study, we examined the function of HapX in iron-dependent growth, stress tolerance, intracellular survival, and virulence in T. marneffei. ΔhapX deletion and complemented strains were constructed and analyzed under defined iron conditions in both mold and yeast phases. Deletion of hapX resulted in significant growth defects under iron-limited conditions, whereas growth under iron-replete conditions remained largely unchanged. The ΔhapX mutant showed reduced conidiation and impaired conidial germination. Transcriptional analysis revealed altered expression of iron-responsive genes, including reduced induction of siderophore biosynthesis genes, leading to reduce siderophore production. In addition to iron-dependent growth defects, loss of HapX increased sensitivity to cell wall and membrane stressors and selectively reduced tolerance to nitrosative stress in the yeast phase, while oxidative stress tolerance remained unchanged. The ΔhapX mutant exhibited increased susceptibility to amphotericin B. Importantly, deletion of hapX significantly reduced fungal survival within phagocytic amoeba and attenuated virulence in a Galleria mellonella infection model. Overall, our findings demonstrate that HapX contributes to the coordination of iron homeostasis, stress adaptation, and intracellular survival, which together support pathogenic fitness in T. marneffei.

Leishmania RNA viruses (LRVs) have emerged as significant modulators of disease severity, therapeutic response, and clinical outcomes in various forms of leishmaniasis. This review provides a comprehensive overview of the current knowledge surrounding LRV1 and LRV2, focusing on their taxonomy, molecular biology, epidemiological patterns, and pathogenic roles across Leishmania species. LRV1, predominantly infecting New World Leishmania (Viannia) species such as L. guyanensis and L. braziliensis, and LRV2, primarily associated with Old World species such as L. major, L. tropica, and L. infantum as viral endosymbionts, have both been associated with increased mucocutaneous dissemination, treatment failure, and disease relapse. Mechanistically, these viruses enhance parasite virulence through immune modulation-particularly via Toll-like receptor 3 (TLR3)-leading to chronic inflammation and host tissue damage. The presence of LRV has been correlated with unresponsiveness to first-line treatments such as meglumine antimoniate and amphotericin B, especially in endemic regions. Furthermore, LRV may serve as a prognostic biomarker, and its detection could guide therapeutic decision-making in high-risk patients. The review also discusses emerging therapeutic strategies targeting viral components, such as capsid proteins and RNA-dependent RNA polymerase, as well as vaccine development using recombinant viral antigens. Finally, it emphasizes the urgent need for expanded surveillance, standardized diagnostics, and deeper exploration of host-virus-parasite interactions to better understand the clinical and epidemiological impact of LRV-positive leishmaniasis.

Candiduria, defined as the presence of Candida spp. in urine, is more common among hospitalized patients, particularly those admitted to intensive care units (ICUs). This study aimed to determine the epidemiology, associated risk factors, clinical symptoms, ultrasound findings, and outcomes of empirical antifungal therapy in neonates, infants, and pediatric patients with symptomatic candiduria admitted to neonatal ICU (NICU) and pediatric ICU (PICU) in southern Iran. In this retrospective cross-sectional study, medical records of neonates, infants, and pediatric patients with candiduria admitted to the NICU and PICU of two tertiary-care hospitals in Shiraz, Iran, between March 2012 and March 2022 were reviewed. Data were extracted from the hospital information system. Among 19,900 ICU admissions (3,471 neonates; 4,810 infants; and 11,619 pediatric patients), 400 patients (2.01%) were diagnosed with candiduria. The prevalence was 2.18% (n = 76) in neonates, 1.58% (n = 76) in infants, and 2.13% (n = 248) in pediatric patients. Prematurity was the most common risk factor among neonates (29, 38.15%), whereas urinary catheterization was predominant in infants (41, 53.94%) and history of bacterial urinary tract infection in pediatric patients (165, 66.53%). Hydronephrosis (176, 44%) was the most frequent ultrasound finding. Most patients had an ICU stay of 1-5 days (335, 83.75%), and candiduria was typically diagnosed within the first three days of ICU admission. Fluconazole was the primary empirical antifungal agent, while amphotericin B was administered in selected cases. All patients achieved complete clinical and microbiological resolution following treatment. Our findings indicate that history of bacterial urinary tract infection, urinary catheterization, antibiotic exposure, poor feeding, and hydronephrosis are important predisposing factors for candiduria in critically ill neonates, infants, and pediatric patients. Fluconazole appears to be an effective first-line empirical therapy in this population.

Cysteine proteases are critical drug targets for Trypanosomatids, crucial for the host cell invasion, survival and establishing infection. The current therapeutic regimen for leishmaniasis is inadequate, necessitating the search for safer anti-leishmanial agents. A fourteen-member library of new isoxazole derivatives was synthesised using a 1, 3-dipolar cycloaddition approach and then evaluated for antileishmanial activity. Ligands PB, PM and PE were found most effective against intramacrophage amastigotes of Leishmania donovani with EC50 values of 2.42μM, 2.93 μM and 5.19μM, respectively, compared to Amphotericin-B (IC50 2.15 μM). They also inhibited the promastigote stage of the parasite with an EC50 of 9.44 µM, 11.99µM and 14.81 µM, respectively. Mechanistic in silico studies against cysteine protease, followed by in vitro corroboration using Bz-Arg-AMC hydrochloride fluorogenic peptide substrate ascertained the promising potential of PM (IC50 10.34 μM) as a cysteine protease inhibitor. Compounds fared well in the toxicity screen against THP-1 human monocytic cells. Compounds PB, PM and PE emerged as potent hits, and PM with high activity and low toxicity can be further developed into a potent lead molecule (s) to fight Leishmania donovani. The design of isoxazole-based small molecule libraries presents a promising strategy for the development of safer and potent antileishmanial agents targeting cysteine proteases.

Leishmaniasis is a neglected tropical disease caused by Leishmania parasites and is associated with more than 1.3 million cases annually. The current therapeutic options include pentavalent antimonials, miltefosine, and amphotericin B, but their use is limited because of high toxicity, declining efficacy due to drug resistance, high treatment costs, and the absence of rationally designed, target-based antileishmanial therapies. This critical gap necessitates the discovery of novel, safe, and effective anti-leishmanial agents. In the present study, an E-Pharmacophore-based screening strategy was employed to identify pharmacological alternatives for treating leishmaniasis through a drug repurposing approach. A comprehensive in silico screening of clinically approved molecules was conducted against Leishmania major methionyl-tRNA synthetase (LmMetRS; PDB ID: 6SWX), an essential enzyme in parasite protein biosynthesis and a validated, selective molecular target for antileishmanial drug discovery. Potential hit molecules were identified by pharmacophore-based screening, molecular docking, and molecular dynamics simulations. The virtual screening identified four promising hits: Bofutrelvir, Rebamipide, Selumitinib, and Carvedilol. Additionally, post-simulation and density functional theory (DFT) analysis were performed to evaluate the electronic characteristics of the top two hits (Bofutrelvir, Selumitinib). These candidates demonstrated superior binding interactions within the LmMetRS allosteric site, stable protein-ligand complexes, supporting their therapeutic potential. These findings provide a strong foundation for drug repurposing and highlight these compounds as potential anti-leishmanial agents. Further biological validation is warranted to validate their anti-leishmanial efficacy.

HIV-associated talaromycosis (HAT) is a severe fungal infection for which established severity assessment methods are lacking. The Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores were evaluated in 464 patients with HAT to assess their associations with inflammatory markers, hospital stay, and 30-day mortality. SOFA scores were negatively correlated with blood culture positivity time (r = -0.470, P < 0.001) and positively correlated with IL-6, IL-10, and CRP (all P < 0.001). Patients with fungemia had higher SOFA scores (2.3 ± 2.4 vs. 1.2 ± 0.6, P < 0.001). Mortality increased with qSOFA scores: 8.9% (score 0), 16.5% (score 1), and 55.0% (score ≥2; P < 0.001). For SOFA, mortality was 4.5% (scores 0-1), 6.8% (2-3), 22.0% (4-5), 52.2% (6-7), and 85.7% (≥8; P < 0.001), repectively. Survivors' SOFA scores improved by day 7 (1.6 ± 1.6 to 1.0 ± 1.4, P < 0.001), while non-survivors worsened by day 7 (4.8 ± 3.4 to 5.1 ± 5.6, P = 0.027) compared to day 0. Among the surviving patients, the hospital stay days were 21.0 (14.0-27.0) for scores 0-1, 22.0 (16.0-29.0) for scores 2-3, 27.0 (20.3-43.5) for scores 4-6 and 29.0 (5.5-38.0) for scores ≥6 (P = 0.005). Multivariate analysis identified qSOFA [adjusted odds ratio (AOR):1.564, P = 0.018], SOFA [AOR:1.533, P = 0.001], and non-amphotericin B deoxycholate (non-AmBd) therapy [AOR:2.732, P = 0.026] were independent predictors of 30-day mortality. SOFA and qSOFA both predicted poor outcomes in patients with HAT. Early diagnosis and preemptive AmBd therapy should be prioritized for patients with HAT who had high SOFA/qSOFA scores.