Search Results (496)

Oil palm is a major commodity crop in Southeast Asia, particularly in Malaysia and Indonesia, but its productivity is severely threatened by basal stem rot (BSR) and upper stem rot (USR) caused by the white-rot fungus Ganoderma boninense. Infected palms can lose up to 80% yield and die within 6–24 months (young) or 2–3 years (mature). Despite extensive field management efforts, disease incidence continues to rise, especially after replanting. Understanding infection mechanisms and validating fungal virulence factors are crucial for effective control, yet functional genomics in G. boninense has been limited. Previous RNAi-based gene silencing provided initial insights but was constrained by off-target effects and transient activity. Here, we report the first successful application of CRISPR/Cas9 genome editing in G. boninense for functional gene studies. Two genes were targeted: pyrG, essential in uridine monophosphate (UMP) biosynthesis; and hyd-2, encoding a hydrophobin, a potential virulence determinant implicated in host invasion. The disruption of pyrG produced a uracil auxotroph, and the knockout was validated by screening on 5-FOA and validated our system as a functional molecular tool. Disruption of hyd-2 reduced infection capability of the fungus by ~72% to ~91% in vitro. Mutations in both gene disruptions, including insertions, deletions, and substitutions, were confirmed by sequencing. Sequencing analysis also revealed incomplete editing events, as wild-type gene sequences were detected alongside edited alleles in the mutants. Future enhancements should focus on improving editing efficiency of the system. This work establishes a robust platform for functional genetic analysis and dissecting pathogenicity in G. boninense, ultimately advancing strategies to mitigate basal stem rot disease in oil palm. Full article

Background: Candida albicans constitutes part of the normal human gastrointestinal (GI) microbiome(GM). Alterations inthe GM induced by antibiotics may disrupt colonization resistance and promote fungal overgrowth. This review summarizes the effects of antibiotics on GI C. albicans colonization in experimental animal models and humans. Methods: A narrative review was conducted using data from the PubMed/MEDLINE and Scopus databases. Studies evaluating changes in GI C. albicans populations following antibiotic administration in mice or humans were included. Results: Twenty-six articles met the inclusion criteria, comprising 16 murine and 10 human studies. Across all studies, antibiotics were consistently associated with increased GI C. albicans colonization. The greatest increases were observed with broad-spectrum agents with activity against anaerobic bacteria. Elevated fungal concentrations frequently persisted after treatment discontinuation. Human studies largely reproduced findings from murine models. Despite substantial increases in GI colonization, dissemination beyond the GI tract was uncommon. Conclusions: Available evidence demonstrates that antibiotic-induced disruption of the GM promotes GI overgrowth of C. albicans. Hence, C. albicans concentration can serve as an indicator of antibiotics’ impact on the GM. While increased colonization alone rarely results in invasive disease, antibiotic-associated yeast expansion may represent an important step in the pathogenesis of disseminated candidiasis. Full article

Candida infections represent a major global public health challenge and remain among the most common opportunistic fungal infections worldwide. Although Candida albicans remains the predominant pathogen, the incidence of infections caused by non-albicans species, particularly Candidozyma auris, has increased substantially in recent years. Candida infections range from superficial mucocutaneous disease to invasive life-threatening infections associated with high morbidity and mortality. In addition to clinical burden, growing evidence indicates a substantial negative impact on health-related quality of life, particularly among patients with recurrent vulvovaginal candidiasis and chronic fungal infections. Full article

Fragrant pear canker, caused by Cytospora pyri, is a major branch disease that reduces the productivity and longevity of Korla fragrant pear orchards in Xinjiang, China. During infection and lesion expansion in woody tissues, C. pyri must breach the host cell wall barrier, in which pectin degradation plays a central role by weakening intercellular adhesion and disrupting tissue integrity. Members of glycoside hydrolase family 28 (GH28), represented mainly by polygalacturonases and other pectin-degrading enzymes, are closely involved in fungal invasion and colonization. However, the composition and virulence-related functions of this gene family encoding for these enzymes in C. pyri remain unclear. In this study, GH28 genes were systematically identified and comparatively analyzed in C. pyri and closely related Cytospora species. Infection-stage expression profiling and functional validation were then performed to assess their roles in pathogenicity. A total of 73 GH28 genes were identified across five Cytospora species, including 15 in C. pyri. Most C. pyri GH28 proteins were predicted to be acidic, hydrophilic, extracellularly secreted proteins carrying conserved motifs. Phylogenetic analysis showed that C. pyri GH28 members were closely related to homologs from C. mali. Genomic distribution analysis revealed that these genes were dispersed across multiple scaffolds, with no obvious tandem duplication events. RT-qPCR analysis showed that all seven candidate GH28 genes were induced during infection of fragrant pear branches, with VP1G_08835 and VP1G_03209 exhibiting strong expression responses at 6 dpi. Functional validation further showed that deletion of VP1G_08835 impaired vegetative growth and reduced lesion length on detached pear branches by 26.62% compared with the wild type, whereas complementation restored these phenotypes. These findings demonstrate that GH28 genes participate in C. pyri infection and identify VP1G_08835 as an important GH28 member required for normal growth and contributing to virulence. Full article

Background: Growing interest in the gut mycobiome has renewed focus on Candida spp. in inflammatory bowel disease (IBD). Yet, fecal detection remains difficult to interpret, given its uncertain relationship with intestinal inflammation. This narrative review synthesizes historical, mechanistic, observational, and interventional evidence to distinguish colonization, relative abundance, mucosal invasion, virulence transitions, and potential contributions to IBD. Methods: PubMed, Scopus, the Cochrane Library, and Google Scholar were searched, focusing on human studies and major mechanistic or interventional contributions. The final synthesis included 43 studies, 41 research articles, and two historical monographs. Results: Fungal alterations in IBD are heterogeneous and method-dependent across studies. Longitudinal cohorts have associated increased relative abundance of the genus Candida with active disease, but findings have not been consistently replicated across populations. Experimental evidence suggests that fungal expansion, morphology, and strain-specific virulence may trigger inflammation in selected settings, although stool sequencing cannot establish viability, invasion, morphology, or causality. Antifungal therapy, fecal microbiota transplantation, and nutraceutical approaches may modify microbial or inflammatory markers, but consistent clinical benefits remain unproven. Conclusions: Fecal detection of Candida spp. should generally be interpreted as a context-dependent signal of disrupted bacterial–fungal–immune interactions, not as evidence of infection or a compelling indication for antifungal treatment. Full article

Non-HIV Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic fungal pneumonia that may progress rapidly in immunocompromised hosts. Broad bronchoalveolar lavage fluid (BALF) molecular testing supports microbiologic recognition, but additional organisms often require bedside adjudication. We conducted a single-center observational study of 49 HIV-negative adults with clinically confirmed PJP, routine BALF metagenomic next-generation sequencing support, and complete 30-day follow-up. Diagnosis required compatible symptoms and chest computed tomography findings, microbiologic support for P. jirovecii, and infectious disease specialist exclusion of isolated colonization. The primary endpoint was ICU-level care requirement, defined as ICU admission, invasive mechanical ventilation, or 30-day all-cause mortality. Recent immunosuppressive exposure was present in 48 patients (98.0%). ICU-level care was required in 15 patients (30.6%); all ventilation and death events occurred in this group, and 30-day mortality was 10.2%. Baseline PaO2/FiO2 < 200 mmHg was associated with higher proportions of ICU admission, mechanical ventilation, and death. Chronic kidney disease, lower creatinine clearance, higher lactate dehydrogenase, and bacterial co-pathogen context showed exploratory signals, whereas overall co-pathogen positivity was heterogeneous. These findings support integrating oxygenation status, host vulnerability, and conservative co-pathogen adjudication to guide escalation and antimicrobial decisions after BALF testing. Full article

Background: The clinical presentation of nasal mucosal necrosis, an exceedingly rare manifestation of secondary antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus, often mimics invasive fungal sinusitis (IFS), causing diagnostic challenges and potentially unnecessary surgical interventions. Here, we report a unique case of nasal necrosis exacerbation by thrombopoietin receptor agonist (TPO-RA) therapy. Case Description: A 54-year-old woman with systemic lupus erythematosus and APS developed rapid nasal mucosal necrosis after receiving TPO-RA. An initial clinical suspicion of IFS led to emergency surgical debridement, and histopathology revealed fibrin-rich intraluminal microthrombi without fungal elements. After replacing eltrombopag with fostamatinib (a Syk inhibitor), the nasal lesions improved markedly, with complete mucosal healing. Conclusions: Nasal mucosal necrosis, a rare but serious symptom of secondary APS, requires careful differential diagnosis from IFS or other necrotizing diseases. APS-related vasculopathy should be considered following TPO-RA therapy, particularly if repeat debridement fails to identify an infectious cause. Full article

Invasive candidiasis, predominantly driven by multidrug-resistant Candida species and intractable biofilms, represents an escalating global health crisis with mortality rates rivaling major infectious diseases. The clinical efficacy of conventional antifungal agents—azoles, polyenes, and echinocandins—is severely compromised by poor tissue penetration, dose-limiting systemic toxicity, and the rapid evolution of complex resistance mechanisms. Here, we review the two-decade structural evolution of nanotechnological interventions designed to overcome these pharmacological and biological barriers. We systematically analyze advanced nanosystems, including lipid-based formulations, natural polymers, and biogenic metallic nanostructures, highlighting their capacity to penetrate the dense extracellular polymeric substance (EPS), combat potential fungal ‘nano-resistance’, and significantly reduce metabolically dormant persister cell populations. The literature search was performed using the electronic databases PubMed, Scopus, Web of Science, and Google Scholar. Publications indexed between 2015 and 2025 were primarily considered, while seminal studies published before 2015 were included when necessary to provide historical context and foundational knowledge. We place specific emphasis on next-generation biomimetic and exosome-inspired nanocarriers, which significantly reduce systemic host toxicity while maximizing targeted antifungal efficacy. In this context, the synergistic integration of smart nanocarriers to actively disassemble fungal resistance networks, such as the target of rapamycin (TOR) signaling pathway and sphingolipid biosynthesis. Finally, we outline a strategic roadmap to bridge the translational “Valley of Death”. By prioritizing manufacturing standardization, comprehensive long-term biosecurity profiling, and rationally designed biomimetic platforms, we propose an alternative way to outpace the evolutionary adaptations of fungal pathogenesis and translate these innovations into the clinic. Full article

Infectious diseases constitute a major public health concern and a leading cause of morbidity and mortality worldwide. The eye, by virtue of its rich vascularity and unique immunological microenvironment, is susceptible to involvement by a broad spectrum of bacterial, viral, fungal, and parasitic systemic infections, which may lead to diverse ocular and visual manifestations through direct pathogen invasion, immune-mediated mechanisms, or complications of therapy. Notable systemic infections with potential ocular involvement include tuberculosis; the spirochetal illnesses syphilis, Lyme disease, and leptospirosis; brucellosis; cat-scratch disease; leprosy; infective endocarditis; human immunodeficiency virus, cytomegalovirus, West Nile virus, and adenovirus infections; rubeola; dengue fever; candidiasis; cryptococcosis; aspergillosis; mucormycosis; toxoplasmosis; malaria; onchocerciasis; and cysticercosis. Ocular manifestations can serve as early diagnostic clues to underlying systemic infections, whereas, conversely, systemic features can help interpret ocular findings. Effective investigation and management of systemic infections benefit from a multidisciplinary approach, in which ophthalmologists can contribute substantially and help optimize both visual and overall health outcomes. Full article

Rhino-orbital mucormycosis is a rare, life-threatening opportunistic fungal infection, typically affecting immunocompromised patients. During the COVID-19 pandemic, increased cases were mainly linked to SARS-CoV-2 infection, diabetes, and corticosteroid exposure. We report a severe case in a previously healthy 44-year-old immunocompetent man who developed acute left-sided exophthalmos, ophthalmoplegia, severe visual loss, and systemic deterioration 10 days after AZD1222 COVID-19 vaccination. Clinical and radiologic findings suggested invasive rhino-orbital fungal disease, prompting immediate liposomal amphotericin B, broad-spectrum antibiotics, urgent endoscopic sinus surgery, and repeated orbital–sinonasal debridements with amphotericin B irrigation. Histopathological examination demonstrated broad aseptate hyphae with tissue necrosis, consistent with mucormycosis, while fungal culture and ITS sequencing identified Rhizopus arrhizus as the causative species. Therapy was later adjusted to include isavuconazole and antibacterial coverage for persistent inflammation and secondary colonization. Orbital and systemic improvement occurred within the first week, with globe preservation and marked proptosis reduction at 6 months, despite persistent ophthalmoplegia and residual light perception. Isavuconazole was continued for 2 years, with no recurrence during 3 years of follow-up. Although causality with vaccination cannot be established, the temporal association and biological plausibility warrant further investigation. Early suspicion and prompt combined medical–surgical management are essential in rapidly progressive orbital cellulitis. Full article

Introduction: Candidemia is the most significant invasive fungal disease in critically ill patients. As a shift towards non-albicans Candida (NAC) species has been observed in recent years, differentiation among Candida species is essential for appropriate therapeutic management and improved prognosis. This study evaluated trends in the epidemiology of candidemia, species-specific characteristics, treatment practices, and mortality in a multidisciplinary Greek intensive care unit (ICU). Materials and Methods: In this single-center retrospective observational study, 90 ICU patients with candidemia were evaluated. Clinical characteristics, infection-related factors, treatment practices, and outcomes were compared according to isolated Candida species and patient survival. Results: C. parapsilosis accounted for the majority of isolates (33.7%; 41.9% fluconazole-resistant), followed by C. albicans (31.5%) and Candidozyma auris (23.9%). No significant differences in co-morbidities, origin of candidemia, or treatment-related factors were identified. However, NAC bloodstream infections occurred significantly later during ICU hospitalization, were associated with lower disease severity, and were preceded by nearly five-fold higher exposure to antifungal agents before candidemia onset. Overall, the ICU mortality rate was 53.3%. No significant differences were observed among species-specific mortality rates. Neither prompt initiation of antifungal therapy nor the antifungal class administered was associated with improved survival. Conclusions: NAC species predominated among candidemia episodes in critically ill patients, with C. parapsilosis emerging as the most frequent isolate and exhibiting substantial fluconazole resistance. Mortality remained high and did not differ significantly according to species. Treatment timing and antifungal class were not associated with outcome, highlighting the need for continued surveillance and optimized management strategies in the ICU. Full article

Diagnostic failure in invasive fungal infections (IFIs) remains a relevant and underrecognized cause of mortality, morbidity, delayed therapy, unnecessary antifungal exposure, and pharmacological selective pressure. Although major advances have been achieved in biomarkers, rapid diagnostic tests, molecular methods, imaging studies, and microbiological identification, timely diagnosis continues to be influenced by the interaction among host factors, pathogen-related factors, diagnostic tools, and healthcare system–related factors. This narrative review analyzes diagnostic failure in IFIs as a dynamic process that includes delayed, incorrect, and incomplete diagnosis. It examines its determinants and consequences in high-risk populations—critically ill patients, patients with hematologic diseases or hematopoietic stem cell transplant recipients, and neonates—as well as in invasive candidiasis, aspergillosis, mucormycosis, cryptococcosis, endemic mycoses, and infections caused by rare or emerging fungi. It also reviews how delayed sampling, decontextualized interpretation of biomarkers, incomplete microbiological identification, absence of antifungal susceptibility testing when clinically relevant, and fragmentation between clinical and laboratory teams contribute to adverse outcomes. Finally, it proposes a diagnostic-centered antifungal stewardship framework (AFSP-Dx) based on syndromic bundles, population-specific diagnostic algorithms, 48–72 h reassessment, and auditable indicators intended to support earlier recognition, more precise therapeutic decisions, and rational antifungal use. Full article

Background: As hyperbaric oxygen therapy has been sporadically used in combination with antimicrobial treatment for refractory infections in patients with hematologic malignancies, data on its efficacy and outcomes are limited. Methods: We retrospectively analyzed 55 patients with hematologic malignancies treated with hyperbaric oxygen therapy over a 10-year period at a single tertiary care center and report on patients’ clinical features, infection types, treatment responses, and survival outcomes. Results: The most common underlying hematologic malignancy diagnosis was acute myeloid leukemia (30 patients, 55%). The most common hyperbaric oxygen therapy indications were invasive mold disease (IMD) (35 patients, 64%), BK virus-associated cystitis (17 patients, 31%), and bacterial cellulitis (3 patients, 5%). Patients underwent a median of 10 hyperbaric oxygen therapy sessions (range, 1–45). In total, 54 (98%) of the 55 patients were evaluable for response, of whom 32 (59%) patients demonstrated a response, defined as either resolution or stabilization of the infection. Among the 35 patients with IMDs, we found that 11 patients (31%) achieved a complete response, 5 (14%) had a partial response, 6 (17%) had stable disease, and 13 (37%) patients experienced progression of their infection. In contrast, among the 17 patients with BK virus-associated cystitis, 9 patients (53%) had persistent or worsening hematuria. The two evaluable patients with bacterial cellulitis responded with resolution of the infection. We reviewed the status of the hematologic malignancies at the time of hyperbaric oxygen therapy treatment and found that the 21 patients whose hematologic malignancies were in remission tended to have a higher response rate of their infection compared to patients whose hematologic malignancies were not in remission (73% vs. 46% p = 0.057). Despite the response of infections, 1-year mortality in these patients remained high at 76%. Conclusions: Based on our experience, hyperbaric oxygen therapy, in conjunction with appropriate anti-infective therapy and debridement surgery, could benefit selected patients with hematologic malignancies, especially those whose underlying disease is controlled but experience recalcitrant bacterial or fungal infections. Full article

Canker is a major fungal disease that causes substantial yield losses in pitaya (Selenicereus monacanthus (Lemaire) D.R.Hunt, syn. Hylocereus polyrhizus (F.A.C. Weber) Britton and Rose; red-fleshed pitaya). However, how fruit ripening and pathogenesis interactively shape fungal communities in fruit peels remains unclear. Here, we investigated the diversity, assembly mechanisms, co-occurrence networks, and functional guilds of fungal communities in healthy and diseased fruit peels at immature (green) and mature (red) stages of ‘Jindu No. 1’ pitaya using ITS1 amplicon sequencing. Our results revealed that fruit maturity exerted stronger effects on fungal community structure than disease status, with ripening reducing diversity and increasing dominance. Notably, disease-induced stage-dependent responses: immature communities shifted from stochastic to deterministic assembly under pathogen selection, whereas mature communities maintained stochastic processes despite infection. Co-occurrence network analysis revealed that healthy mature peels formed highly complex, cooperative networks with dense positive interactions, while healthy immature peels exhibited fragmented, modular structures vulnerable to invasion. Diseased immature peels displayed intermediate network topology, and diseased mature peels showed disrupted connectivity. Functionally, healthy fruits maintained balanced pathotroph-saprotroph-symbiotroph guilds, whereas diseased fruits exhibited higher relative abundance of pathotrophs and saprotrophs, reflecting a shift from symbiotic nutrient cycling toward necrotrophic pathogenicity and decomposition. These findings challenge the single-pathogen paradigm by revealing canker as an ecological process involving community-wide restructuring. They provide a theoretical basis for stage-specific microbiome-targeted disease management in tropical fruits, emphasizing the preservation of stochastic assembly and cooperative network structures to enhance disease resistance. Full article

Background: The coronavirus disease 2019 (COVID-19) pandemic coincided with substantial changes in healthcare delivery and antimicrobial resistance (AMR) patterns worldwide, particularly in intensive care units (ICUs), where invasive procedures and broad-spectrum antibiotics are commonly used. Data from Türkiye remains limited. Methods: This retrospective observational study evaluated bacterial and fungal isolates from adult ICU patients at a tertiary hospital from 2016 to 2025. Microorganisms were identified, and antimicrobial susceptibility testing was performed using standardized methods. Resistance patterns were compared between the pre-pandemic (January 2016–February 2020) and post-pandemic (March 2020–May 2025) periods. Results: A total of 2666 patients and 5433 isolates were analyzed. Gram-negative pathogens showed marked increases in resistance: carbapenem and colistin resistance in Klebsiella pneumoniae were significantly higher in the post-pandemic period (69.6% vs. 44.4% and 60.5% vs. 22.5%, respectively; p < 0.001). Resistance rates to multiple antimicrobial agents also increased in Acinetobacter baumannii and Pseudomonas aeruginosa (p < 0.05). Among Gram-positive bacteria, vancomycin-resistant Enterococcus faecium increased from 10% to 47.1%. Candida auris emerged only in the post-pandemic period, showing high resistance to fluconazole (75%) and amphotericin B (36.7%). Conclusions: Significant differences in AMR patterns were observed between the pre- and post-pandemic periods in this ICU population. Higher resistance rates were observed among several clinically important bacterial pathogens, and Candida auris emerged exclusively during the post-pandemic period. Given the study’s observational design, these findings should be interpreted as temporal associations rather than evidence of a causal effect of the COVID-19 pandemic. Continued antimicrobial stewardship and infection-control measures remain essential to address the growing burden of AMR. Full article