Jinhan Yu

Fusarium solani (F. solani) is a rare cause of endophthalmitis, most commonly occurring after ocular trauma, surgery, or in immunocompromised individuals. Fungal endophthalmitis carries a distinctly poor prognosis. Among published cases of Fusarium endophthalmitis, enucleation rates exceed 20%. Mortality in disseminated infections among immunocompromised hosts approaches 50–80%, reaching nearly 100% in persistently neutropenic patients. Even among patients who retain the eye, significant visual impairment is nearly universal. To our knowledge, cases arising spontaneously in immunocompetent individuals without any identifiable risk factors have not been previously documented. We report a case of endophthalmitis in an otherwise healthy woman with no apparent risk factors. Initial conventional cultures of ocular samples yielded negative results. However, F. solani was ultimately identified through three consecutive next-generation sequencing (NGS) analyses and by inoculating aqueous humor into blood culture bottles. The patient was treated with vitrectomy, intravitreal injection of amphotericin B and oral voriconazole. Despite aggressive antifungal therapy, the infection progressed rapidly, ultimately necessitating evisceration of the affected eye. We report a case of endophthalmitis in a 67-year-old immunocompetent woman with no history of ocular breach or systemic immunosuppression. Initial conventional cultures of aqueous humor were negative. The pathogen was ultimately identified through repeated NGS and by inoculating aqueous humor into blood culture bottles. The isolate was confirmed as Fusarium solani by ITS and TEF-1α sequencing. Antifungal susceptibility testing showed MICs of 1 μg/mL for both amphotericin B and voriconazole, values well within the wild-type range. Despite guideline-adherent combination therapy (amphotericin B and voriconazole) and early vitrectomy, the infection progressed relentlessly and ultimately necessitating evisceration. To our knowledge, this represents the first documented case of F. solani endophthalmitis occurring in the absence of identifiable risk factors in an immunocompetent host. This case underscores the diagnostic value of NGS in detecting rare ocular pathogens, and the potential utility of blood culture bottle inoculation for pathogen recovery. Besides, this case report also reminds us that in vitro antifungal susceptibility does not guarantee in vivo efficacy in Fusarium endophthalmitis. It also highlights the importance of considering filamentous fungi in the differential diagnosis of unexplained intraocular infections, even in patients without classical risk factors.

Candida krusei is an opportunistic pathogen with intrinsic resistance to fluconazole. This study analyzed 174 C . krusei isolates from bloodstream infections (BSI, n = 115) and non-blood sources ( n = 59). Biochemical profiling using the VITEK 2 YST ID Card revealed a significant difference in the TyrA reaction between BSI and non-blood isolates ( P < 0.05). Antifungal susceptibility testing via CLSI broth microdilution and Sensititre YeastOne showed that BSI isolates were more susceptible to echinocandins and azoles than non-blood strains, with minor MIC discrepancies between methods. Microsatellite genotyping at eight loci demonstrated high genetic diversity. Notably, a cluster of respiratory isolates from COVID-19 patients suggested potential nosocomial transmission. The integration of phenotypic, susceptibility, and genotypic data highlights possible virulence traits and epidemiological patterns. These findings may support the development of tailored antifungal therapies and improved infection control, particularly for high-risk populations such as ICU and COVID-19 patients. IMPORTANCE: Bloodstream infections caused by C. krusei are associated with high mortality rates and limited therapeutic options, emphasizing the need to better understand the factors contributing to its pathogenicity and invasive potential. This study provides critical insights into the biology and clinical impact of C. krusei . By integrating biochemical, antifungal susceptibility, and genotypic analyses of bloodstream and non-bloodstream isolates, it reveals distinct phenotypic and resistance profiles, high genetic diversity, and potential nosocomial transmission in COVID-19 patients. These findings underscore the importance of recognizing population-specific traits in C. krusei , which may guide tailored antifungal strategies and strengthen infection control measures, especially for vulnerable groups such as ICU and immunocompromised patients.

Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis of early childhood and remains the leading cause of acquired heart disease in developed nations. Despite decades of investigation, its etiology and immunopathogenesis are still not fully understood. This review integrates nearly six decades of histopathological, epidemiological, and immunological research to examine infection-driven mechanisms underlying KD. Current evidence indicates that KD may result from a convergence of microbial and host factors: viral infections can trigger mucosal IgA-mediated immune activation; superantigens may induce T-cell receptor (TCR) Vβ–skewed cytokine release; conventional antigens appear to elicit oligoclonal adaptive immune responses consistent with infection-associated vasculitis; and gut microbiota dysbiosis may amplify systemic inflammation through disruption of intestinal barrier integrity and short-chain fatty acid metabolism. Rather than a single-pathogen infection, KD likely reflects infection-triggered immune dysregulation in genetically susceptible children. By contrasting these mechanistic hypotheses, this review highlights the need for longitudinal, multi-omics studies integrating metagenomic, transcriptomic, and serologic analyses to delineate causal microbial signatures, identify diagnostic biomarkers, and guide precision immunomodulatory strategies for this complex pediatric vasculitis.

Invasive fungal infections pose a significant health threat. Yarrowia lipolytica (formerly known as Candida lipolytica) is an opportunistic yeast with pathogenic potential, but its virulence and impact on the host remain poorly understood. This study aimed to investigate the infection characteristics associated with this relatively unknown pathogen by establishing reliable animal models. We developed intravenous challenge models in immunocompetent and immunosuppressed BALB/c mice by injecting fungal cells directly into the bloodstream. In immunocompetent mice, Y. lipolytica was effectively cleared even at the highest challenge dose of 1 × 10⁸ cells, resulting in minimal mortality. However, this clearance was accompanied by a significant elevation in peripheral blood cytokine levels. Three days post-infection, the fungal burden was highest in the lungs (P < 0.0001), followed by the spleen, kidneys, liver, and brain. In immunosuppressed mice, the mortality rate following Y. lipolytica infection significantly increased (P < 0.001), with the highest fungal burden consistently observed in the lungs. In the immunosuppressed model, clinical isolates exhibited a greater lung fungal burden compared to industrial isolate. In conclusion, Y. lipolytica is a low-virulence fungus that is challenging to establish as a fatal infection in immunocompetent hosts but exhibits a marked tropism for the lungs, where lung fungal burden serves as an effective indicator of virulence. This model may also provide critical insights for studying fungal pulmonary infection pathogenesis and the infection dynamics of Y. lipolytica, especially for immunocompromised patients.

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)–producing MAIT1 and interleukin-17A (IL-17A)–producing MAIT17 cell subsets in vivo. Whereas T-bet ⁺ MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt ⁺ MAIT17 cells could undergo phenotypic and functional conversion into both RORγt ⁺ T-bet ⁺ MAIT1/17 and RORγt ⁻ T-bet ⁺ MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A–secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell–targeted vaccines.

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.

Moraxella catarrhalis, a commensal in the human nasopharynx, plays a significant role in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Its pathogenicity involves adherence to respiratory epithelial cells, leading to infection through a macropinocytosis-like mechanism. Previous investigations highlighted the diverse abilities of M. catarrhalis isolates with different phenotypes to adhere to and invade respiratory epithelial cells. This study used a murine COPD model and in vitro experiments to explore the factors influencing the pathogenicity of distinct phenotypes of M. catarrhalis. Transcriptome sequencing suggested a potential association between actin cytoskeleton regulation and the infection of lung epithelial cells by M. catarrhalis with different phenotypes. Electron microscopy and Western blot analyses revealed a decrease in filamentous actin (F-actin) expression upon infection with various M. catarrhalis phenotypes. Inhibition of actin polymerization indicated the involvement of F-actin dynamics in M. catarrhalis internalization, distinguishing it from the adhesion process. Notably, hindering F-actin polymerization impaired the internalization of M. catarrhalis. These findings contribute vital theoretical insights for developing preventive strategies and individualized clinical treatments for AECOPD patients infected with M. catarrhalis. The study underscores the importance of understanding the nuanced interactions between M. catarrhalis phenotypes and host lung epithelial cells, offering valuable implications for the management of AECOPD infections.

The antifungal susceptibility profile and epidemiological cut-off values (ECOFFs) of Yarrowia lipolytica , a rare opportunistic yeast, remain unclear. We conducted a comprehensive multi-method study on clinical isolates from various central hospitals, based on the China Hospital Invasive Fungal Surveillance Network (2009–2022). Our objective was to evaluate the antifungal susceptibility of Y. lipolytica , establish its local ECOFFs (L-ECOFFs), and compare the performance of the ATB FUNGUS 3 (ATB), Sensititre YeastOne (SYO), and minimum inhibitory concentration (MIC) test strip (MTS) with that of the broth microdilution (BMD) method. L-ECOFFs were established using ECOFFinder, and we examined ERG11 mutations to assess the reliability of the L-ECOFFs. The L-ECOFF for fluconazole was 8 µg/mL. Non-wild-type isolates of antifungal drugs, such as flucytosine and azoles, were exclusively isolated from patients. Additionally, we detected that four strains with the ERG11 A395T mutation (azole MIC >L-ECOFF) may be associated with the exposure to azole drugs. For azoles, ATB showed the highest essential agreement with the BMD (98.18%–100%), followed by SYO (85.45%–100%). However, ATB could not detect susceptibility to echinocandins, while SYO exhibited the highest agreement (98.18%–100%) in detecting echinocandin susceptibility. Our findings indicate that acquired azole cross-resistance has emerged despite Y. lipolytica infections being rare. This research provides crucial antifungal susceptibility data and establishes the initial L-ECOFFs for Y. lipolytica . The SYO is recommended as the optimal laboratory antifungal susceptibility testing method for Y. lipolytica , followed by ATB, whereas the use of MTS requires caution. We hope that this study will facilitate improved clinical management of Y. lipolytica infections. IMPORTANCE: Yarrowia lipolytica , also known as Candida lipolytica , is an emerging opportunistic “rare pathogenic yeast”. Due to the limited data on its antifungal susceptibility, the clinical treatments become challenging. Based on the China Hospital Invasive Fungal Surveillance Network (2009–2022), we conducted a comprehensive multi-method study on clinical isolates from various central hospitals. This study is currently the largest study carried out to assess the antifungal susceptibility of Y. lipolytica . It is also the first to establish local epidemiological cut-off values (L-ECOFFs), identify its ERG11 mutations, and assess the consistency between the three prevalent commercial antifungal susceptibility testing methods and the broth microdilution method. We recommend the Sensititre YeastOne as the best option for antifungal susceptibility testing for Y. lipolytica , followed by the ATB FUNGUS 3. Nevertheless, practitioners should use the MIC test strip with discretion.

Serological testing (immunoassay) for Helicobacter pylori (H. pylori) is widely available and inexpensive, and does not require medication modifications before testing. It can also determine the type of infection, which helps with clinical diagnosis and treatment, and guides the use of medication. However, the performance of immunoblotting for the detection of H. pylori infections in different populations has still not been fully evaluated. We performed a retrospective analysis of patients in the Health Examination Center and Outpatient Department, from November 2017 to September 2020, at Peking Union Medical College Hospital. All the subjects were tested with the ¹³C-urea breath test (¹³C-UBT) and for IgG antibodies. A total of 1678 participants, including 1377 individuals who had undergone physical examinations, were recruited. The results of the immunoassay were significantly different from those of the ¹³C-UBT for all the subjects and outpatients (p < 0.001). For the physical examinations of individuals, the agreement between the immunoassay and the ¹³C-UBT was 0.64 (95%CI: 0.59–0.68; p < 0.001), and the H. pylori immunoassay demonstrated a sensitivity and specificity of 74.24% and 90.45%, respectively, with a positive predictive value of 71.01% and negative predictive value of 91.76%. In addition, in patients with gastric mucosal atrophy or early gastric cancer, antibody typing tests can also detect infected patients with missed UBT. The prevalence of H. pylori in Beijing was 26.8%, and the serological positivity rate for H. pylori in the population of Beijing was about 31.7% (25.1% in the physical examination population). The rate of H. pylori antibody positivity among patients with allergic diseases was 73.5%, which is significantly higher than that of the non-allergic disease population (29.3%, p < 0.001). In conclusion, H. pylori antibody typing testing can be applied as a specific test in the healthy physical examination population, and the test can be performed with the remaining serum during the physical examination.