Invasive fungal diseases remain a major unresolved challenge in the field of infectious diseases, driven by the interplay of limited therapeutic options, the rapid emergence and global spread of antifungal-resistant strains, and the persistent difficulty of achieving rapid and accurate diagnosis. In recent years, the increasing prevalence of antifungal-resistant fungi has become particularly evident worldwide, resulting in a growing number of cases in which currently available therapies fail to provide sufficient clinical efficacy. In response to this alarming situation, the World Health Organization (WHO) released the Fungal Priority Pathogens List (FPPL) in 2022, formally identifying priority fungal pathogens and designating enhanced surveillance, the development of novel therapeutic strategies, and the advancement of diagnostic technologies as urgent international priorities. This initiative has underscored the pressing need for rapid and innovative countermeasures against fungal diseases on a global scale. Despite these efforts, the antifungal agents currently available for clinical use remain limited in both number and diversity of mechanisms of action. Most existing drugs target a narrow range of fungal-specific structures or pathways, such as ergosterol or cell wall biosynthesis, and are frequently associated with significant adverse effects and toxicity. As a result, therapeutic innovation in the field of mycoses has stagnated for decades, further exacerbating the clinical burden posed by resistant and refractory infections. Against this backdrop, this review focuses on a novel strategy aimed at overcoming these challenges: a fungus-targeted drug delivery system developed by our group. We discuss its conceptual framework, design principles, and therapeutic potential, and further explore its application as a platform technology for nucleic acid-based therapeutics. In particular, we highlight the prospective utility of microRNA-mediated control of fungal pathogenicity as an emerging strategy for nucleic acid-based antifungal therapy, thereby providing a promising platform for next-generation antifungal therapeutics.

Antiviral immune responses induced by probiotics are known to involve microbial metabolites that stimulate macrophages to produce type I interferons (IFNs). However, due to the limited capacity of macrophages to produce IFNs, the robust production of IFN-α by plasmacytoid dendritic cells (pDCs) plays a crucial role in antiviral host defense. This study investigated whether live probiotic bacteria isolated from commercial products can directly stimulate pDCs to induce IFN-α production.

Five live bacterial strains cultured from commercial yogurts and supplements were evaluated: Lactococcus lactis strain Plasma, Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1, Bifidobacterium longum subsp. longum BB536, Lactobacillus gasseri SBT2055, and Lacticaseibacillus rhamnosus CRL1505. Mouse-derived pDCs were co-cultured with these strains. Cellular internalization was assessed using confocal laser scanning microscopy, and IFN-α production was measured by ELISA.

Only L. lactis strain Plasma was localized within the intracellular compartments of pDCs and induced significant IFN-α production (12.6±3.3 pg/mL). In contrast, the other four probiotic strains showed no evidence of cellular internalization, and IFN-α production remained below the detection limit.

These findings suggest that the activation of pDCs by live probiotic bacteria is strictly strain-specific. L. lactis strain Plasma, which specifically translocates into pDCs and activates the Toll-like receptor 9 (TLR9) pathway, may represent a promising strategy for the prevention of various viral infections, including COVID-19, as well as for the enhancement of antiviral immunity.

Linezolid (LZD) is increasingly used for multidrug-resistant tuberculosis (MDR-TB) and nontuberculous mycobacteria (NTM) infections; however, peripheral neuropathy and optic nerve disorders are important adverse events associated with prolonged treatment. This study evaluated disproportionality signals for LZD-associated neuropathy using the Japanese Adverse Drug Event Report (JADER) database. The JADER reports submitted between April 2004 and November 2025 were analyzed. Tuberculosis- and NTM-related cases were extracted using disease-related keywords. Reports involving LZD were classified into the LZD group, whereas the remaining reports were classified into the non-LZD group. Reporting odds ratios (RORs), 95% confidence intervals (CIs), and Fisher’s exact tests were calculated for optic nerve disorders and peripheral neuropathy using standardized Medical Dictionary for Regulatory Activities queries. Sensitivity analyses according to concomitant ethambutol or isoniazid use and time-to-onset (TTO) analyses were also performed. After excluding duplicate reports, 250 LZD-related and 4,807 non-LZD-related cases were analyzed. Significant disproportionality signals were detected for optic nerve disorders (ROR, 3.67, 95% CI: 2.29–5.90, p < 0.001) and peripheral neuropathy (ROR, 20.48, 95% CI: 12.31–34.05, p < 0.001) in the LZD group. Elevated signals remained in analyses excluding concomitant ethambutol or isoniazid use. Median TTOs for peripheral neuropathy and optic nerve disorders were 98 days [interquartile range (IQR), 96.5–188 days] and 272 days (IQR, 173–404 days), respectively. LZD was associated with elevated reporting signals for optic nerve disorders and peripheral neuropathy in tuberculosis- and NTM-related reports. Prolonged neurological monitoring may be important during long-term LZD treatment.