Antibacterial Effects of Polycephalomyces nipponicus (Ascomycota) Mycelial Extract on Salmonella enterica Serovar Typhi.

The rise of antibiotic-resistant bacteria, particularly Salmonella enterica subsp. enterica serovar Typhi (S. Typhi), poses a significant challenge to global public health. This study investigates the antibacterial potential of mycelial extract from the medicinal fungus Polycephalomyces nipponicus strain Cod-MK1201 against S. Typhi strain DMST 16122. The extract demonstrated significant inhibitory effects, with minimum inhibitory concentration and minimum bactericidal concentration values of 3.12 mg/mL and 6.25 mg/mL, respectively. Scanning and transmission electron microscopy revealed dose-dependent severe morphological damage to S. Typhi cells, including cell wall disruption, cytoplasmic leakage, and structural deformation, indicating the extract's ability to target multiple cellular structures. Additionally, proteomic analysis showed significant alterations in the bacterial proteome, with downregulation of key proteins involved in metabolism, stress response, and virulence, and upregulation of proteins related to oxidative stress response and the stringent survival pathway. These findings demonstrate the multifaceted antimicrobial mechanisms of P. nipponicus mycelial extract, indicating its potential as a natural resource for developing novel therapeutic agents to treat S. Typhi infections. This highlights its promise as a candidate for reducing antibiotic dependency and addressing the growing challenge of antimicrobial resistance.