Asian Journal of Microbiology and Biotechnology

The rising threat of antibiotic-resistant bacterial infections—commonly termed “superbugs”—necessitates the exploration of alternative therapeutic strategies. One promising approach lies in the utilization of antimicrobial proteins (AMPs) derived from oysters. These naturally occurring molecules, integral to the oyster’s innate immune system, exhibit potent antimicrobial activities through mechanisms such as membrane disruption, biofilm inhibition, and immunomodulation. Notably, proteins like big defensins (e.g., Cg-BigDef1 and Cg-BigDef5), histone-derived peptides, and other hemolymph proteins have demonstrated strong efficacy against multidrug-resistant (MDR) pathogens, including Streptococcus pneumoniae and S. pyogenes. Proteomic studies have identified several active constituents, such as cystatin B–like proteins and carbonic anhydrases, responsible for the bactericidal effects. Moreover, these proteins exhibit synergistic effects when combined with conventional antibiotics, thereby enhancing therapeutic outcomes and reducing resistance development. In addition to medical applications, oyster-derived AMPs show potential for use in agriculture and the food industry, particularly for biofilm control, food preservation, and reducing antibiotic reliance in livestock. Despite these advances, challenges such as peptide stability, large-scale production, and immunogenicity must be addressed before clinical implementation. This review highlights the current research, effectiveness, and potential applications of oyster antimicrobial proteins, proposing them as a promising frontier in combating superbug-related infections. Future research should therefore focus not only on therapeutic applications but also on overcoming these limitations to facilitate successful translation into clinical and industrial settings.