Protozoa: The Overlooked Frontiers of Natural Antimicrobial Compounds

Antimicrobial resistance (AMR) is becoming a major problem in the treatment of infectious diseases, increasing the need for new antimicrobial agents. Although bacteria and fungi have been extensively explored in antimicrobial discovery, protozoa remain comparatively underexplored despite their biological diversity and metabolic capabilities. Recent studies have reported that several protozoan species, including Acanthamoeba, Dictyostelium, Naegleria, and Entamoeba, are capable of exhibiting antimicrobial activity, particularly against multidrug-resistant (MDR) bacteria and fungi. These activities have been associated with a range of bioactive molecules, such as pore-forming peptides, proteases, and secondary metabolites produced by protozoa. The reported antimicrobial effects involve multiple mechanisms, including disruption of membrane integrity, induction of oxidative stress, and inhibition of biofilm formation. Despite these observations, research on protozoa-derived antimicrobial compounds remains limited due to challenges related to molecular characterization, large-scale cultivation, and the availability of in vivo data. This review summarizes current knowledge on bioactive molecules produced by protozoa, with emphasis on their ecological origins, mechanisms of action, and potential relevance to antimicrobial drug discovery. These findings suggest that protozoa-derived bioactive compounds may contribute to the ongoing search for novel and natural antimicrobial agents and may represent a promising complementary resource in efforts to combat antimicrobial resistance.