Bacterial metabolites as larvicidal agents against Aedes aegypti: A systematic review and meta-analysis

The control of Aedes aegypti, the principal vector of arboviruses such as dengue, chikungunya, and Zika, remains a major public health challenge, largely due to the widespread resistance to chemical insecticides. In this context, bacterial extracts or their metabolites have emerged as promising alternatives for vector control. We conducted a systematic review following PRISMA guidelines, searching PubMed, Scopus, and Web of Science up to July 2025. Eligible studies reported the larvicidal activity of bacterial extracts, fractions, or purified compounds against Ae. aegypti larvae, including outcomes such as mortality, LC₅₀/LC₉₀ values, and sublethal effects. From an initial total of 1,023 records, 70 studies met the eligibility criteria and were included. The most frequently investigated genera were Bacillus and Lysinibacillus, with Cry and Bin toxins exhibiting LC₅₀ values in the ng/mL range, reinforcing their status as reference larvicides. Actinobacteria produced structurally diverse metabolites, including pelgipeptins, prodigiosin, and fabclavine, with larvicidal activity. Reported sublethal effects included inhibition of acetylcholinesterase activity and reduced larval development. A total of 45 studies met the criteria for quantitative synthesis; among these, 68% evaluated spore-protein complexes and 32% evaluated other bacterial material. LC₅₀ values ranged from 0.00048 to 126.56 µg/mL. Despite the overall promising activity observed, substantial methodological heterogeneity and the frequent absence of standardized positive and negative controls limited cross-study comparability. Bacterial metabolites remain strong candidates for the development of novel larvicidal agents; however, further progress toward field application will depend on standardized bioassays, robust chemical characterization, and ecological validation under realistic environmental conditions.