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A broad variety of natural parabens, including four novel structures and known ethyl and butyl parabens, were obtained from culture of aMicrobulbifersp. bacterial strain isolated from the temperate calcareous marine spongeLeuconia nivea(Grant 1826). Their structures were elucidated from spectral analysis, including mass spectrometry and 1D and 2D nuclear magnetic resonance. Their antimicrobial activity evaluated againstStaphylococcus aureuswas characterized by much higherin vitroactivity of these natural paraben compounds 3-9 than commercial synthetic methyl and propyl parabens, usually used as antimicrobial preservatives. Compounds 4 and 9 revealed a bacteriostatic effect and compounds 6 and 7 appeared as bactericidal compounds. Major paraben compound 6 was also active against Gram positiveBacillussp. andPlanococcussp. sponge isolates and was detected in whole sponge extracts during all seasons, showing its persistentin situproduction within the sponge. Moreover,Microbulbifersp. bacteria were visualized in the sponge body wall using fluorescencein situhybridization with a probe specific to L4-n2 phylotypes. Co-detection in the sponge host of both paraben metabolites andMicrobulbifersp. L4-n2 indicates, for the first time, production of natural parabens in a sponge host, which may have an ecological role as chemical mediators.