Formation of correct disulfide bonds in the endoplasmic reticulum is a crucial step for folding proteins destined for secretion. Protein disulfide isomerases (PDIs) play a central role in this process. We report a previously unidentified, hypervariable family of PDIs that represents the most diverse gene family of oxidoreductases described in a single genus to date. These enzymes are highly expressed specifically in the venom glands of predatory cone snails, animals that synthesize a remarkably diverse set of cysteine-rich peptide toxins (conotoxins). Enzymes in this PDI family, termed conotoxin-specific PDIs, significantly and differentially accelerate the kinetics of disulfide-bond formation of several conotoxins. Our results are consistent with a unique biological scenario associated with protein folding: The diversification of a family of foldases can be correlated with the rapid evolution of an unprecedented diversity of disulfide-rich structural domains expressed by venomous marine snails in the superfamily Conoidea.

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Fish support microbial communities that serve a variety of functions, including disease resistance. In addition to fish microbiota acting as a defense against disease, fish mucus often contains antimicrobial compounds. This study investigated the antibacterial activity of bacteria isolated from external surfaces of native (e.g. Indo-Pacific) and invasive (e.g. Western Atlantic, Caribbean) lionfish (Pterois volitans/miles complex) and native Caribbean squirrelfish Holocentrus adscensionis against 6 known fish pathogens (Vibrio spp., Photobacterium damselae), and evaluated the antibacterial activity of lionfish mucus against these pathogens and lionfishand squirrelfish-associated bacteria. The 16S rRNA gene was sequenced for bacteria exhibiting pathogen inhibition, providing information on their taxonomic affiliations. Antibacterial metabolites were produced by 36.2% (54 of 149) of lionfish-derived bacterial cultures, with similar percentages of producing organisms recovered from the native and invaded ranges. Only 1 of 13 squirrelfish isolates inhibited pathogens. Interestingly, similar genera exhibiting antibacterial activity were detected in both ranges (e.g. Alteromonas, Pseudoalteromonas, Photobacterium), even though previous work suggested that external bacterial communities were not vertically transmitted. Antibacterial activity was detected after 24 h of growth, and the amount of inhibition did not increase over a 14 d incubation period. Conversely, organic and aqueous mucus extracts from lionfish were not active against the 6 pathogens or against bacteria isolated from lionfish and squirrelfish. These findings indicate that the external bacterial communities of lionfish may provide disease resistance to their hosts, a trait that would enhance the ability of lionfish to successfully establish as an invasive species.