An international research team involving the Institute of Integrative Systems Biology (I2SysBio, CSIC-UV), located at the University of Valencia Science Park , has just published in the journal Microbiome a study that reveals the presence of betalactones, a group of little-studied substances with pharmaceutical potential generated by symbiotic bacteria that inhabit the skin of a species of nudibranch, a sea slug. This is the first time that a compound of pharmacological interest has been found in this group of mollusks, using an innovative technique that promises to expand the knowledge of this type of substances of bacterial origin.
Nudibranchs comprise a group of more than 6,000 species of soft-bodied marine mollusks known as "sea slugs." They use secondary metabolites (natural substances) for chemical defense, but the full diversity of these substances remains unexplored, so their potential therapeutic applications are unknown.
Scientists often search for genes encoding natural products of pharmacological interest in the genomes of uncultured microbes using computational tools, but there is no guarantee that the genes detected are functional. During her postdoc in the United States at Lawrence Berkeley National Laboratory, Mária Džunková used a fluorescent probe developed at the University of California, San Diego, to tag bacteria that produce natural products.
Nudibranchs comprise a group of more than 6,000 species of soft-bodied marine mollusks known as "sea slugs". They use secondary metabolites (natural substances) for chemical defense, but the full diversity of these substances remains unexplored, so their potential therapeutic applications are unknown
Džunková, who is a researcher at the University of Valencia's Institute of Integrative Systems Biology (I2SysBio, CSIC-UV), has explored the microbes inhabiting the nudibranch Doriopsilla fulva using fluorescence-activated cell sorting (FACS) and genomics of individual microbial cells. With this technique, bacteria that have taken up the fluorescent probe are collected and the DNA present in single cells is amplified. This allows obtaining sufficient quantities for the sequencing of the complete genome of each separate cell, allowing the identification of new bacterial species without the need to cultivate them in the laboratory.
With this new technique he discovered the presence of the unculturable bacterium Candidatus Doriopsillibacter californiensis, which belongs to an order of unculturable bacteria. "This bacterium has genes for the production of betalactones, a little-explored molecular group with pharmaceutical potential that has not been detected in nudibranchs before," says the researcher. "Future research will reveal whether it is possible to use this compound to treat diseases such as cancer or infections caused by viruses or bacteria," says Džunková.
According to the Slovakian researcher, who joined I2SysBio in 2021 to create its microbial single cell genomics research group, "this is the first study to document a natural product from symbiotic microbes inhabiting the skin of nudibranchs."
"This bacterium has genes for the production of betalactones, a little-explored molecular group with pharmaceutical potential that has not been detected in nudibranchs before," Mária Džunková, researcher at the University of Valencia's Institute of Integrative Systems Biology, said
Analyze other species of nudibranchs in Spain
His team analyzed the microbial composition of several individuals of the nudibranch Doriopsilla fulva, found off the coast of San Francisco (California, USA), and confirmed that the bacterium Candidatus Doriopsillibacter californiensis is the most important member of the microbial community of its skin. Extracts from this nudibranch contained natural products consistent with the betalactone found in its symbiotic bacteria.
Since this is a non-culturable bacterium, the Lawrence Berkeley National Laboratory team has used a new synthetic biology method called CRAGE (Chassis-independent Recombinase-Assisted Genome Engineering) developed in this laboratory, and are attempting to recover the complete molecule. Meanwhile, the I2SysBio team is analyzing other nudibranch species in Spain (Galicia, Basque Country, Andalusia and the Balearic Islands) in an attempt to discover more bacteria producing molecules of pharmaceutical interest.
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