QUORUM-QUENCHING BASED ANTI-VIRULENCE POTENTIAL IN SPONGES AND THEIR BACTERIAL ISOLATES

Saurav Kumar 1 Rinat Bar-Shalom 1 Markus Haber 1 Ilia Burgsdorf 1 Giorgia Oliviero 2 Valeria Constantino 2 David Morgenstern 3 Laura Steindler 1
1Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Haifa, Israel
2The Blue Chemistry Lab Group, Department of Pharmacy, Università degli Studi di Napoli Federico II, Naples, Italy
3Bioinformatics Service Unit, University of Haifa, Haifa, Israel

Owing to the extensive development of drug resistance in pathogens against the available antibiotic arsenal, antimicrobial resistance is now an emerging major threat to public healthcare. Anti-virulence drugs are a new type of therapeutic agent aiming at virulence factors rather than killing the pathogen, thus providing less selective pressure for evolution of resistance. One promising such therapy targets bacterial quorum sensing (QS), because QS controls many virulence factors responsible for bacterial infections. Marine sponges and their associated bacteria are considered a still untapped source for unique chemical leads with a wide range of biological activities. In the present study, we screened extracts of fourteen sponge species collected from the Red and Mediterranean Sea for their quorum-quenching (QQ) potential. Half of the species showed QQ activity in at least 2 out of 3 replicates. Six out of the 14 species were selected for bacteria isolation, to test for QQ activity also in isolates, which, once cultured, represent an unlimited source of compounds. We show that approximately 20% of the isolates showed QQ activity, and that the presence or absence of QQ activity in a sponge extract could not predict the abundance of isolates with the same activity. This can be explained by the unknown source of QQ compounds in sponge-holobionts (host or symbionts), and further by the possible non-symbiotic nature of bacteria isolated from sponges. The potential symbiotic nature of the isolates showing QQ activity was tested according to the distribution and abundance of taxonomically close OTUs in a dataset including 97 sponge species and 181 environmental samples (i.e., seawater, freshwater and marine sediments). Most isolates were found not to be enriched in sponges, and may simply have been trapped in the filtration channels of the sponge at the time of collection. Our results highlight potential for QQ-bioactive lead molecules for anti-virulence therapy both from sponges and the bacteria isolated thereof, independently on the symbiotic nature of the latter.









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