In Search of Alternative Antibiotic Drugs: Quorum-Quenching Activity in Sponges and their Bacterial Isolates

Abstract

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 example of this therapeutic concept 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 14 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 ≈20% of the isolates showed QQ activity based on a Chromobacterium violaceum CV026 screen, and that the presence or absence of QQ activity in a sponge extract did not correlate with the abundance of isolates with the same activity from the same sponge species. 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 bacterial Operational Taxonomic Units (OTUs) in a dataset including 97 sponge species and 178 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.

Quorum Sensing Inhibitors from the Sea Discovered Using Bacterial N-acyl-homoserine Lactone-Based Biosensors

“…These compounds were previously reported from I. felix based on their antimicrobial properties [94,95]. Similarly, Saurav et al [96] screened marine sponges from the Mediterranean and Red Sea for QSI activity using the QSIS1 biosensor and C. violaceum CV026 systems and observed, QSI as a common phenomenon within half of the sponge species tested. Four sponge species extracts were observed to inhibit QS activity; more precisely, two Red Sea sponges, Suberites clavatus and Negombata magnifica , and two Mediterranean Sea species, Ircinia variabilis and Sarcotragus sp.…”

Identification of Quorum Sensing Activators and Inhibitors in The Marine Sponge Sarcotragus spinosulus

“…The remaining part of all the five freeze-dried biomass specimens was macerated and repeatedly extracted with MeOH (0.5 L × 3), MeOH/CHCl 3 (0.5 L × 2), and CHCl 3 (0.5 L × 2) separately at room temperature. QSI activity was tested using biosensors Chromobacterium violaceum CV026 [58] and with an adaptation of the thin layer chromatography (TLC) overlay technique using Agrobacterium tumefaciens NT1 (pZLR4) [25,59]. In order to improve the detection ability of AHLs in sponge extracts, we combined all the five specimen extracts (7.8 g) and fractionated the combined extracts by reversed-phase flash column chromatography (Sigma ODS-A, 60 Å 500/400 mesh), eluting with a solvent system of 0 to 100% H 2 O/CH 3 CN and then with 100% MeOH, to afford sixteen fractions (FrS1-FrS16).…”

Plakofuranolactone as a Quorum Quenching Agent from the Indonesian Sponge Plakortis cf. lita

“…Because QS regulates virulence in pathogens like P. aeruginosa , interference with QS (quorum quenching, QQ) has been proposed as a potential therapeutic strategy for fighting pathogens by attenuating the virulence effectors that are regulated by QS [15]. QQ potential was detected in marine sponges and sponge isolates [16,17] and therefore sponges appear as an attractive target to identify novel anti-virulence and QS-inhibiting lead molecules. One means of QS-inactivation is to block the QS signal receptors (e.g., LasR in P. aeruginosa ) with the antagonist capable of penetrating the bacterial cell, and blocking the cascade of production of virulence factors.…”