Bioactive Compounds Isolated from a Marine Sponge Selectively Inhibit Neisseria gonorrhoeae

Abstract

Background/objectives: Neisseria gonorrhoeae is the third most common sexually transmitted infection (STI), which may become untreatable soon if resistance continues to drastically increase. Due to increases in resistance to recommended antibiotics, alternative sources of novel compounds to combat this threat are being explored. Interestingly, marine sponges have proven to produce a plethora of bioactive compounds that display anticancer, antiviral, antifungal, and antibacterial activity.

Methods: In this study, the extracts of the sponge collected from Saint Thomas, US Virgin Islands were examined to determine their antibacterial activity against E. coli, S. aureus, and N. gonorrhoeae.

Results: The ethyl acetate sponge extracts significantly inhibited growth of N. gonorrhoeae, while none inhibited S. aureus and E. coli. The bioassay-guided purification of the ethyl acetate extract resulted in the isolation of 6-desmethyl-6-ethylspongosoritin A (1) and plakortone B (2). To determine if the pure sponge metabolite could improve the efficacy of ceftriaxone against a high-level ceftriaxone (HTX)-resistant gonococcal strain, an antibiotic checkerboard assay was done by combining various concentrations of either precursor fractions or the purified compound 2 with ceftriaxone. Plakortone B (2) and ceftriaxone acted in synergy against gonococcal strains and inhibited growth by increasing membrane permeability when exposed for 4 h and 24 h.

Conclusions: This suggests that marine sponges may serve as a source for novel bioactive compounds against antibiotic-resistant strains of N. gonorrhoeae, as well as improve the efficacy of currently prescribed antibiotics.

Keywords: antibiotic; bioactive; ceftriaxone; high-level ceftriaxone resistant; metabolite; minimal inhibitory concentration; natural products; sexually transmitted infections.

Figure 1

The compound BH5 isolated from a marine sponge increases membrane permeability of the FA19 wildtype. P values were determined via one-way ANOVA and are represented via asterisks to indicate levels of significance: (*) p < 0.05; (**) p < 0.01. The standard error of the mean (SEM) was determined based on assays using four independent biological samples.

Figure 2

Structures of (A) 6-desmethyl-6-ethylspongosoritin A (1) and (B) plakortone B (2).

Figure 3

Compound AH5_P2 isolated from a marine sponge extract AH5 increases the membrane permeability of the FA19 wildtype. P values represented via asterisks indicate levels of significance: (*) p < 0.05; (**) p < 0.01. The standard error of the mean (SEM) was determined based on assays using four independent biological samples.

Figure 4

Compound AH5_P2 increases the membrane permeability of strain HTX-41. P values represented via asterisks indicate levels of significance: (*) p < 0.05; (**) p < 0.01. The standard error of the mean (SEM) was determined based on assays using three independent biological samples.