Bis-Indole Alkaloids Isolated from the Sponge Spongosorites calcicola Disrupt Cell Membranes of MRSA

Abstract

Antimicrobial resistance (AMR) is a global health challenge with methicillin resistant Staphylococcus aureus (MRSA), a leading cause of nosocomial infection. In the search for novel antibiotics, marine sponges have become model organisms as they produce diverse bioactive compounds. We investigated and compared the antibacterial potential of 3 bis-indole alkaloids—bromodeoxytopsentin, bromotopsentin and spongotine A—isolated from the Northeastern Atlantic sponge Spongosorites calcicola. Antimicrobial activity was determined by MIC and time-kill assays. The mechanism of action of bis-indoles was assessed using bacterial cytological profiling via fluorescence microscopy. Finally, we investigated the ability of bis-indole alkaloids to decrease the cytotoxicity of pathogens upon co-incubation with HeLa cells through the measurement of mammalian cell lysis. The bis-indoles were bactericidal to clinically relevant Gram-positive pathogens including MRSA and to the Gram-negative gastroenteric pathogen Vibrio parahaemolyticus. Furthermore, the alkaloids were synergistic in combination with conventional antibiotics. Antimicrobial activity of the bis-indole alkaloids was due to rapid disruption and permeabilization of the bacterial cell membrane. Significantly, the bis-indoles reduced pathogen cytotoxicity toward mammalian cells, indicating their ability to prevent bacterial virulence. In conclusion, sponge bis-indole alkaloids are membrane-permeabilizing agents that represent good antibiotic candidates because of their potency against Gram-positive and Gram-negative bacterial pathogens.

Phenylpropane biosynthesis and alkaloid metabolism pathways involved in resistance of Amorphophallus spp. against soft rot disease

“…The effects of alkaloids on propagates of Pcc were additionally examined. The Pcc propagation experiment was performed according to the methods of reported by Khan et al ( Khan et al., 2022 ). and Ramkissoon et al ( Ramkissoon et al., 2020 ), with minor modifications.…”

Inhibition of bacterial biofilms by the snake venom proteome

“…The effect of N. samarensis venom on bacterial viability was assessed by time-kill assays against MRSA and MSSA [34] . 200 μL overnight bacterial culture (adjusted to 0.02 OD 595 ) was incubated in the presence and absence of 3.75 mg/mL N. samarensis venom in BHI for 24 h at 37 °C.…”

The Antitubercular Activities of Natural Products with Fused-Nitrogen-Containing Heterocycles

“…These are more complex structures as compared to their corresponding monomeric units and the bisindole is produced at a late stage in the biosynthetic process. These alkaloids exhibit diverse pharmacological properties including anticancer, antimalarial, antileishmanial, antibacterial and antimycobacterial activities [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. Staurosporine ( 9 , Figure 2 ) having the indolocarbazole core was originally isolated from Streptomyces staurosporeus AM-2282 T obtained from soil samples collected in Japan in 1977 [ 58 ].…”