Marine biomimetics: bromotyrosines loaded chitinous skeleton as source of antibacterial agents

Abstract

The marine sponges of the order Verongiida (Demospongiae: Porifera) have survived on our planet for more than 500 million years due to the presence of a unique strategy of chemical protection by biosynthesis of more than 300 derivatives of biologically active bromotyrosines as secondary metabolites. These compounds are synthesized within spherulocytes, highly specialized cells located within chitinous skeletal fibers of these sponges from where they can be extruded in the sea water and form protective space against pathogenic viruses, bacteria and other predators. This chitin is an example of unique biomaterial as source of substances with antibiotic properties. Traditionally, the attention of researchers was exclusively drawn to lipophilic bromotyrosines, the extraction methods of which were based on the use of organic solvents only. Alternatively, we have used in this work a biomimetic water-based approach, because in natural conditions, sponges actively extrude bromotyrosines that are miscible with the watery environment. This allowed us to isolate 3,5-dibromoquinolacetic acid from an aqueous extract of the dried demosponge Aplysina aerophoba and compare its antimicrobial activity with the same compound obtained by the chemical synthesis. Both synthetic and natural compounds have shown antimicrobial properties against clinical strains of Staphylococcus aureus, Enterococcus faecalis and Propionibacterium acnes.

Supplementary information: The online version contains supplementary material available at 10.1007/s00339-020-04167-0.

Keywords: Antibacterial; Biomimetics; Bromotyrosines; Chitin; Secondary metabolites; Spherulocytes; Sponges.

Fig. 1

Light microscopy image (a) of the bromotyrosine-producing reddish-coloured spherulocytes localized within chitinous skeletal fibres of Ianthella flabelliformis verongiid demosponge. They can degenerate and apparently release bromotyrosines-rich contents into the intercellular matrix and further into surrounding seawater. These cells remain to be well visible also using scanning electron microscopy (b)

Fig. 2

Chemical structures of compounds 1–3

Scheme 1

Synthesis of 3,5-dibromoquinolacetic acid (2). Reagents and conditions: a Br₂, AcOH, rt, 72 h; b HNO₃, AcOH, 10 °C, 15 h

Fig. 3

Growth inhibition by samples represented in Table 1 against S. aureus (a–c); P. acnes (d) and K. pneumoniae (e) (scale bar 1 cm)