Tetrabutylammonium isolated from Anthopleura cascaia sea anemone venom (São Sebastião, Brazil) and its effects against multiresistant Klebsiella pneumoniae

The increase in bacterial resistance has been frequently observed in clinics, making the search for new antimicrobial agents necessary. In this context, marine animals represent a rich source of bioactive molecules with potential antimicrobial effects. This study evaluated the antimicrobial properties of compounds extracted from sea anemone venoms against multidrug-resistant strains of bacteria Acinetobacter baumannii , Escherichia coli , and Klebsiella pneumoniae . Through an antibacterial activity-guided fractionation, an inhibition halo was observed in a disc-diffusion assay using Anthopleura cascaia venom against clinical isolate of K. pneumoniae . Subsequently, the venom was fractionated by HPLC, and the resulting fractions were subjected to a microdilution assay. One active fraction was identified by mass spectrometry as tetrabutylammonium (TBA). The compound was then synthetically obtained, and maintained the activity, confirming its identity. Synthetic TBA was tested against several resistant clinical isolates of K. pneumoniae , revealing different growth inhibition profiles among the strains. The most susceptible strains were further evaluated in a biocidal assay, which demonstrated a stronger effect against three clinical isolates, for which no therapeutic options remained available. Using in silico approaches, we observed a potential inhibition of efflux pump mechanisms, which will be further investigated. Finally, TBA showed low toxicity potential. Although TBA is a well-known compound, its antibacterial activity against clinical multidrug-resistant K. pneumoniae isolates is a novel finding, highlighting its potential as a new therapeutic option for combatting infections resistant to conventional antibiotics, particularly in cases with no remaining treatment alternatives.