Anti-adhesive activity of LyeTx I mnΔK, a short peptide derived from the Brazilian spider Lycosa erythrognatha venom, against quinolone-resistant uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPECs) is becoming an increasing widespread pathogen, particularly due to the emergence of quinolone resistance. In this context, antimicrobial peptides (AMPs) are goods prototype against drug resistant UPECs. Here, we evaluated LyeTx I mnΔK, a short, modified peptide derived from the Brazilian spider Lycosa erythrognatha venom, against quinolone-resistant UPECs. The peptide was characterized for its antibacterial activity through of minimum inhibitory concentration (MIC), minimum bactericidal concentrations (MBC), anti-adhesive action and anti-biofilm effect. In silico analysis was performed to study the interaction of peptide with E. coli FimH adhesin and safety was evaluated in vitro and in vivo studies. LyeTx I mnΔK showed MIC50 and MBC50 of 2 μM and 8 μM, respectively. The peptide displayed anti-adhesive action in sub-inhibitory concentrations and inhibited the adhesion of quinolone-resistant UPECs cells on the surface of urinary catheter. In silico studies suggested that LyeTx I mnΔK was able to bind to hydrophobic hole of mannose-binding pocket of FimH, a membrane protein helping in UPECs adhesion and biofilm formation. The compound exhibits low toxicity in vitro and in vivo, despite increasing creatinine levels and altering renal histology at the highest dose tested in mice (10 mg/kg). Moreover, the antimicrobial potential of LyeTx I mnΔK was reduced after incubation with urine. Overall, our findings suggest that LyeTx I mnΔK is an effective prototype for the development of novel anti-adhesive molecules against UPEC, particularly after chemical modifications aimed reducing its toxicity and increasing its stability.