Bioactive molecules analogous to Stigmurina with antimicrobial, antibiofilm, and healing Properties.
Antimicrobial peptide; Biofilm; Cytotoxicity; Antifungal activity; Wound healing.
Antimicrobial resistance has become increasingly alarming given the risks it poses
to the global economy and public health. The irrational use of antimicrobials has
contributed greatly to this microbial resistance to conventional drugs. Given this problem
and the chronic nature of infections with and by biofilm formation in skin wounds,
antimicrobial peptides (AMPs) emerge as promising alternatives for the development of
new drugs. StigA15 and StigA28 are peptides analogous to Stigmurin, found in the venom
of the scorpion Tityus stigmurus, and correspond to promising AMPs obtained through
rational molecule design. In this study, pharmacokinetic activity and molecular dynamics
simulation (in silico) were evaluated, in addition to cytotoxicity, minimum inhibitory
concentration, minimum bactericidal concentration, biofilm - for bacteria and fungi (in
vitro) - and healing activity in uninfected wounds (in vivo). In this context, the objective
of the study was to obtain data on the applicability and safety of biomolecules in
biological, antimicrobial, and healing activity. It was through changes in the amino acid
chain of stigmurin, designed by our research group using bioinformatics
(FFSLIPSLVGGLISAFK-NH₂), that the analog peptides StigA15
(FFSLIPKLVGGLIKAFK-NH₂)
and StigA28 (FFKLIPKLVGKLIKAFK-NH₂)
emerged. The substitutions of glycine for lysine increased the net charge of the analogues,
reduced cytotoxicity, intensified the peptide-microorganism interaction, and conferred
promising antimicrobial activity to both peptides, tested against different Gram-positive,
Gram-negative bacteria, and yeasts (patent granted by the INPI, No. BR 102015029044-
6). As a result, a favorable spectrum of action of PAMs was observed both in the
minimum inhibitory concentration (MIC) and in antibiofilm activity, especially in the late
phase, in addition to a positive healing effect on uninfected wounds. The peptides StigA15
and StigA28 demonstrated potent antimicrobial activity against Gram-positive, Gram
negative bacteria, and yeasts of the genus Candida spp. at non-cytotoxic concentrations.
In addition, they exhibited bactericidal and fungicidal effects, indicating a broad spectrum
of action. In murine models, they also promoted the healing of skin wounds, suggesting
their potential as bioactive agents with a dual function: antimicrobial and healing.