Banca de QUALIFICAÇÃO: DAVID HENRIQUE XAVIER BARBOSA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : DAVID HENRIQUE XAVIER BARBOSA
DATE: 13/03/2026
TIME: 14:00
LOCAL: VIDEOCONFERÊNCIA
TITLE:

Peptides derived from TsAP-2 exhibit potential antifungal activity against Candida species and promote wound healing both in vitro and in vivo

KEY WORDS:

Antimicrobial peptides; scorpion venom; Tityus stigmurus; Tityus serrulatus.

PAGES: 131
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Antimicrobial drug resistance has become increasingly common, mainly due to resistance mechanisms and the irrational use of these medications. This scenario challenges science to develop new antimicrobial agents. In this context, Antimicrobial Peptides (AMPs) emerge as a promising alternative. From modifications in the primary sequence of TsAP-2, an AMP identified in the venom glands of the scorpions Tityus stigmurus and Tityus serrulatus, with antimicrobial and wound-healing activity, the analog peptides TsAP-2 A33, TsAP-2 A34, and TsAP-2 A35 were generated by substituting specific amino acids with lysine and/or arginine, aiming to increase cationicity, alpha-helical conformation, and potentiation of antimicrobial activity. These peptides showed low hemolytic activity at concentrations below 9.375 µM and a safety profile in L-929 cells up to 8 µM, as well as good tolerability in the prediction of pharmacokinetic and toxicological characteristics. They also demonstrated the ability to reduce the scratch area by approximately 80% in an in vitro cell migration assay and to promote in vivo wound healing with up to 84% wound reduction. These peptides exhibited relevant antibacterial activity against different Gram-positive strains and an expanded spectrum of action against Gram-negative bacteria compared to the native peptide, with MIC values ranging from 2.34 to 9.37 µM. In a pre-formed Staphylococcus aureus biofilm disruption assay, the analogs promoted significant biofilm disorganization of up to 81.05% at a concentration of MIC × 8 (37.5 µM). When associated with the antimicrobial ceftazidime, these peptides showed a synergistic effect against P. aeruginosa strains. In addition, the analog peptides demonstrated strong antifungal activity, with MIC values ranging from 2.5 to 5 µM for Candida strains. In a growth kinetics assay, the peptides at concentrations equivalent to the MIC and above the MIC caused sustained reduction of fungal growth over 24 hours of incubation, with statistically significant differences observed from 12 h onward, confirming their fungicidal action. Additionally, it was observed that these peptides may act at the level of the fungal cell membrane, since affinity for exogenous ergosterol was detected in an in vitro assay and also inferred through affinity for fungal cell membrane targets in in silico molecular docking analyses. In summary, TsAP-2 analog peptides demonstrated acceptable biocompatibility at therapeutic concentrations, in addition to remarkable antimicrobial and wound-healing activity. Further studies are expected to continue from a translational perspective in order to consolidate these analog peptides as a promising alternative in the rational search for new antimicrobial drugs or adjuvants in therapy.

COMMITTEE MEMBERS:
Presidente - 3652554 - FRANCISCO CANINDE DE SOUSA JUNIOR
Externo à Instituição - HILZETH DE LUNA FREIRE PESSÔA - UFPB
Externa à Instituição - MANOELA TORRES DO RÊGO - UFRN