A novel cyclic peptide CAP-18 and its enantiomer cyclic D-CAP-18 as potential agents against multidrug-resistant bacteria

Background
Antimicrobial peptides (AMPs) represent promising candidates in the search for new antimicrobial agents. The increasing incidence of infections caused by multidrug-resistant (MDR) bacteria, together with the declining efficacy of existing antibiotics, highlights the urgent global need for novel therapeutics. CAP-18 is an α-helical peptide belonging to the cathelicidin family. Its enantiomer, D-CAP-18, also shows potential for drug development and optimization. Because linear peptides are often unstable in vivo, cyclization of both peptides was undertaken to improve stability. This study aimed to evaluate the antimicrobial activity of cyclic CAP-18 and cyclic D-CAP-18 against MDR bacteria.

Methods
Antimicrobial activity was assessed using broth microdilution assays to determine minimum inhibitory concentrations (MICs) of the cyclic peptides against American Type Culture Collection (ATCC) reference strains and a panel of well-characterized clinical MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing strains. Four MDR E. coli and five MDR K. pneumoniae clinical isolates were tested.

Results
Both cyclic CAP-18 and cyclic D-CAP-18 exhibited greater activity against Gram-negative than Gram-positive bacteria. MIC values for cyclic CAP-18 against E. coli ranged from 2 to 8 mg/L, while cyclic D-CAP-18 showed MICs of 2 to 4 mg/L. Against K. pneumoniae, cyclic CAP-18 demonstrated MICs of 4 to 32 mg/L, and cyclic D-CAP-18 showed MICs of 4 to 16 mg/L.

Conclusion
Cyclic CAP-18 and cyclic D-CAP-18 display promising antimicrobial activity against MDR Gram-negative bacteria, including both ATCC reference strains and clinical isolates. These preliminary findings support their potential as candidates for further antimicrobial drug development.