Abstract
BACKGROUND: Antimicrobial resistance in Mycoplasma gallisepticum (MG) poses a significant threat to global poultry production, as traditional antibiotics, particularly macrolides, are becoming increasingly ineffective due to growing resistance. This study investigates Spirulina platensis as a natural antimicrobial candidate against macrolide-resistant MG strains. MATERIALS AND METHODS: We tested 64 field isolates, along with the reference strain ATCC 15302, using broth microdilution. Minimum inhibitory concentrations (MICs) were measured for conventional antibiotics (doxycycline, oxytetracycline, tylosin, tilmicosin, Aivlosin) and Spirulina extract. Principal Component Analysis and correlation matrices were employed to investigate therapeutic relationships, while cytotoxicity assays evaluated safety profiles. RESULTS: High resistance rates were observed for the macrolides tilmicosin (87.5%) and tylosin (68.75%). Spirulina platensis showed in vitro antimicrobial activity against the tested isolates, with MICs ranging from 3.9 to 1,000 μg/mL; 65% of isolates were inhibited at concentrations of 250 μg/mL or lower, indicating measurable activity and supporting further investigation as a natural antimicrobial compound. Correlation analyses indicated weak or negligible associations with conventional antibiotics (p < 2.2 × 10(-16)), reflecting a distinct activity profile. Additionally, Spirulina exhibited no cytotoxicity up to 4,000 μg/mL, with a selectivity index of 512.8, indicating a favorable in vitro safety profile. CONCLUSION: These findings suggest that Spirulina platensis acts as a uniquely mechanistic, non-toxic antimicrobial agent that can bypass existing resistance mechanisms. Further in vivo validation and mechanistic investigations are necessary to assess its potential as an alternative therapeutic option for poultry health management and combating antimicrobial resistance.