# Spirulina platensis as a novel natural antimicrobial against macrolide-resistant Mycoplasma gallisepticum in poultry

**Authors:** Sabrina Zidi, Nadine Khadraoui, Rym Essid, Imen Chniba, Sarra Abassi, Salim Chibani, Maher Gazbar, Behija Mlik, Hédi Gazbar, Wassim Y. Almawi, Boutheina Ben Abdelmoumen Mardassi

PMC · DOI: 10.3389/fmicb.2026.1769010 · Frontiers in Microbiology · 2026-02-18

## TL;DR

Spirulina platensis shows promise as a natural antimicrobial against drug-resistant Mycoplasma gallisepticum in poultry.

## Contribution

Spirulina platensis is proposed as a novel, non-toxic antimicrobial with a unique mechanism against macrolide-resistant Mycoplasma gallisepticum.

## Key findings

- Spirulina platensis inhibited 65% of isolates at 250 μg/mL or lower.
- Spirulina showed no cytotoxicity up to 4,000 μg/mL with a high selectivity index.
- It exhibited weak correlations with conventional antibiotics, indicating a distinct activity profile.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Chemicals:** doxycycline (PubChem CID 54671203), oxytetracycline (PubChem CID 54675779), tylosin (PubChem CID 5280440), tilmicosin (PubChem CID 5282521), Aivlosin (PubChem CID 56840638)

## Full-text entities

- **Diseases:** Cytotoxicity (MESH:D064420), air sacculitis (MESH:D004618), infections (MESH:D007239), conjunctivitis (MESH:D003231), viral infections (MESH:D014777), MG (MESH:D009175), infectious diseases (MESH:D003141), nasal discharge (MESH:D019522), Bacterial (MESH:D001424), facial swelling (MESH:D004487), AMR (MESH:D060467), sinusitis (MESH:D012852), stunted growth (MESH:D006130), respiratory disease (MESH:D012140), coccidiosis (MESH:D003048), Newcastle disease (MESH:D009521)
- **Chemicals:** L-arginine (MESH:D001120), quinolone (MESH:D015363), macrolide (MESH:D018942), MTT (MESH:C070243), TIL (MESH:C052319), CMIc (MESH:C066546), penicillin (MESH:D010406), tetracycline (MESH:D013752), phenol red (MESH:D010637), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), Frey's broth (-), DMSO (MESH:D004121), flavonoids (MESH:D005419), glucose (MESH:D005947), PBS (MESH:D007854), beta-lactams (MESH:D047090), lipid (MESH:D008055), glycopeptides (MESH:D006020), CO2 (MESH:D002245), essential fatty acids (MESH:D005228), polysaccharides (MESH:D011134), formazan (MESH:D005562), methanol (MESH:D000432), DOX (MESH:D004318), enrofloxacin (MESH:D000077422), OXY (MESH:D010118), cholesterol (MESH:D002784), nitric oxide (MESH:D009569), spiramycin (MESH:D015572), alkaloids (MESH:D000470), essential amino acids (MESH:D000601), Tetracyclines (MESH:D013754), terpenoids (MESH:D013729), essential oils (MESH:D009822), AIV (MESH:C509469), TYL (MESH:D015645), carotenoids (MESH:D002338), tetrazolium (MESH:D013778)
- **Species:** Homo sapiens (human, species) [taxon 9606], Staphylococcus aureus (species) [taxon 1280], Punica granatum (granado, species) [taxon 22663], Gallus gallus (bantam, species) [taxon 9031], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Pseudomonas aeruginosa (species) [taxon 287], Mus musculus (house mouse, species) [taxon 10090], Bacillus subtilis (species) [taxon 1423], Limnospira platensis (species) [taxon 118562], Kangiella shandongensis (species) [taxon 2763258], Meleagris gallopavo (common turkey, species) [taxon 9103], Campylobacter jejuni (species) [taxon 197], Mycoplasmoides gallisepticum (species) [taxon 2096]
- **Mutations:** Arg177Lys, A2058G
- **Cell lines:** ATCC15302 — Homo sapiens (Human), Hybrid cell line (CVCL_1S96), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493)

## Full text

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## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12959242/full.md

## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC12959242/full.md

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Source: https://tomesphere.com/paper/PMC12959242