Abd El Ghany, Shimaa Salah HassanIbrahem, Reham AEL‑Gendy, Ahmed OsamaAbd El‑Baky, Rehab MahmoudMustafa, AhmadAzmy, Ahmed Farag2024-04-132024-04-132024-12https://doi.org/10.1186/s12879-024-09261-9http://repository.msa.edu.eg/xmlui/handle/123456789/5931Background A major worldwide health issue is the rising frequency of resistance of bacteria.Drug combinations are a winning strategy in fghting resistant bacteria and might help in protecting the existing drugs.Monolaurin is natural compound extracted from coconut oil and has a promising antimicrobial activity against Staphylococcus.aureus. This study aims to examine the efcacy of monolaurin both individually and in combination with β-lactam antibiotics against Staphylococcus aureus isolates. Methods Agar dilution method was used for determination of minimum inhibitory concentration (MIC) of monolau‑ rin against S.aureus isolates. Scanning electron microscope (SEM) was used to detect morphological changes in S. aureus after treatment with monolaurin. Conventional and Real-time Polymerase chain reaction (RT-PCR) were per‑ formed to detect of beta-lactamase (blaZ) gene and its expressional levels after monolaurin treatment. Combination therapy of monolaurin and antibiotics was assessed through fractional inhibitory concentration and time-kill method. Results The antibacterial activity of monolaurin was assessed on 115 S.aureus isolates, the MIC of monolaurin were 250 to 2000 µg/ml. SEM showed cell elongation and swelling in the outer membrane of S.aureus in the prescence of 1xMIC of monolaurin. blaZ gene was found in 73.9% of S.aureus isolates. RT-PCR shows a signifcant decrease in of blaZ gene expression at 250 and 500 µg/ml of monolaurin. Synergistic efects were detected through FIC method and time killing curve. Combination therapy established a signifcant reduction on the MIC value. The col‑ lective fndings from the antibiotic combinations with monolaurin indicated synergism rates ranging from 83.3% to 100%.In time-kill studies, combination of monolaurin and β-lactam antibiotics produced a synergistic efect. Conclusion This study showed that monolaurin may be a natural antibacterial agent against S. aureus, and may be an outstanding modulator of β-lactam drugs. The concurrent application of monolaurin and β-lactam antibiotics, exhibiting synergistic efects against S. aureus in vitro, holds promise as potential candidates for the development of combination therapies that target particularly, patients with bacterial infections that are nearly incurable.enS.aureus, Monolaurin, blaZ gene, Gene expression, SynergismArticlehttps://doi.org/10.1186/s12879-024-09261-9