Magnesium Oxide Nanoparticles Curb Staphylococcus aureus Biofilms from Diabetic Foot Ulcers

Magnesium oxide nanoparticles reduced biofilm formation by clinical Staphylococcus aureus isolates recovered from diabetic foot ulcers and significantly suppressed two key biofilm-associated genes, according to a laboratory study published in BMC Microbiology. The work, led by researchers including Mohammad Javad Roustaye Gourabi and Ali Hashemi, offers preliminary evidence that magnesium oxide nanoparticles (MgO-NPs) could serve as an adjunctive strategy against biofilm-associated infections, which tolerate conventional antibiotics and complicate the management of diabetic foot wounds.

The study evaluated six clinical S. aureus isolates from diabetic foot ulcers together with the reference strain S. aureus ATCC 25923. The nanoparticles were synthesized using a hydrothermal sol-gel method and characterized through a battery of analytical techniques, including X-ray diffraction, UV-Vis spectroscopy, transmission electron microscopy, field-emission scanning electron microscopy, energy-dispersive X-ray analysis, BET surface area measurement, and dynamic light scattering. This characterization confirmed the physical properties of the particles before biological testing began.

Antibacterial activity was measured by determining minimum inhibitory concentrations, which ranged from 512 to 1024 micrograms per milliliter across the isolates. The corresponding strain-specific sub-MIC concentrations, meaning levels below those needed to stop visible growth, ranged from 256 to 512 micrograms per milliliter. Testing bacteria at sub-MIC levels allowed the researchers to ask whether the nanoparticles directly interfere with biofilm formation rather than simply killing or slowing the growth of the bacteria.

Biofilm inhibition was assessed with the microtiter plate crystal violet assay, a standard method that stains the biomass attached to plastic surfaces. Exposure to the strain-specific sub-MIC concentrations of MgO-NPs reduced biofilm biomass by an average of approximately 54 percent across the six clinical isolates. The authors caution, however, that the crystal violet assay cannot completely distinguish a direct antibiofilm effect from reductions that arise simply because bacterial growth is slowed, an important limitation when interpreting the biomass results.

Polymerase chain reaction screening showed that all isolates carried icaA, icaC, and icaD, while icaB was present in 83.3 percent of the strains. Quantitative real-time PCR then measured how expression of icaA and icaD changed after exposure to the strain-specific sub-MIC nanoparticle concentrations, revealing significant downregulation of both genes in all tested strains.

The magnitude of the gene suppression depended on the concentration used. Among strain-gene observations exposed to 256 micrograms per milliliter, mean expression reductions were 40.6 percent, while observations exposed to 512 micrograms per milliliter showed mean reductions of 59.5 percent. Because these concentrations represented 0.5 times the MIC of different strains, the authors note that the two exposure levels were not directly comparable doses within any single isolate, a nuance that matters for interpreting the dose-response pattern.

Safety toward human cells was examined with an MTT assay using L929 fibroblast cells, a common in vitro cytocompatibility screen. Cell viability remained above 90 percent at nanoparticle concentrations up to 512 micrograms per milliliter, the highest level tested, suggesting acceptable cytocompatibility under the specific conditions of the experiment.

The authors frame their conclusions carefully. They describe the findings as preliminary evidence supporting the potential of MgO-NPs as an adjunctive approach for managing biofilm-associated S. aureus infections in diabetic foot ulcers, while explicitly listing the study’s constraints: the small number of clinical isolates, limited experimental controls, and the interpretive limits of the crystal violet assay. They emphasize that larger studies incorporating appropriate controls, comprehensive mechanistic analyses, and in vivo models are required to validate the results and clarify the underlying mechanisms.

For now, the study adds to a growing body of research on nanoparticle approaches to biofilm-related infections in diabetic foot ulcers, a field in which related reviews and systematic analyses continue to appear. The concrete takeaways from this work are specific and measured: MgO-NPs at 512 to 1024 micrograms per milliliter inhibited bacterial growth, sub-MIC exposures cut biofilm biomass by roughly half on average, icaA and icaD expression fell significantly in every strain tested, and fibroblast viability stayed above 90 percent up to 512 micrograms per milliliter. Whether these laboratory effects translate into clinical benefit for patients with infected diabetic foot ulcers remains an open question that only larger, controlled, and ultimately in vivo and clinical studies can answer.

Subject of Research: Laboratory evaluation of magnesium oxide nanoparticles against biofilm formation and biofilm gene expression in Staphylococcus aureus isolates from diabetic foot ulcers.

Article Title: Antibiofilm activity and downregulation of icaA and icaD expression by magnesium oxide nanoparticles in clinical Staphylococcus aureus isolates from diabetic foot ulcers

Article References: Roustaye Gourabi, M. J., Hashemi, A., Goudarzi, M., Yasbolaghi Sharahi, J., Fayyazi, A., Shivaee, A., & Hajikhani, B. (2026). Antibiofilm activity and downregulation of icaA and icaD expression by magnesium oxide nanoparticles in clinical Staphylococcus aureus isolates from diabetic foot ulcers. BMC Microbiology. https://doi.org/10.1186/s12866-026-05750-w

Image Credits: AI Generated

DOI: 10.1186/s12866-026-05750-w

Keywords: magnesium oxide nanoparticles, Staphylococcus aureus, diabetic foot ulcers, biofilm, icaA, icaD, antibacterial activity, minimum inhibitory concentration, quantitative real-time PCR, cytocompatibility, nanoparticle synthesis, sub-MIC exposure