Antibacterial, Antibiofilm, and Antiviral Farnesol-Containing Nanoparticles Prevent Staphylococcus aureus from Drug Resistance Development

Abstract

Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development.

The effect and mechanism of iodophors on the adhesion and virulence of Staphylococcus aureus biofilms attached to artificial joint materials

“…In vitro, the scavenging effect of some disinfectants on biofilms has been studied. A high concentration of farnesol (30 mM) shows antimicrobial properties against bacterial biofilms [ 36 , 37 ]. Hypochlorous acid, a powerful disinfectant, can break bacterial biofilms and may be useful in the treatment of orthopaedic fixative infections [ 38 ].…”

The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage

“…As mentioned above, the polyprenol salvage pathway was first observed more than 25 years ago, but the enzymes responsible in animals or any pathogen are still unident ified [72,80]. Despite this, the interest in this pathway for the treatment of several human pathologies, ranging from osteonecrosis to infectious diseases, is increasing [92,93]. As a consequence, it is impractical to mention here everything published in this field, and we needed to make a selection of those reports that best illustrated the topics discussed, with a focus on biomedical problems.…”

Farnesol and Selected Nanoparticles (Silver, Gold, Copper, and Zinc Oxide) as Effective Agents Against Biofilms Formed by Pathogenic Microorganisms

“…Farnesol can also interfere with the rate of glycan synthesis in the biofilm matrix, impairing biofilm establishment. 20,21 For example, in Streptococcus mutans, momentary exposure to farnesol influenced the growth and metabolism of bacteria by disturbing the bacterial membrane and elevating the polysaccharide content within streptococcal biofilms. 20 Studies focused on the mode of action of terpenic alcohols (including farnesol) on Staphylococcus aureus suggested that cell membrane damage may be one of the main antibacterial mechanisms.…”