Synergistic Antibacterial Interaction of Geraniol and Biogenic Silver Nanoparticles on Methicillin-Resistant <i>Staphylococcus aureus</i>

Since ancient times, plants have been used in folk medicine to treat different diseases. Plants offer exceptional chemical diversity with a wide range of biological activities, and have therefore been the most promising sources for the discovery and development of drugs, including antimicrobial agents. This study reports the antibacterial effect of geraniol (GER), alone and in combination with biogenic silver nanoparticles (bioAgNPs), produced using the aqueous extract of <i>Trichilia catigua</i> bark, against planktonic and sessile cells of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), one of the main opportunistic and potentially fatal human pathogens. GER had a time-dependent bactericidal effect on planktonic cells, impairing the cell membrane integrity. In addition, GER inhibited the staphyloxanthin production, and molecular docking analyses supported the in silico affinity of GER to dehydrosqualene synthase (CrtM) and 4,4′-diaponeurosporen-aldehyde dehydrogenase (AldH), which are key enzymes within the pigment biosynthesis pathway in <i>S. aureus</i>. GER treatment increased the sensitivity of MRSA to hydrogen peroxide killing. GER displayed synergism with bioAgNPs against planktonic and sessile cells, inhibiting bacterial adhesion and the viability of biofilms formed on abiotic surfaces. MRSA planktonic and sessile cells treated with GER or GER/bioAgNPs displayed severe morphological and ultrastructural alterations. Notably, neither GER nor its combination caused in vitro and in vivo toxicity in mammalian cells and <i>Galleria mellonella</i> larvae, respectively. These findings suggest that the combination of GER/bioAgNPs may be a promising strategy to control MRSA infections.