Eucalyptus globulus residues inhibiting both MRSA and VRE in vitro and in vivo

Eucalyptus globulus fruit is an important source of eucalyptus essential oil, but its non-volatile components are discarded as by-products. To comprehensively use plant residues, their antibacterial components and mechanisms against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) were systematically investigated for the first time. As a result, the 60 % and 95 % ethanol extracts of E. globulus fruit inhibited MRSA and VRE with MICs = 8 μg/mL. Furthermore, they scavenged biofilms and altered bacterial surface morphology in vitro . Through UHPLC-Q-TOF-MS/MS, network pharmacology analysis, and experiments, phloroglucinols may generate antibacterial bioactivity by acting on the bacterial cell membrane structure, affecting the adhesion between bacteria and host cells. Therefore, the bioactive components of E. globulus fruits are not susceptible to developing resistance, owing to their multi-targeted action against bacteria. In addition, the bioactive components of E. globulus fruits promote the recovery of mouse wounds after methicillin-resistant Staphylococcus aureus (MRSA) infection. • Eucalyptus globulus residues inhibit MRSA and VRE. • The first in vitro and in vivo antibacterial evaluation of non-volatile fractions. • The non-volatile fractions altered bacterial biofilm and surface. • Phloroglucinols target bacterial cell membranes. • The non-volatile fraction enhanced wound recovery in MRSA-infected mice.