Essential Oils: A Natural Weapon against Antibiotic-Resistant Bacteria Responsible for Nosocomial Infections

Abstract

The emergence of antibiotic-resistant bacteria has become a major concern worldwide. This trend indicates the need for alternative agents to antibiotics, such as natural compounds of plant origin. Using agar disc diffusion and minimum inhibitory concentration (MIC) assays, we investigated the antimicrobial activity of Citrus aurantium (AEO), Citrus x limon (LEO), Eucalyptus globulus (EEO), Melaleuca alternifolia (TTO), and Cupressus sempervirens (CEO) essential oils (EOs) against three representatives of antibiotic-resistant pathogens and respective biofilms: vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Using the checkerboard method, the efficacy of the EOs alone, in an association with each other, or in combination with the reference antibiotics was quantified by calculating fractional inhibitory concentrations (FICs). All the EOs displayed antibacterial activity against all strains to different extents, and TTO was the most effective. The results of the EO–EO associations and EO–antibiotic combinations clearly showed a synergistic outcome in most tests. Lastly, the effectiveness of EOs both alone and in association or combination against biofilm formed by the antibiotic-resistant strains was comparable to, and sometimes better than, that of the reference antibiotics. In conclusion, the combination of EOs and antibiotics represents a promising therapeutic strategy against antibiotic-resistant bacteria, even protected inside biofilms, which can allow decreasing the concentrations of antibiotics used.

Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

“…The term ‘essential oil’ was first used by Paracelsus von Hohenheim, a medieval Swiss physician [ 102 ]. EOs include terpenes, aldehydes, phenolic, terpenoids, and other aromatic constituents that have demonstrated antimicrobial activities [ 99 , 100 , 101 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. EOs mainly contribute to the disruption of the bacterial cell membrane and inhibition of the efflux pump responsible for certain AMR in Gram-negative bacteria [ 100 , 105 , 114 , 115 , 116 , 117 ].…”

“…EOs include terpenes, aldehydes, phenolic, terpenoids, and other aromatic constituents that have demonstrated antimicrobial activities [ 99 , 100 , 101 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. EOs mainly contribute to the disruption of the bacterial cell membrane and inhibition of the efflux pump responsible for certain AMR in Gram-negative bacteria [ 100 , 105 , 114 , 115 , 116 , 117 ]. Other documented modes of action include inhibition of the peptidoglycan layer synthesis of bacterial cell walls by binding to PBPs for Gram-positive bacteria [ 105 , 114 , 115 , 116 , 117 ].…”

“…EOs mainly contribute to the disruption of the bacterial cell membrane and inhibition of the efflux pump responsible for certain AMR in Gram-negative bacteria [ 100 , 105 , 114 , 115 , 116 , 117 ]. Other documented modes of action include inhibition of the peptidoglycan layer synthesis of bacterial cell walls by binding to PBPs for Gram-positive bacteria [ 105 , 114 , 115 , 116 , 117 ]. Recent advances in genomics and proteomics demonstrated the ability of EOs to inhibit biofilm formation and quorum sensing (QS) production and increase the expression of oxidative stress proteins [ 100 , 105 ].…”

“…Other documented modes of action include inhibition of the peptidoglycan layer synthesis of bacterial cell walls by binding to PBPs for Gram-positive bacteria [ 105 , 114 , 115 , 116 , 117 ]. Recent advances in genomics and proteomics demonstrated the ability of EOs to inhibit biofilm formation and quorum sensing (QS) production and increase the expression of oxidative stress proteins [ 100 , 105 ]. Eos, either alone, in combination, or associated with other antibiotics, demonstrated effective antibacterial activity against different pathogens, including MDR bacteria [ 100 , 105 , 118 ].…”

“…Recent advances in genomics and proteomics demonstrated the ability of EOs to inhibit biofilm formation and quorum sensing (QS) production and increase the expression of oxidative stress proteins [ 100 , 105 ]. Eos, either alone, in combination, or associated with other antibiotics, demonstrated effective antibacterial activity against different pathogens, including MDR bacteria [ 100 , 105 , 118 ]. More in-depth studies are necessary to discover and identify novel EO compounds that may one day be used in clinical practice [ 100 , 103 ].…”