**6. Mechanisms of actions with antibiotic**

EOs' mechanism of action is poorly understood, but in general it depends on their chemical composition [8, 66, 84]. As antimicrobial resistance to antibiotics is increasing, scientists are currently exploring the ability of the plant extract to modify bacterial resistance against drugs [39]. The three main types of interactions that occur between the combination of antibiotic and EO are synergism, additivity, and antagonism [85]. Synergistic interaction is when the effect of the combined chemicals is greater than the effect of a chemical alone; additive interaction is when the sum of two chemicals is equal to the sum of chemical effect alone, while antagonism is when the whole effect of the two chemicals is less than the sum of effect of a single chemical alone [86]. In a study performed using the tea tree EO against the MDR bacteria, when a combination of tea tree EO with antibiotic (e.g., oxacillin) was tested on the bacteria, in particular the MRSA, a high synergistic index in the sub-inhibitory concentration was recorded [75]. This indicates that the EO can be used to overcome bacterial resistance to antibiotic. The synergism level increases when the combined effect is higher than the individual effect in the combination therapy [39].

Combination therapy is a new method that combines antibiotics and EO to kill resistant bacteria, via enhancement of the antimicrobial activity [39, 87]. Moreover, EOs have more components possessing different mechanisms of actions for many targets than antibiotics that have only one target. Combination therapy would be useful and able to provide a new treatment option for resistance bacteria [39].
