Significance and Impact of the Study: Plant-derived antimicrobial natural compounds (PNACs) have been considered as alternatives to antibiotics in fighting pathogenic bacteria. However, evidence on the low resistance tendency of PNACs is very limited, and the synergistic antimicrobial activity of PNACs and antibiotics has been demonstrated in co-treatment only. It is the first time that the collateral relationship between bacterial adaptation and resistance to PNACs and antibiotics has been reported.