- Ashaimaa Y Moussa: Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, African Union Organization Street, Abbassia, Cairo, 11566, Egypt. ashaimaa_yehia@pharma.asu.edu.eg.
Multidrug microbial resistance is risking an annual loss of more than 10 million people' lives by 2050. Solutions include the rational use of antibiotics and the use of drugs that reduce resistance or completely obliterate them. Here endophytes come to play due to their high-yield production and inherent nature to produce antimicrobial molecules. Around 40%, 45% and 17% of antibacterial agents were obtained from fungi, actinomycetes, and bacteria, respectively, whose secondary metabolites revealed effectiveness against resistant microbes such as MRSA, MRSE, and Shigella flexneri. Endophyte's role was not confined to bactericidal effect but extended to other mechanisms against MDR microbes, among which was the adjuvant role or the "magic bullets". Scarce focus was given to antibiotic adjuvants, and many laboratories today just screen for the antimicrobial activity without considering combinations with traditional antibiotics, which means real loss of promising resistance combating molecules. While some examples of synthetic adjuvants were introduced in the last decade, the number is still far from covering the disused antibiotics and restoring them back to clinical use. The data compiled in this article demonstrated the significance of quorum sensing as a foreseen mechanism for adjuvants from endophytes secondary metabolites, which call for urgent in-depth studies of their molecular mechanisms. This review, comprehensively and for the first time, sheds light on the significance of endophytes secondary metabolites in solving AMR problem as AB adjuvants.