Endophyte-produced antimicrobials: a review of potential lead compounds with a focus on quorum-sensing disruptors

Endophytes are defined as microorganisms which live in plant tissues without causing any apparent negative effects to the host plant. Endophytes have been considered rich sources for natural products since they produce an array of chemically diverse bioactive secondary metabolites. Consistent with the hypothesis that endophytes help the survival and growth of host plants by producing secondary metabolites, many compounds derived from endophytes exhibit potent antimicrobial activity. Interestingly, some endophytes have been reported to produce the same metabolites as the host plants, probably due to horizontal gene transfer. In this review, metabolites produced by endophytes as well as their host plants are briefly introduced, with the emphasis on their value as pharmaceutical lead compounds. We have defined lead compounds as secondary metabolites with antimicrobial activities with Minimal Inhibitory Concentration values less than 20 μM (5 μg/mL). The endophytic metabolites with antimicrobial activities are classified into two groups according to the mode of inhibition: (1) antibiotic metabolites that kill or inhibit growth of microorganisms (2) endophyte-derived compounds with inhibitory activity against quorum sensing. Disruption of quorum sensing, which is a microbial communication system, has recently emerged as a novel target for antibiotic development since it affords a new modality to reduce microbial infection. Although currently there are no commercially-available antibiotics derived from endophytes, it is expected that new antibiotics based on several modes of action will be developed and marketed due to increasing research emphasis in this field.