In an article entitled, ‘Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics’ published in September 9, 2013, issue of PNAS  (doi:10.1073/pnas.1310459110), the lead author Jessica D. Podol with four other associates from the Department of Chemistry and Biochemistry, University of Colorado, USA, have synthesized a compound that can boost the activity of methicillin against methicillin-resistant Staphylococcus aureus (MRSA). MRSA continues to pose a major public health threat, despite the use of antibiotic resistance-modifying agents, which can help restore antibiotic efficacy by inhibiting microbial enzymes that degrade antibiotics. Taking cues from a natural strategy for the synthesis of plant-derived resistance-modifying agents, the researchers developed a method to rapidly synthesize a library of 120 polycyclic indoline alkaloids with 26 distinct chemical backbones and diverse functional groups. The authors screened the library for compounds that boosted the activity of methicillin against a multi-drug-resistant MRSA strain and found that a tricyclic compound called Of1 effectively rendered the resistant bacterial strain sensitive to the antibiotic. Furthermore, the authors report that Of1 potentiated a range of β-lactam antibiotics against MRSA but showed no such supportive effect on β-lactams against a methicillin-sensitive S. aureus strain. The compound boosts the anti-MRSA efficacy of other antibiotics, such as tetracyclin, ciprofloxacin, and vancomycin. In addition, Of1 (minimally toxic to mammalian cells at clinically appropriate concentrations) did not directly stop the proliferation of methicillin-sensitive or -resistant S. aureus, suggesting an indirect mechanism of action. According to the authors, Of1 might represent a promising weapon in microbiologists’ arsenal against MRSA. [summarized by Samsad Razzaque, Research Associate at Plant Bioth lab., DU]