Platanosides, a Promising Class of Plant-Derived Antibiotics, Are Effective against a Suite of Clinically Derived MDR and Drug-Sensitive <i>Staph</i> and <i>Strep</i> spp.

Systemic multidrug-resistant bacterial infections have become a global public health priority due to the diminished efficacy of standard antibiotic regimens and can lead to sepsis, which is among the leading causes of death (11 million/year) and years of lost life worldwide. We report an effective and well-defined antibiotic equimolar mixture of the platanosides 1–4 that is as effective as its constituent parts and is active against multidrug-resistant Staphylococcus and Streptococcus spp. The platanosides can be easily and inexpensively manufactured in good purity from sycamore tree ( Platanus spp.) leaves, making them a viable option as a drug to control multidrug-resistant infections in low- and middle-income countries. The platanosides 1–4 exhibited activity against clinically derived Staphylococcus aureus (methicillin-resistant, vancomycin-resistant, and vancomycin-intermediate) with minimal inhibitory concentration values of 0.5–16 μg/mL. The minimal inhibitory concentration values against clinically derived Streptococcus spp. were 2, 1, 0.06, and 1 μg/mL against Streptococcus mitis, Streptococcus paramsanginis, Streptococcus gordonii, and Streptococcus pneumoniae, respectively. Time-kill studies of the platanosides are reported. The proposed molecular targets and unique polypharmacology of the platanosides 1–4 are also discussed.