Balsacone C, a New Antibiotic Targeting Bacterial Cell Membranes, Inhibits Clinical Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA) Without Inducing Resistance

Abstract

New options are urgently needed for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Balsacone C is a new dihydrochalcone extracted from Populus balsamifera that has been reported previously as being active against Staphylococcus aureus. Here, we evaluate the antibacterial activity of balsacone C against MRSA. Thirty-four (34) MRSA isolates were obtained from hospitalized patients; these isolates were then characterized for their resistance. Most of these MRSA (>85%) were resistant to penicillin, amoxicillin/clavulanic acid, ciprofloxacin, moxifloxacin, levofloxacin, clindamycin, erythromycin, and cefoxitin as well as being sensitive to linezolid, trimethoprim/sulfamethoxazole, rifampicin, and gentamicin. When tested against all MRSA isolates and various gram-positive bacteria, the antibacterial activity of balsacone C produced a MIC of 3–11.6 mg/mL. We observed no resistant isolates of MRSA (against balsacone C) even after 30 passages. Microscopy fluorescence showed that bacteria cell membrane integrity was compromised by low concentrations of balsacone C. Scanning electron microscope (SEM) confirmed balsacone C–provoked changes in the bacterial cell membrane and we find a dose-dependent release of DNA and proteins. This loss of cellular integrity leads to cell death and suggests a low potential for the development of spontaneous resistance.

A traditional Ugandan Ficus natalensis bark cloth exhibits antimicrobial activity against methicillin-resistant Staphylococcus aureus

“…The time‐kill kinetics assay demonstrated that the active antimicrobial compound(s) might have diffused from the bark cloth, but visualization of the fabric using SEM showed biofilms of cells with significant morphological changes in cellular ultrastructure. Bacterial cells became irregular in shape, with invaginations, holes and perforations, which is consistent with bacterial cytoplasmic membrane damage (Côté et al 2019…”

Superoxide Radical-Mediated Self-Synthesized Au/MoO3–x Hybrids with Enhanced Peroxidase-like Activity and Photothermal Effect for Anti-MRSA Therapy

“…2 In addition, some effective antibiotics (clindamycin and vancomycin) can trigger aberrant immunological reaction and other side effects. 3,4 As a consequence, the development of safe, high-efficiency and nonantibiotic antimicrobials against MRSA stains is urgently demanded. As of now, several new therapeutic strategies have proposed, such as photothermal antibacterial (PTA), 5,6 photodynamic antibacterial (PDA) 7,8 or chemodynamic antibacterial (CDA).…”

Synthesis of Asebogenin and Balsacone A Precursor by a Novel Synthetic Strategy: Recent Opportunities for and Challenges of Total Synthesis of Balsacone A

“…Researchers, therefore, examined the extracts obtained from the buds of Populus species for their antimicrobial activity and they isolated from the buds of P. balsamifera the new dihydrochalcone derivatives, known as balsacones [ 16 , 17 ]. The analysis, synthesis, and pharmacological properties of balsacones have been thoroughly studied [ 18 , 19 , 20 ]. In a recent study investigating the biological role of balsacones in treating psoriasis, promising anti-inflammatory and antioxidant effects that may promote clinical recovery in patients with psoriasis were reported.…”