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

Héloïse Côté,Doria Grimard,François Simard,Mouadh Mihoub,Marie-Eve Ouellette,Lionel Ripoll,André Pichette,Jean Legault

doi:10.3389/fmicb.2019.02341

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.

Highlights

Infectious diseases are the second leading global cause of death in the world
An antibiogram of S. aureus and all isolates was performed with various classes of antibiotics – they include beta-lactam, fluoroquinolone, lincosamide, macrolide, cephalosporin, oxazolidone, sulfonamide, rifamycin, aminoglycoside and glycopeptide
The results indicated that S. aureus (ATCC 25923) was sensitive to all antibiotics tested except levofloxacin (Supplementary Tables S2, S3)

Summary

Introduction

Infectious diseases are the second leading global cause of death in the world. Across the globe, bacterial infections kill 700,000 people annually (World Health Organization [WHO], 2016), and by 2050, deaths attributable to antibiotic-resistant infections may even exceed cancerrelated deaths (Bagnoli et al, 2017). Novel Antibiotic Balsacone-C Inhibits MRSA remain a primary cause of infection-related mortality and represent a major global health care problem. This antibioticresistant bacteria was first identified within a health care setting around 1960, and it emerged in the community in the early 1990s (Vestergaard et al, 2019). Methicillin resistance in Staphylococcus aureus is due to the acquisition of the mobile genetic element SCCmec (mecA or mecC). This gene codes for a penicillin-binding protein (PBP) that makes the strain resistant to all beta-lactam antibiotics (Bagnoli et al, 2017). Novel antibiotics are required urgently to combat this lifethreatening pathogen (Laxminarayan et al, 2014; Assis et al, 2017; Subramani et al, 2017)

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Conclusion