The Antibacterial Synthetic Flavonoid BrCl-Flav Exhibits Important Anti-Candida Activity by Damaging Cell Membrane Integrity

Abstract

Infections caused by Candida are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with Candida infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. The aim of this study was to explore the antifungal potential of BrCl-flav-a representative of a new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against four Candida clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration along with the time kill assay indicated a strong antifungal effect of BrCl-flav against C. albicans, C. parapsilosis, C. krusei and C. glabrata. The investigation of anti-Candida mechanism of action using fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages leading to cell lysis. BrCl-flav also showed important anti-virulence properties against Candida spp., inhibiting biofilm formation and yeast to hyphal transition. A strong synergistic antifungal effect against C. albicans strain was observed when BrCl-flav was used in combination with fluconazole. BrCl-flav has a good potential to develop new effective antifungal agents in the context of Candida spp. multidrug resistance phenomenon.

Plant Natural Products as Antimicrobials for Control of Streptomyces scabies: A Causative Agent of the Common Scab Disease

“…The SEM and TEM images of S. scabies-treated cells showed that the four flavonoids under investigation caused significant damage to cell membranes. This was not surprising given the previous reports in the literature (Zhang L. L. et al, 2020;Zhang S. et al, 2020;Babii et al, 2021;Yuan et al, 2021). The current theory for flavonoid-membrane interactions postulates that flavonoids intercalate into membrane bilayers and shift the gel-to-liquid crystal transition temperature of the phospholipids to a more rigid, gel-like state.…”

Synthetic Flavonoid BrCl-Flav—An Alternative Solution to Combat ESKAPE Pathogens

“…In this context, we hypothesize that BrCl-flav—a representative of a new class of synthetic sulfur containing tricyclic flavonoids with different halogen substituent at the benzopyran core—could be a reliable candidate for the formulation of new effective antimicrobials. We previously reported the important bactericidal and fungicidal effects of BrCl-flav [ 23 , 24 , 27 ]. However, no investigations were carried out on clinical bacterial isolates with different antibiotic resistance profiles.…”

“…DMSO served as a control. Samples (untreated and treated bacterial cells) were prepared for SEM analysis following the protocol previously described [ 23 ] and examined with a Tescan Vega II SBH microscope using the secondary electron detector at an acceleration voltage of 30 kV.…”

“…Although we previously showed that BrCl-flav is an effective antimicrobial compound with strong bactericidal and fungicidal effects against S. aureus , E. coli and Candida spp. [ 23 , 24 ], no investigations were carried out against pathogenic bacterial strains. Therefore, in the present study we focus not only on the antibacterial activity of BrCl-flav against antibiotic-resistant clinical isolates including ESKAPE pathogens, but also on biofilm formation and the effects of combinations with traditional antibiotics, as well as the cytotoxicity and effects on inflammation that were never addressed before.…”

New Insights into the Antimicrobial Potential of Polyalthia longifolia—Antibiofilm Activity and Synergistic Effect in Combination with Penicillin against Staphylococcus aureus

“…The MIC was determined by the broth microdilution method, as previously described [ 16 , 17 ]. A concentration range of P. longifolia extracts between 0.0097 and 20 mg/mL was tested, with dimethyl sulfoxide (DMSO, Merck, Darmstadt, Germany) as solvent.…”