Peptaibol-Containing Extracts of Trichoderma atroviride and the Fight against Resistant Microorganisms and Cancer Cells

Fighting resistance to antibiotics and chemotherapeutics has brought bioactive peptides to the fore. Peptaibols are short α-aminoisobutyric acid-containing peptides produced by Trichoderma species. Here, we studied the production of peptaibols by Trichoderma atroviride O1 and evaluated their antibacterial and anticancer activity against drug-sensitive and multidrug-resistant bacterium and cancer cell lines. This was substantiated by an analysis of the activity of the peptaibol synthetase-encoding gene. Atroviridins, 20-residue peptaibols were detected using MALDI-TOF mass spectrometry. Gram-positive bacteria were susceptible to peptaibol-containing extracts of T. atroviride O1. A synergic effect of extract constituents was possible, and the biolo-gical activity of extracts was pronounced in/after the peak of peptaibol synthetase activity. The growth of methicillin-resistant Staphylococcus aureus was reduced to just under 10% compared to the control. The effect of peptaibol-containing extracts was strongly modulated by the lipoteichoic acid and only slightly by the horse blood serum present in the cultivation medium. Peptaibol-containing extracts affected the proliferation of human breast cancer and human ovarian cancer cell lines in a 2D model, including the multidrug-resistant sublines. The peptaibols influenced the size and compactness of the cell lines in a 3D model. Our findings indicate the molecular basis of peptaibol production in T. atroviride O1 and the potential of its peptaibol-containing extracts as antimicrobial/anticancer agents

Lemon Grass Essential Oil does not Modulate Cancer Cells Multidrug Resistance by Citral—Its Dominant and Strongly Antimicrobial Compound

With strong antimicrobial properties, citral has been repeatedly reported to be the dominant component of lemongrass essential oil. Here, we report on a comparison of the antimicrobial and anticancer activity of citral and lemongrass essential oil. The lemongrass essential oil was prepared by the vacuum distillation of fresh Cymbopogon leaves, with a yield of 0.5% (w/w). Citral content was measured by gas chromatography/high-resolution mass spectrometry (GC-HRMS) and determined to be 63%. Antimicrobial activity was tested by the broth dilution method, showing strong activity against all tested bacteria and fungi. Citral was up to 100 times more active than the lemongrass essential oil. Similarly, both citral and essential oils inhibited bacterial communication and adhesion during P. aeruginosa and S. aureus biofilm formation; however, the biofilm prevention activity of citral was significantly higher. Both the essential oil and citral disrupted the maturated P. aeruginosa biofilm with the IC50 7.3 ± 0.4 and 0.1 ± 0.01 mL/L, respectively. Although it may seem that the citral is the main biologically active compound of lemongrass essential oil and the accompanying components have instead antagonistic effects, we determined that the lemongrass essential oil-sensitized methicillin-resistant S. aureus (MRSA) and doxorubicin-resistant ovarian carcinoma cells and that this activity was not caused by citral. A 1 mL/L dose of oil-sensitized MRSA to methicillin up to 9.6 times and a dose of 10 µL/L-sensitized ovarian carcinoma to doxorubicin up to 1.8 times. The mode of multidrug resistance modulation could be due to P-glycoprotein efflux pump inhibition. Therefore, the natural mixture of compounds present in the lemongrass essential oil provides beneficial effects and its direct use may be preferred to its use as a template for citral isolation

Selectively Halogenated Flavonolignans—Preparation and Antibacterial Activity

A library of previously unknown halogenated derivatives of flavonolignans (silybins A and B, 2,3-dehydrosilybin, silychristin A, and 2,3-dehydrosilychristin A) was prepared. The effect of halogenation on the biological activity of flavonolignans was investigated. Halogenated derivatives had a significant effect on bacteria. All prepared derivatives inhibited the AI-2 type of bacterial communication (quorum sensing) at concentrations below 10 µM. All prepared compounds also inhibited the adhesion of bacteria (Staphyloccocus aureus and Pseudomonas aeruginosa) to the surface, preventing biofilm formation. These two effects indicate that the halogenated derivatives are promising antibacterial agents. Moreover, these derivatives acted synergistically with antibiotics and reduced the viability of antibiotic-resistant S. aureus. Some flavonolignans were able to reverse the resistant phenotype to a sensitive one, implying that they modulate antibiotic resistance