In vitro activity and mode of action of phenolic compounds on Leishmania donovani

Essential oil of Origanum species is well known for antimicrobial activity, but only a few have been evaluated in narrow spectrum antiprotozoal assays. Herein, we assessed the antiprotozoal potential of Turkish Origanum onites L. oil and its major constituents against a panel of parasitic protozoa. The essential oil was obtained by hydrodistillation from the dried herbal parts of O. onites and analyzed by Gas Chromatography-Flame Ionization Detector (GC-FID) and Gas Chromatography coupled with Mass Spectrometry (GC-MS). The in vitro activity of the oil and its major components were evaluated against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. The main component of the oil was identified as carvacrol (70.6%), followed by linalool (9.7%), p-cymene (7%), γ-terpinene (2.1%), and thymol (1.8%). The oil showed significant in vitro activity against T. b. rhodesiense (IC50 180 ng/mL), and moderate antileishmanial and antiplasmodial effects, without toxicity to mammalian cells. Carvacrol, thymol, and 10 additional abundant oil constituents were tested against the same panel; carvacrol and thymol retained the oil’s in vitro antiparasitic potency. In the T. b. brucei mouse model, thymol, but not carvacrol, extended the mean survival of animals. This study indicates the potential of the essential oil of O. onites and its constituents in the treatment of protozoal infections.

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Anti-Legionella Activity of Essential Oil of Satureja cuneifolia

Natural Product Communications ◽

10.1177/1934578x1400900534 ◽

2014 ◽

Vol 9 (5) ◽

pp. 1934578X1400900

Author(s):

Valerija Dunkić ◽

Antonija Mikrut ◽

Nada Bezić

Keyword(s):

Phenolic Compounds ◽

Essential Oil ◽

Vitro Activity ◽

In Vitro Activity ◽

High Concentration ◽

Different Sources

The essential oil of Satureja cuneifolia Ten. was characterized by a high concentration of the phenolic compounds carvacrol (21.3%) and thymol (9.2%). The in vitro activity of the essential oil against Legionela pneumophila serogroups (SG) 1 and 2-15 and Legionella spp. from different sources, using micro-dilution, showed that L. pneumofila is sensitive to the oil, with MICs ranging from 0.12 to 0.5%, v/v, and a MBC at 0.5 to 1%, v/v. The essential oil of S. cuneifolia was effective in the reduction of Legionellosis infections.

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In vitro activity and mode of action of fluoroquinolones

Pharmaceutisch Weekblad Scientific Edition ◽

10.1007/bf02075251 ◽

1987 ◽

Vol 9 (S1) ◽

pp. S2-S10

Author(s):

L. Verbist

Keyword(s):

Mode Of Action ◽

Vitro Activity ◽

In Vitro Activity

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In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkp500 ◽

2010 ◽

Vol 65 (3) ◽

pp. 508-511 ◽

Cited By ~ 83

Author(s):

K. Seifert ◽

P. Escobar ◽

S. L. Croft

Keyword(s):

Host Cell ◽

Leishmania Donovani ◽

Vitro Activity ◽

In Vitro Activity

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In vitro activity of rifabutin against 293 contemporary carbapenem-resistant Acinetobacter baumannii clinical isolates and characterization of rifabutin mode of action and resistance mechanisms

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa370 ◽

2020 ◽

Vol 75 (12) ◽

pp. 3552-3562

Author(s):

Vincent Trebosc ◽

Birgit Schellhorn ◽

Julian Schill ◽

Valentina Lucchini ◽

Jacqueline Bühler ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Mode Of Action ◽

Resistance Mechanisms ◽

Vitro Activity ◽

Clinical Isolates ◽

Oral Drug ◽

In Vitro Activity ◽

Carbapenem Resistant ◽

The Usa

Abstract Background Rifabutin, an oral drug approved to treat Mycobacterium avium infections, demonstrated potent activity against Acinetobacter baumannii in nutrient-limited medium enabled by rifabutin cellular uptake through the siderophore receptor FhuE. Objectives To determine rifabutin in vitro activity and resistance mechanisms in a large panel of A. baumannii isolates. Methods Two hundred and ninety-three carbapenem-resistant A. baumannii clinical isolates collected from Europe, the USA and Asia during 2017–19 were used for MIC determination. Sequencing/genotyping of fhuE, rpoB and arr-2 genes in isolates with elevated rifabutin MIC combined with genetic engineering and gene expression quantification was used to characterize rifabutin’s mode of action and resistance mechanisms. Results Rifabutin showed excellent activity on the strain panel, with an MIC50/90 of 0.008/1 mg/L, and was superior to all other antibiotics tested, including colistin, tigecycline and cefiderocol (MIC90 of 8 mg/L). Rifabutin remained active on resistant subpopulations, including strains resistant to the siderophore–drug conjugate cefiderocol (MIC90 of 2 mg/L, n = 23). At least two independent resistance mechanisms were required to abolish rifabutin activity, which is in line with the dose-dependent mutational resistance frequency reaching 10−9 at rifabutin concentrations at or above 2 mg/L. Conclusions This study demonstrated the potent activity of rifabutin against carbapenem-resistant A. baumannii. We propose that FhuE-mediated active uptake of rifabutin enables activity against rifampicin-resistant isolates. To achieve clinically meaningful strain coverage and to avoid rapid resistance development, rifabutin concentrations ≥2 mg/L are required, something rifabutin oral formulations cannot deliver.

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