UV-B-induced synthesis of mycosporine-like amino acids in three strains of Nodularia (cyanobacteria)

Three filamentous and heterocystous cyanobacterial strains of Nodularia, Nodularia baltica, Nodularia harveyana and Nodularia spumigena, have been tested for the presence and induction of ultraviolet-absorbing/screening mycosporine-like amino acids (MAAs) by simulated solar radiation in combination with 395 (receiving photosynthetically active radiation (PAR) only), 320 (receiving PAR + UV-A) and 295 (receiving PAR + UV-A + UV-B) nm cut-off filters. Absorption spectroscopic analyses of the methanolic extracts of samples revealed a typical MAA peak at 334 nm in all three cyanobacteria. Specific contents of MAAs had a pronounced induction in the samples covered with 295 nm cut-off filters after 72 h of irradiation. In comparison, there was little induction of MAAs in the samples covered by 395 and 320 nm cut-off filters. High performance liquid chromatographic (HPLC) studies revealed the presence of two types of MAAs in all three cyanobacteria, which were identified as shinorine and porphyra-334, both absorbing maximally at 334 nm. The occurrence of porphyra-334 is rare in cyanobacteria. Specific content of both shinorine and porphyra-334 were induced remarkably only in the samples covered with 295 nm cut-off filters. The results indicate that in comparison to UV-A and PAR, UV-B is more effective in eliciting MAAs induction in the studied cyanobacteria.     

Palythine–threonine,a major novel mycosporine-like amino acid (MAA) isolated from the hermatypic coral Pocillopora capitata

Using a high-resolution reverse-phase liquid chromatography method we found that the tissues of the hermatypic coral Pocillopora capitata (collected in Santiago Bay, Mexico) contain a high diversity of primary and secondary mycosporine-like amino acids (MAAs) typical of some reef-building coral species: mycosporine–glycine, shinorine, porphyra-334, mycosporine–methylamine–serine, mycosporine–methylamine–threonine, palythine–serine, palythine and one additional novel predominant MAA, with an absorbance maximum of 320 nm. Here we document the isolation and characterization of this novel MAA from the coral P. capitata. Using low multi-stage mass analyses of deuterated and non deuterated compounds, high-resolution mass analyses (Time of Flight, TOF) and other techniques, this novel compound was characterized as palythine–threonine. Palythine–threonine was also present in high concentrations in the corals Pocillopora eydouxi and Stylophora pistillata indicating a wider distribution of this MAA among reef-building corals. From structural considerations we suggest that palythine–threonine is formed by decarboxylation of porphyra-334 followed by demethylation of mycosporine–methylamine–threonine.     

Photodegradation and photosensitization of mycosporine-like amino acids

The photodegradation and photosensitization of several mycosporine-like amino acids (MAAs) were investigated. The photodegradation of the MAA, palythine, was tested with three photosensitizers: riboflavin, rose bengal and natural seawater. For comparison of degradation rates, the riboflavin-mediated photosensitization of six other MAAs was also examined. When riboflavin was used as a photosensitizer in distilled water, MAAs were undetectable after 1.5h. Palythine showed little photodegradation when rose bengal was added as the photosensitizer (k=0.12x10(-3)m(2)kJ(-1)). Palythine dissolved in natural seawater containing high nitrate concentrations also showed slow photodegradation rate constants (k=0.26x10(-3)m(2)kJ(-1)) over a 24-h period of constant irradiation. Similar experiments in deep seawater with porphyra-334 and shinorine resulted in 75% of the initial MAA remaining after 4h of irradiation and rates of 0.018 and 0.026x10(-3) m(2) kJ(-1), respectively. Experiments conducted in deep seawater with riboflavin additions resulted in photodegradation rate constants between 0.77x10(-3) and 1.19x10(-3)m(2)kJ(-1) for shinorine and porphyra-334, respectively. Photoproduct formation appeared to be minimal with the presence of a dehydration product of the cycloheximine ring structure indicated as well as the presence of amino acids. Evidence continues to build for the role of MAAs as potent and stable UV absorbers. This study further highlights the photostability of several MAAs in both distilled and seawater in the presence of photosensitizers.     

Effect of light quality on the accumulation of photosynthetic pigments, proteins and mycosporine-like amino acids in the red alga Porphyra leucosticta (Bangiales, Rhodophyta)

The effect of different light qualities (white, blue, green, yellow and red light) on photosynthesis, measured as chlorophyll fluorescence, and the accumulation of photosynthetic pigments, proteins and the UV-absorbing mycosporine-like amino acids (MAAs) was studied in the red alga Porphyra leucosticta. Blue light promoted the highest accumulation of nitrogen metabolism derived compounds i.e., MAAs, phycoerythrin and proteins in previously N-starved algae after seven days culture in ammonium enriched medium. Similar results were observed in the culture under white light. In contrast, the lowest photosynthetic capacity i.e., lowest electron transport rate and lowest photosynthetic efficiency as well as the growth rate were found under blue light, while higher values were found in red and white lights. Blue light favored the accumulation of the MAAs porphyra-334, palythine and asterina-330 in P. leucosticta. However, white, green, yellow and red lights favored the accumulation of shinorine. The increase of porphyra-334, palythine and asterina-330 occurred in blue light simultaneous to a decrease in shinorine. The accumulation of MAAs and other nitrogenous compounds in P. leucosticta under blue light could not be attributed to photosynthesis and the action of a non-photosynthetic blue light photoreceptor is suggested. A non-photosynthetic photoreceptor could be also involved in the MAAs interconversion pathways in P. leucosticta.     

Biotransformation of mycosporine like amino acids (MAAs) in the toxic dinoflagellate Alexandrium tamarense

Changes in mycosporine-like amino acids (MAAs) induced by the increase of photosynthetically active radiation (PAR) were studied in the toxic dinoflagellate Alexandrium tamarense. Cultures of A. tamarense were maintained at exponential growth under low (25 micromol quanta m(-2)s(-1)) PAR irradiance. The cultures were nutrient enriched and one day later exposed to higher irradiance (150 micromol quanta m(-2)s(-1)). The content of MAAs was determined by means of high performance liquid chromatography (HPLC). Eleven MAAs, including some partially characterized compounds, were identified. The MAAs synthesis induction can be described as a two-stage process. The first one involves the net synthesis of the MAAs bi-substituted by amino acids. In the second stage these compounds were transformed into other secondary MAAs. The two most prominent changes were observed in the concentration of porphyra-334 and palythene. The cellular concentration of porphyra-334 increased during the first 2h of exposure to higher irradiance and then decreased rapidly. In contrast, the cellular concentration of palythene showed a continuous accumulation since the beginning of the exposure. In A. tamarense the main route of MAAs transformation has porphyra-334 as a precursor of a sequential conversion resulting in the accumulation of palythene.     

Can Mycosporine‐Like Amino Acids Act as Multifunctional Compounds in Gymnodinium catenatum (Dinophyceae)?

MAAs originating from Gymnodinium catenatum were subjected to H₂O₂ oxidation, light and heat. Shinorine and porphyra‐334 were the more resistant to all treatments, mycosporine‐glycine (MYGL) was the least resistant to oxidation and heat, whereas palythene and M‐370 were the least resistant to light. MYGL and M‐311 were similarly resistant to photodegradation and oxidation in the dark and low temperature, but M‐311 was more resistant to oxidation under light or heat. The ratio M‐370/M‐365 changed from 29:1 to 6:1 ratio after 240 h of exposure to fluorescent light, indicating that M‐365 could represent the M‐370 cis‐isomer. The role of MAAs as antioxidants and/or osmolytes was evaluated by studying effects of abrupt salinity reduction. Both increases or decreases in concentrations were observed and were dependent on the MAA initial concentration and its chemical structure. The relative increase in MAAs with a known antioxidant capacity (MYGL, palythene) followed an exponential decay trend related to initial concentration. The relative decrease in highly polar MAAs (shinorine, porphyra‐334, M‐332) with a suspected osmolyte role followed a rise to a maximum with the increase in initial concentration. Whether or not MAAs play a significant role in osmoregulation, their loss can occur upon hypoosmotic shock.     

Effects of short-term irradiation on photoinhibition and accumulation of mycosporine-like amino acids in sun and shade species of the red algal genus Porphyra

The effect of irradiance (40 and 840 micromol photons m(-2) s(-1)) of short-term (48 h) irradiation on photosynthetic activity (estimated as oxygen evolution and as chlorophyll fluorescence), specific absorption and fluorescence excitation spectra, photosynthetic pigment accumulation (chlorophyll a and biliproteins) and UV-absorbing compounds (mycosporine-like amino acids, MAAs) was investigated in sun and shade species of the red algal genus Porphyra collected in Trondheimsfjord (Norway). In the sun type, high irradiance exposure (840 micromol photons m(-2) s(-1)) did not alter the Chl a concentration, however, exposure to a lower irradiance (40 micromol photons m(-2) s(-1)) for 48 h significantly increased the chlorophyll concentration. The content of MAAs was significantly higher in the suntype than in the shade type algae. Porphyra-334 is the main MAA in this species followed by shinorine. The total content of MAAs significantly (P<0.05) increased in the sun type after 48 h exposure to both high and low irradiances. However, in the shade type, porphyra-334 significantly decreased (P<0.05) after both high and low irradiance exposure. Photosynthetic activity (as oxygen evolution) and the optimal quantum yield (F(v)/F(m)), as an indicator of photoinhibition, decreased under low and high irradiance in the shade type algae and no full recovery was observed when the algae were transferred to very low irradiation.The sun type algae presented a higher capacity of acclimation to increased irradiance than the shade type algae. This high acclimation of sun type algae to short term high irradiance exposure (48 h) is explained by the higher thermal dissipation. This was estimated as the ratio of nonphotochemical quenching related to the light dose (q(N):dose) and by the accumulation of MAAs.     

Effect of UV-B Radiation and Desiccation Stress on Photoprotective Compounds Accumulation in Marine <Emphasis Type="Italic">Leptolyngbya</Emphasis> sp.

Increased awareness regarding the harmful effects of ultraviolet (UV)-B radiation has led to the search for new sources of natural UV-B protecting compounds. Mycosporine-like amino acids are one of such promising compounds found in several organisms. Cyanobacteria are ideal organisms for isolation of these compounds due to their compatibility and adaptability to thrive under harsh environmental conditions. In the following investigation, we report the production of shinorine in Leptolyngbya sp. isolated from the intertidal region. Based on the spectral characteristics and liquid chromatography-mass spectrometry analysis, the UV-absorbing compound was identified as shinorine. To the best of our knowledge, this is the first report on the occurrence of shinorine in Leptolyngbya sp. We also investigated the effect of artificial UV-B radiation and periodic desiccation on chlorophyll-a, total carotenoids, and mycosporine-like amino acids (MAAs) production. The UV-B radiation had a negative effect on growth and chlorophyll concentration, whereas it showed an inductive effect on the production of total carotenoids and MAAs. Desiccation along with UV-B radiation led to an increase in the concentration of photoprotective compounds. These results indicate that carotenoids and MAAs thus facilitate cyanobacteria to avoid and protect themselves from the deleterious effects of UV-B and desiccation.     

Structural Characterization of Cis– and Trans–Pt(NH3)2Cl2 Conjugations with Chitosan Nanoparticles

The conjugation of chitosan 15 and 100 KD with anticancer drugs cis– and trans–Pt (NH₃)₂Cl₂ (abbreviated cis–Pt and trans–Pt) were studied at pH 5–6. Using multiple spectroscopic methods and thermodynamic analysis to characterize the nature of drug–chitosan interactions and the potential application of chitosan nanoparticles in drug delivery. Analysis showed that both hydrophobic and hydrophilic contacts are involved in drug–polymer interactions, while chitosan size and charge play a major role in the stability of drug–polymer complexes. The overall binding constants are K_{ch–15–cis–Pt} = 1.44 (±0.6) × 10⁵ M⁻¹, K_{ch–100–cis–Pt} = 1.89 (±0.9) × 10⁵ M⁻¹ and K_{ch–15–trans–Pt} = 9.84 (±0.5) × 10⁴ M⁻¹, and K_{ch–100–trans–Pt} = 1.15 (±0.6) × 10⁵ M⁻¹. More stable complexes were formed with cis–Pt than with trans–Pt–chitosan adducts, while stronger binding was observed for chitosan 100 in comparison to chitosan 15 KD. This study indicates that polymer chitosan 100 is a stronger drug carrier than chitosan 15 KD in vitro.     

Novel glycosylated mycosporine-like amino acids with radical scavenging activity from the cyanobacterium Nostoc commune

Mycosporine-like amino acids (MAAs) are UV absorbing pigments, and structurally distinct MAAs have been identified in taxonomically diverse organisms. Two novel MAAs were purified from the cyanobacterium Nostoc commune, and their chemical structures were characterized. An MAA with an absorption maximum at 335 nm was identified as a pentose-bound porphyra-334 derivative with a molecular mass of 478 Da. Another identified MAA had double absorption maxima at 312 and 340 nm and a molecular mass of 1,050 Da. Its unique structure consisted of two distinct chromophores of 3-aminocyclohexen-1-one and 1,3-diaminocyclohexen and two pentose and hexose sugars. These MAAs had radical scavenging activity in vitro; the 1050-Da MAA contributed approximately 27% of the total radical scavenging activities in a water extract of N. commune. These results suggest that these glycosylated MAAs have multiple roles as a UV protectant and an antioxidant relevant to anhydrobiosis in N. commune.     

Sulfur Deficiency Changes Mycosporine-like Amino Acid (MAA) Composition of Anabaena variabilis PCC 7937: A Possible Role of Sulfur in MAA Bioconversion

In the present investigation we show for the first time that bioconversion of a primary mycosporine-like amino acid (MAA) into a secondary MAA is regulated by sulfur deficiency in the cyanobacterium Anabaena variabilis PCC 7937. This cyanobacterium synthesizes the primary MAA shinorine (RT = 2.2 min, λ_max = 334 nm) under normal conditions (PAR + UV-A + UV-B); however, under sulfur deficiency, a secondary MAA palythine-serine (RT = 3.9 min, λ_max = 320 nm) appears. Addition of methionine to sulfur-deficient cultures resulted in the disappearance of palythine-serine, suggesting the role of primary MAAs under sulfur deficiency in recycling of methionine by donating the methyl group from the glycine subunit of shinorine to tetrahydrofolate to regenerate the methionine from homocysteine. This is also the first report for the synthesis of palythine-serine by cyanobacteria which has so far been reported only from corals. Addition of methionine also affected the conversion of mycosporine-glycine into shinorine, consequently, resulted in the appearance of mycosporine-glycine (RT = 3.6 min, λ_max = 310 nm). Our results also suggest that palythine-serine is synthesized from shinorine. Based on these results we propose that glycine decarboxylase is the potential enzyme that catalyzes the bioconversion of shinorine to palythine-serine by decarboxylation and demethylation of the glycine unit of shinorine.     

Aphanorphine,a novel tricyclic alkaloid from the blue-green algaAphanizomenon flos-aquae

An alkaloid with a benzazepine skeleton, aphanorphine (1) was isolated from the blue-green alga, Aphanizomenon flos-aquae together with its previously known constituents neosaxitoxin and saxitoxin.     

Demonstration of Allium sativum Extract Inhibitory Effect on Biodeteriogenic Microbial Strain Growth,Biofilm Development,and Enzymatic and Organic Acid Production

To the best of our knowledge, this is the first study demonstrating the efficiency of Allium sativum hydro-alcoholic extract (ASE) againstFigure growth, biofilm development, and soluble factor production of more than 200 biodeteriogenic microbial strains isolated from cultural heritage objects and buildings. The plant extract composition and antioxidant activities were determined spectrophotometrically and by HPLC–MS. The bioevaluation consisted of the qualitative (adapted diffusion method) and the quantitative evaluation of the inhibitory effect on planktonic growth (microdilution method), biofilm formation (violet crystal microtiter method), and production of microbial enzymes and organic acids. The garlic extract efficiency was correlated with microbial strain taxonomy and isolation source (the fungal strains isolated from paintings and paper and bacteria from wood, paper, and textiles were the most susceptible). The garlic extract contained thiosulfinate (307.66 ± 0.043 µM/g), flavonoids (64.33 ± 7.69 µg QE/g), and polyphenols (0.95 ± 0.011 mg GAE/g) as major compounds and demonstrated the highest efficiency against the Aspergillus versicolor (MIC 3.12–6.25 mg/mL), A. ochraceus (MIC: 3.12 mg/mL), Penicillium expansum (MIC 6.25–12.5 mg/mL), and A. niger (MIC 3.12–50 mg/mL) strains. The extract inhibited the adherence capacity (IIBG% 95.08–44.62%) and the production of cellulase, organic acids, and esterase. This eco-friendly solution shows promising potential for the conservation and safeguarding of tangible cultural heritage, successfully combating the biodeteriogenic microorganisms without undesirable side effects for the natural ecosystems.     

Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus,Vancomycin-Resistant Enterococcus faecium,and Permeabilized Gram-Negative Pathogens

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6–9) and machaeridiols A-C (10–12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, −1708, −1717, −33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6–8 and 10–12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC’s, compared to 12, against MRSA 1708 and −1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5–8 µg/mL for two strains of Acinetobacter baumannii, 2–16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae.     

Activity of Compounds from Temperate Propolis against Trypanosoma brucei and Leishmania mexicana

Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC₅₀ values < 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4′-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4′,7-dimethoxykaempferol, and naringenin 4′,7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities ≤ 15 µM. The most active compounds against T. brucei were naringenin 4′,7 dimethyl ether and 4′methoxy kaempferol with activity of 15–20 µM against the three T. brucei strains. The most active compounds against L. mexicana were 4′,7-dimethoxykaempferol and the coumaric acid ester mixture, with EC₅₀ values of 12.9 ± 3.7 µM and 13.1 ± 1.0 µM. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain; no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.     

Three Small Molecule Entities (MPK18, MPK334 and YAK308) with Activity against Haemonchus contortus In Vitro

Due to widespread multi-drug resistance in parasitic nematodes of livestock animals, there is an urgent need to discover new anthelmintics with distinct mechanisms of action. Extending previous work, here we screened a panel of 245 chemically-diverse small molecules for anti-parasitic activity against Haemonchus contortus—an economically important parasitic nematode of livestock. This panel was screened in vitro against exsheathed third-stage larvae (xL3) of H. contortus using an established phenotypic assay, and the potency of select compounds to inhibit larval motility and development assessed in dose-response assays. Of the 245 compounds screened, three—designated MPK18, MPK334 and YAK308—induced non-wildtype larval phenotypes and repeatedly inhibited xL3-motility, with IC₅₀ values of 45.2 µM, 17.1 µM and 52.7 µM, respectively; two also inhibited larval development, with IC₅₀ values of 12.3 µM (MPK334) and 6.5 µM (YAK308), and none of the three was toxic to human liver cells (HepG2). These findings suggest that these compounds deserve further evaluation as nematocidal candidates. Future work should focus on structure–activity relationship (SAR) studies of these chemical scaffolds, and assess the in vitro and in vivo efficacies and safety of optimised compounds against adults of H. contortus.     

Antibacterial Thiopeptide GE2270-Congeners from Nonomuraea jiangxiensis

Thiopeptides are macrocyclic natural products with potent bioactivity. Nine new natural thiopeptides (1–9) were obtained from a Nonomuraea jiangxiensis isolated from a terrestrial soil sample collected in Singapore. Even though some of these compounds were previously synthesized or isolated from engineered strains, herein we report the unprecedented isolation of these thiopeptides from a native Nonomuraea jiangxiensis. A comparison with the literature and a detailed analysis of the NMR and HRMS of compounds 1–9 was conducted to assign their chemical structures. The structures of all new compounds were highly related to the thiopeptide antibiotics GE2270, with variations in the substituents on the thiazole and amino acid moieties. Thiopeptides 1–9 exhibited a potent antimicrobial activity against the Gram-positive bacteria, Staphylococcus aureus with MIC₉₀ values ranging from 2 µM to 11 µM. In addition, all compounds were investigated for their cytotoxicity against the human cancer cell line A549, none of the compounds were cytotoxic.     

In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense

This study reports the isolation of three new C₂₀ diterpenoid alkaloids, Chitralinine A–C (1–3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1–3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC₅₀ value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol⁻¹ for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease.     

Chemical Analysis and In Vitro Bioactivity of Essential Oil of Laurelia sempervirens and Safrole Derivatives against Oomycete Fish Pathogens

In this study, the essential oil (EO) from Laurelia sempervirens was analyzed by GC/MS and safrole (1) was identified as the major metabolite 1, was subjected to direct reactions on the oxygenated groups in the aromatic ring and in the side chain, and eight compounds (4 to 12) were obtained by the process. EO and compounds 4–12 were subjected to biological assays on 24 strains of the genus Saprolegnia, specifically of the species 12 S. parasitica and 12 S. australis. EO showed a significant effect against Saprolegnia strains. Compound 6 presents the highest activity against two resistant strains, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 25 to 100 and 75 to 125 µg/mL, respectively. The results show that compound 6 exhibited superior activities compared to the commercial controls bronopol and azoxystrobin used to combat these pathogens.     

Antifungal Activity of Lavandula angustifolia Essential Oil against Candida albicans: Time-Kill Study on Pediatric Sputum Isolates

The aim of our study was to determine the susceptibility of 15 Candida albicans sputum isolates on fluconazole and caspofungin, as well as the antifungal potential of Lavandula angustifolia essential oil (LAEO). The commercial LAEO was analyzed using gas chromatography-mass spectrometry. The antifungal activity was evaluated using EUCAST protocol. A killing assay was performed to evaluate kinetics of 2% LAEO within 30 min treatment. LAEO with major constituents’ linalool (33.4%) and linalyl acetate (30.5%) effective inhibited grows of C. albicans in concentration range 0.5–2%. Fluconazole activity was noted in 67% of the isolates with MICs in range 0.06–1 µg/mL. Surprisingly, 40% of isolates were non-wild-type (non-WT), while MICs for WT ranged between 0.125–0.25 µg/mL. There were no significant differences in the LAEO MICs among fluconazole-resistant and fluconazole-susceptible sputum strains (p = 0.31) and neither among caspofungin non-WT and WT isolates (p = 0.79). The 2% LAEO rapidly achieved 50% growth reduction in all tested strains between 0.2 and 3.5 min. Within 30 min, the same LAEO concentration exhibited a 99.9% reduction in 27% isolates. This study demonstrated that 2% solution of LAEO showed a significant antifungal activity which is equally effective against fluconazole and caspofungin susceptible and less-susceptible strains.