UHPLC-MS/MS and GC-MS Metabolic Profiling of a Medicinal Flourensia Fiebrigii Chemotype.

The comparative metabolic profiling and their biological properties of eight extracts obtained from diverse parts (leaves, flowers, roots) of the medicinal plant Flourensia fiebrigii S.F. Blake, a chemotype growing in highland areas (2750 m a.s.l.) of northwest Argentina, were investigated. The extracts were analysed by GC-MS and UHPLC-MS/MS. GC-MS analysis revealed the presence of encecalin (relative content: 24.86 %) in ethereal flower extract (EF) and this benzopyran (5.93 %) together sitosterol (11.35 %) in the bioactive ethereal leaf exudate (ELE). By UHPLC-MS/MS the main compounds identified in both samples were: limocitrin, (22.31 %), (2Z)-4,6-dihydroxy-2-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-1-benzofuran-3-one (21.31 %), isobavachin (14.47 %), naringenin (13.50 %), and sternbin, (12.49 %). Phytocomplexes derived from aerial parts exhibited significant activity against biofilm production of Pseudomonas aeruginosa and Staphylococcus aureus, reaching inhibitions of 74.7-99.9 % with ELE (50 µg/mL). Notably, the extracts did not affect nutraceutical and environmental bacteria, suggesting a selective activity. ELE also showed the highest reactive species scavenging ability. This study provides valuable insights into the potential applications of this chemotype.

Citrus sinensis Essential Oils an Innovative Antioxidant and Antipathogenic Dual Strategy in Food Preservation against Spoliage Bacteria.

The present study evaluates the chemical compositions and antioxidant and antipathogenic properties of commercial orange (Citrus sinensis (L.) Osbeck) essential oils obtained using the cold-press method (EOP) and the cold-press method followed by steam distillation (EOPD). The chemical compositions of the volatilizable fractions, determined by gas chromatography-mass spectrometry, were similar in both samples. A relatively large amount of γ-terpinene was found in the EOPD (1.75%) as compared to the EOP (0.84%). Monoterpene hydrocarbons with limonene (90.4-89.8%) followed by myrcene (3.2-3.1%) as the main compounds comprised the principal phytochemical group. The non-volatile phenolics were eight times higher in the EOP than in the EOPD. Several assays with different specificity levels were used to study the antioxidant activity. Although both essential oils presented similar reducing capacities, the radical elimination ability was higher for the EOP. Regarding the antipathogenic properties, the EOs inhibited the biomass and cell viability of Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Furthermore, both EOs similarly attenuated the production of elastase, pyocyanin, and quorum-sensing autoinducers as assessed using Gram-negative bacteria. The EOP and EOPD showed important antioxidant and antipathogenic properties, so they could represent natural alternatives to extend the shelf life of food products by preventing oxidation and contamination caused by microbial spoilage.

Home parenteral nutrition in older vs younger patients: Clinical characteristics and outcomes.

BACKGROUND: There is a demographic shift toward older patients receiving home parenteral nutrition (HPN), but data on clinical outcomes are limited. The objective of this study was to determine differences between older and younger HPN patients in regard to HPN indications, prescriptions, and outcomes over the first 2 years receiving HPN. METHODS: This was a retrospective analysis of prospectively collected data from HPN adult patients entered in the Canadian HPN Registry. New HPN patients enrolled between 2003 and 2017 and receiving HPN for at least 2 years were selected. Data included demographics, PN prescriptions, catheter-related bloodstream infections (CRBSIs) over the past year, survival, and quality of life based on Karnofsky Performance Status (KPS). RESULTS: Four hundred two patients were included: 184 patients were ≥60 years old, and 219 patients were between 18 and 59 years old. There were no differences in the main indications for HPN, body mass index (BMI), and PN prescriptions at baseline. At 2 years, younger patients received more energy from PN than older patients (27.9 vs 19.6 kcal/kg; P < .001), but BMI remained comparable. There were fewer CRBSIs in the older group (20% vs 36%, P = .0023), but 78% of younger patients remained alive vs 69% in the older group (P = .0401). In those alive, the proportion of patients continuing to receive HPN was comparable and the proportion of patients with a KPS ≥60. CONCLUSIONS: Older HPN patients have similar clinical characteristics as younger patients but have fewer CRBSIs and higher 2-year mortality.

Is the risk of refeeding syndrome a problem in reaching nutritional requirements? A cohort of patients on enteral nutrition support.

INTRODUCTION: Background: refeeding syndrome (RS) is a metabolic complication associated with nutritional support. The lack of management protocols for patients on nutritional support may lead to the development of RS or undernourishment. Objective: to evaluate adherence to the algorithm for total enteral nutritional support (ASNET), and the efficacy of reaching nutrient requirements in patients at risk of RS. Methods: a cohort study: screening and nutritional evaluation of patients and risk of RS were performed. Adults admitted to hospital for noncritical illness who received exclusively enteral nutrition (EN) were eligible. Patients with RS, intestinal failure or chronic diarrhea were excluded. Adherence to ASNET was evaluated along with the efficacy of nutritional support to reach the optimal protein and energy requirement (OPER) and any associated complications. Patient follow-up ended when the feeding route was changed or upon discharge. Results: a total of 73 patients were included (mean age, 62 ± 16 yrs; BMI, 18.5 ± 4.2 kg/m2), and 55 % were men. All had nutritional risk of developing RS (57, low; 15, high; 1, very high); 34 % had adequate adherence to ASNET, and 33 % managed to cover the total requirement between 4 and 6 days. OPER was reached by 38 % by the fourth day of EN, and adequate adherence to ASNET increased the probability of achieving it (RR, 2.2; 95 % CI, 1.6-3.2, p < 0.0001) without increasing the associated complications. Nonetheless, 36 % developed complications, of whom 96 % did not adhere to ASNET. Conclusion: adherence to ASNET in patients at risk of RS allowed the achievement of OPER safely by day four with fewer associated complications.

INTRODUCCIÓN: Antecedentes: el síndrome de realimentación (SR) es una complicación metabólica asociada al soporte nutricional y la falta de protocolos puede conducir a su desarrollo o a desnutrición. Objetivo: evaluar la adherencia al algoritmo de soporte nutricional enteral total (ASNET) y la eficacia de alcanzar los requisitos de nutrientes en pacientes con riesgo de SR. Métodos: se realizó un estudio de cohortes con evaluación nutricional del paciente y del riesgo de SR. Fueron elegibles los adultos ingresados en el hospital por una enfermedad no crítica que recibían exclusivamente nutrición enteral (NE). Se excluyeron los pacientes con SR, falla intestinal o diarrea crónica. Se evaluaron la adherencia al ASNET y la eficacia para alcanzar el requerimiento óptimo de proteína, energía (OPER) y cualquier complicación asociada. El seguimiento finalizó cuando se cambió la ruta de alimentación o al alta. Resultados: se incluyeron 73 pacientes (edad de 62 ± 16 años, IMC de 18,5 ± 4,2 kg/m2) y el 55 % fueron hombres. Todos tenían riesgo nutricional de desarrollar SR (57 bajo; 15 alto; 1 muy alto). El 34 % presentaron una adherencia adecuada y el 33 % lograron cubrir el requerimiento total entre 4 y 6 días. La OPER se alcanzó en el 38 % al cuarto día de NE, y la adecuada adherencia al ASNET aumentó la probabilidad de lograrla (RR: 2.2; IC 95 %: 1,6-3,2, p < 0,0001) sin incrementar las complicaciones asociadas. No obstante, el 36 % desarrollaron complicaciones y el 96 % de estos casos no se habían adherido al ASNET. Conclusión: la adherencia al ASNET en los pacientes con riesgo de SR permitió lograr la OPER de forma segura al cuarto día y con menos complicaciones asociadas.

Lemon Oils Attenuate the Pathogenicity of Pseudomonas aeruginosa by Quorum Sensing Inhibition.

The chemical composition of three Citrus limon oils: lemon essential oil (LEO), lemon terpenes (LT) and lemon essence (LE), and their influence in the virulence factors production and motility (swarming and swimming) of two Pseudomonas aeruginosa strains (ATCC 27853 and a multidrug-resistant HT5) were investigated. The main compound, limonene, was also tested in biological assays. Eighty-four compounds, accounting for a relative peak area of 99.23%, 98.58% and 99.64%, were identified by GC/MS. Limonene (59-60%), γ-terpinene (10-11%) and ß-pinene (7-15%) were the main compounds. All lemon oils inhibited specific biofilm production and bacterial metabolic activities into biofilm in a dose-dependent manner (20-65%, in the range of 0.1-4 mg mL-1) of both strains. Besides, all samples inhibited about 50% of the elastase activity at 0.1 mg mL-1. Pyocyanin biosynthesis decreases until 64% (0.1-4 mg mL-1) for both strains. Swarming motility of P. aeruginosa ATCC 27853 was completely inhibited by 2 mg mL-1 of lemon oils. Furthermore, a decrease (29-55%, 0.1-4 mg mL-1) in the synthesis of Quorum sensing (QS) signals was observed. The oils showed higher biological activities than limonene. Hence, their ability to control the biofilm of P. aeruginosa and reduce the production of virulence factors regulated by QS makes lemon oils good candidates to be applied as preservatives in the food processing industry.

Lipophilic 9,10-Dehydrofukinone Action on Pathogenic and Non-Pathogenic Bacterial Biofilms. Why Is This Main Volatile Metabolite in Senecio?

The effect of a natural sesquiterpene ketone, 9,10-dehydrofukinone (DHF), on pathogenic Staphylococcus aureus and Pseudomonas aeruginosa strains isolated from chronic infectious processes, was the focus of the present study. Lipophilic DHF produced important antibacterial synergistic effects in association with ciprofloxacin (CPX) against two biofilm-forming strains of S. aureus HT1 (FIC=0.21) and P. aeruginosa HT5 (FIC=0.05). Hence, this mixture constitutes an excellent strategy to combat these biofilm-producing bacteria that overexpress drug efflux pumps as a resistance mechanism. Additionally, a substantial rise in beneficial Lactobacillus biofilm biomass was determined as a very significant finding of this association. Particularly, a non-pathogenic biofilm increment of 119 % was quantified when the mixture was added to a probiotic L. acidophilus ATCC SD-5212 culture. A surface activity enhanced in 71 % with respect to untreated L. acidophilus culture was also generated by the DHF and CPX association, and therefore, a glycoprotein synthesis induction mediated by the mixture is discussed. The results obtained could help in the development of new selective antibiotics. From an ecological standpoint, the present study strongly suggests that DHF is a polyfunctional organic molecule produced with a high yield in Senecio punae that exerts a positive impact on a non-pathogenic plant bacterium L. plantarum CE105.

Grapefruit essential oils inhibit quorum sensing of Pseudomonas aeruginosa.

Citrus essential oils are used in food to confer flavor and aromas. The citrus essential oils have been granted as GRAS and could be used as antimicrobial additives to control bacterial quorum sensing from potential food bacterial pathogens. The chemical composition and inhibitory activity of Citrus paradisi (grapefruit) essential oils obtained by cold-pressed method (EOP) and cold-pressed method followed by steam distillation, against Pseudomonas aeruginosa were determined. The GC-MS analyses of the oil indicated the amount of the essential oil components was highest with D-limonene in both cases. However, the extraction method modified the chemical composition. EOP had higher amount of coumarins and flavonoid as well as less oxygenated terpenoids. At 0.1 mg/mL essential oils were not able to modify the bacterial development but inhibited the P. aeruginosa biofilm production between 52% and 55%, sessile viability between 45% and 48%, autoinducer production and elastase activity between 30% and 56%. Limonene was less effective at inhibiting P. aeruginosa than the essential oils, suggesting a synergistic effect of the minor components. According to our results, grapefruit essential oils could be used as a food preservative to control P. aeruginosa virulence.

Effect of Wine Wastes Extracts on the Viability and Biofilm Formation of Pseudomonas aeruginosa and Staphylococcus aureus Strains.

In this work, we intended to inhibit the biofilm synthesis and the metabolism of Gram-positive and Gram-negative bacteria using two highly available wastes (stem and marc) obtained after the manufacturing of Torrontes wine at Cafayate, Argentina. Wine wastes contain a significant amount of bioactive compounds, mainly phenolic compounds, which makes them a potential source of compounds with beneficial properties to human health, as they could inhibit the virulence of pathogenic bacteria or protect the tissue against oxidative stress. Marc and stem extracts of Torrontes wine were evaluated for their ability to inhibit the metabolism and biofilm production of Pseudomonas aeruginosa and Staphylococcus aureus strains. The phytochemical composition and antioxidant activity of these extracts were also determined. The methanol and ethyl acetate extracts, which contained the highest amount of total polyphenolic, exhibited the highest scavenging capacity of ABTS and nitric oxide and the strongest Fe3+ reducing power and exhibited the highest level of inhibition of the biofilm formation and of the metabolic activity in bacterial biofilm. We also noticed a positive correlation between phenolic compounds content, the antioxidant activity, and the anti-biofilm capacity of the winemaking wastes. These results display the potentiality of wine wastes to prevent or reduce the formation of biofilm. Moreover, their abundance makes them an attractive and affordable source of antibiofilm and antioxidant agents.

Blastic Transformation in Mexican Population With Chronic Myelomonocytic Leukemia.

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is the most aggressive of chronic leukemias, with short overall survival and a high transformation rate to acute leukemia. We investigated the factors related to blastic transformation in a Mexican population treated at a tertiary referral center. PATIENTS AND METHODS: The records of patients with a diagnosis of CMML from 2000 to 2015 were reviewed. A total of 54 patients were included, with a median age of 71 years and an overall survival of 16 months. The patients with incomplete data were excluded. IBM SPSS Statistics, version 21.0, software was used to perform the statistical analysis. RESULTS: The rate of blastic transformation was 33% (18 patients), and the interval time to progression was 9 months (range, 0-87 months). Comparing the patients who did not undergo blastic transformation to those who did, those with progression to acute leukemia tended to be younger (age, 58 vs. 71 years; P = .001), to have a greater peripheral blood blast count (≥ 2% vs. 0%; P = .003), and were more likely to have immature myeloid precursors circulating in the peripheral blood (94% vs. 64%; P = .02). On multivariate analysis, younger age continued to be a statistically significant factor for progression (hazard ratio, 0.97; 95% confidence interval, 0.929-0.987). CONCLUSION: Mexican patients with CMML that progressed to overt acute leukemia were considerably younger, with a higher tumor burden and short overall survival. In this population, it is important to consider more aggressive treatment at diagnosis, focusing on high-dose chemotherapy and hematopoietic stem cell transplantation within a short period.

A New Depigmenting-Antifungal Methylated Grindelane from Grindelia chiloensis.

The new methylated grindelane diterpenoid, 7ß-hydroxy-8(17)-dehydrogrindelic acid (1b), together with the known 7α-hydroxy-8(17)-dehydrogrindelic acid (2a), 6-oxogrindelic acid (3a), 4ß-hydroxy-6-oxo-19-norgrindelic (4a), 19-hydroxygrindelic acid (5a), 18-hydroxygrindelic acid (6a), 4α-carboxygrindelic acid (7a), 17-hydroxygrindelic acid (8a), 6α-hydroxygrindelic acid (9a), 8,17-bisnor-8-oxagrindelic acid (10a), 7α,8α-epoxygrindelic acid (11a), and strictanonic acid (12a) as methyl esters were obtained from an Argentine collection of Grindelia chiloensis (Cornel.) Cabrera. Their structures and relative configurations were established on the basis of spectroscopic analysis. CHCl3 extract from the aerial parts and their pure compounds were evaluated for their antifungal and depigmenting effects. Methyl ester derivative of 10a (10b) exhibited a remarkable mycelial growth inhibition against Botritis cinerea with an IC50 of 13.5 µg ml-1 . While the new grindelane 1b exerted a clear color reduction of the yellow-orange pigment developed by Fusarium oxysporum against UV-induced damage.

Volatiles from Subtropical Convolvulaceae That Interfere with Bacterial Cell-to-Cell Communication as Potential Antipathogenic Drugs.

Increasing chronic bacterial infections create an urgent need for new antimicrobial agents or strategies for their control. Targeting virulence is one of the alternative approaches to find new medicines to treat persistent infections due to bacteria with biofilm-phenotype which are more resistant to antibiotics than their planktonic counterparts having an extreme capacity for evading the host defences. A bioguided study of sixteen extracts from flowers and leaves of four subtropical Convolvulaceae species provided evidence of the occurrence of antipathogenic natural products active against Gram positive and negative bacteria. Particularly, volatile metabolites from Merremia dissecta creeper, a food and medicinal plant, were able to interfere with the Pseudomonas aeruginosa quorum sensing system by a strong decrease of N-acyl homoserine lactone (AHL) biosynthesis (63-75%), which attenuated the virulence factor expression like biofilm (55%) and elastase activity (up to 27%), key factors that enable the colonization and dissemination of the infection in the host. Control of the P. aeruginosa biofilm and the QS process by phytochemicals, such as (+) spathulenol, isolated from a bioactive extract of M. dissecta leaves would be a good strategy for the development of new and effective antipathogenic drugs.

A Puna Collection of Senecio punae, Main Source of a Versatile Eremophilane-type Ketone.

Senecio punae Cabrera (Asteraceae-Senecioneae) is an endemic species from Puna semi-desert region of Argentina.The major compound, 4p,5p-eremophil- 7(11)9-dien-8-one, also known as dehydrofukinone (D), was isolated from the diethyl ether extract (E) of the plant. The phytochemical constituents from S. punae are presented here for the first time, as well as bioassays employing D, a molecule with versatility to carry out many different biological activities. E and D showed acute molluscicidal activity against the bilharzia vector snail Biomphalaria peregrina with LD50 values of 68.6 and 16.7 pg/mL, respectively. D exerted moderate and strong effects against promastigotes of Leishmania amazonensis and L. braziliensis, with IC5s values of 34.3?1.2 and 9.93+0.17 Ag/mL, respectively. Antibacterial effects were also found. Diethyl ether extract (E) and dehydrofukinone (D) were slightly active against Pseudomonas aeruginosa and Staphylococcus aureus at 50 and 25 tg/mL, respectively. However, D and E improved the effectiveness of oxacillin at 6 ig/mL against S. aureus growth and its biofilm, but did not affect beneficial lactobacilli strains. Synergistic effects were also measured between D (23 gg/mL) and ciprofloxacin (0.25 pg/mL) against two P. aeruginosa strains (FIC index = 0.38), as well as against two S. aureus strains (FIC indexes = 0.38 and 0.25). Finally, when 250 pg of either dehydrofukinone (D) or diethyl ether extract (E) were incorporated into the diet of the pest Oryzaephillus surinamensis, an alteration in the feeding behavior of the insect (Repellency indexes = +60 and +10, respectively) was observed.

Natural sesquiterpene lactones enhance oxacillin and gentamicin effectiveness against pathogenic bacteria without antibacterial effects on beneficial lactobacilli.

This is a report on the synergistic interactions (SIs) between melampolide-type sesquiterpene lactones 1-8 from Acanthospermum hispidum DC., and oxacillin or gentamicin, against four pathogenic strains of Staphylococcus aureus and Enterococcus faecalis; two of them were multi-resistant strains obtained from chronic infectious processes. Our results showed that all associations of 1-8 with antibiotics (ATBs) are more effective than pure ATBs to control pathogenic strains of S. aureus and E. faecalis. The most relevant SIs were observed when the major lactone of A. hispidum, acanthospermal B [5], was combined with gentamicin (protein synthesis inhibitor) against an ex vivo culture of methicillin-resistant S. aureus SAR 1, displaying a significant MIC reduction in 5 (312.5 to 78.1 µg/mL), and gentamicin (120 µg/mL to 3 µg/mL). Compound 4 improved the antibiotic potency of oxacillin (cell wall synthesis inhibitor) against ampicillin-resistant E. faecalis (60 µg/mL to 1.5 µg/mL). It is important to remark that three beneficial lactobacilli were resistant to 1-8 and their mixtures with gentamicin or oxacillin in effective concentrations against pathogenic bacteria. Synergism between ATBs and phytochemicals is a therapeutically helpful concept to improve ATB efficacy and prevent resistance. The present results show that selective SIs occur between melampolides and gentamicin or oxacillin, and open a new field of research.

Penicillium commune metabolic profile as a promising source of antipathogenic natural products.

Penicillium is an important genus of ascomycetous fungi in the environment and in food and drug production. This paper aims to investigate statins and antipathogenic natural products from a Penicillium commune environmental isolate. Fractions (F1, F2, F3 and F4) were obtained from an ethyl acetate extract. Direct insertion probe/electron ionisation/ion trap detection mass spectrometry (MS and MS/MS) identified lovastatin (1) in F1, while GC-MS showed that 3-isobutylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione (2) was the main constituent of F2 (49.34%). F4 presented 3 (16.38%) as an analogue of 2 and their known structures were similar to that of an autoinducer-signal. F1 produced a significant decrease in the Pseudomonas aeruginosa biofilms, which is the main cause of bacterial pathogenicity. F2 and F4 were effective against Staphylococcus aureus biofilms, but when F2 was associated with oxacillin, it showed an important activity against both bacteria. These novel results suggest that P. commune INTA1 is a new source of promising antipathogenic products.

Bioactivity of the essential oil of an argentine collection of Acanthospermum hispidum (Asteraceae).

The essential oil of an Argentine collection of the annual herb Acanthospermum hispidum DC. (Asteraceae), which contains the sesquiterpenoids beta-caryophyllene (35.2%), alpha-bisabolol (11.4%), and germacrene D (11.1%) as major constituents, displayed molluscicidal effects on an adult population of Biomphalaria peregrina Orbigny (LD50 37.8 microg/mL) and produced alteration of the feeding and oviposition behavior of the polyphagous insect Spodoptera frugiperda Smith when incorporated in the larval diet at 250 microg/g. In addition, a selective antibacterial activity was observed against pathogenic strains of Staphylococcus aureus and Enterococcus faecalis (MICs 62.5 and 125 microg/mL), but was inactive at 125 microg/mL against three beneficial lactic acid bacteria. Synergistic interactions were further validated by FIC index determination of the combination of the antibiotics oxacillin and gentamicin and the essential oil on the four pathogenic strains evaluated.

In vivo and in vitro antibacterial activity of acanthospermal B, a sesquiterpene lactone isolated from Acanthospermum hispidum.

Acanthospermal B (AcB), the major sesquiterpene lactone (SL) of Acanthospermum hispidum, an herb widely spread in Argentina, is a selective antibacterial agent against Enterococcus faecalis and Staphylococcus aureus, but inactive on Gram-negative and Lactobacillus. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main microorganisms involved in human chronic infection. A balb\c mouse skin infection model was developed to reproduce the lesions caused by acute and chronic infections produced by MRSA. After determination of the maximum concentration of AcB unable to produce tissular injury after intradermal injection, the anti-MRSA effect of AcB was evaluated on skin, liver and spleen tissues of infected mice. AcB, at doses of 2.5 mg/kg, produced a ten times decrease of MRSA growth in skin infection. In addition, the same dose prevented the dissemination to liver and/or spleen. AcB also displayed a bacteriostatic effect, in vitro, on MRSA cultures at 50 µg/mL that seems to be caused by partial denaturation of total bacterial DNA and/or inhibition of the PCR reaction in not denaturized DNA. Finally, total MRSA cell wall lysis occurred at a concentration of 100 µg/mL of AcB after 2 h of exposure.

Bioactive plants from Argentina and Bolivia.

Antibacterial and molluscicidal activities of methanol and chloroform extracts of 16 plant species belonging to the families Compositae and Melastomataceae were evaluated. The chloroform extract of Vernonanthura tweediana and the methanol extract of Senecio santelisis resulted to be very toxic to brine shrimp nauplii (LC(50)=1 microg/ml). Chloroform extracts of S. santelisis and Senecio leucostachys as well as the methanol extract of Wedelia subvaginata displayed molluscicidal effects on Biomphalaria peregrina showing LC(100)<100 microg/ml. Moderate antibacterial action was produced by the chloroform extracts of Flaveria bidentis, Grindelia scorzonerifolia and Vernonia incana against two strains of Staphylococcus aureus.

Effects of plant lactones on the production of biofilm of Pseudomonas aeruginosa.

Sixteen plant sesquiterpene lactones, thirteen from four species of the Family Asteraceae, and three from a species of Hepaticae, as well as seven annonaceous acetogenins isolated from the seeds of the tropical tree Annona cherimolia (Family Annonaceae), were evaluated for their ability to inhibit or stimulate the production of biofilm by a strain of Pseudomonas aeruginosa. The tested compounds carry a gamma-lactone moiety in their structures. This structural feature is similar to the lactone moiety present in N-acyl homoserine lactones, compounds that play the important role of "quorum sensors" in the mechanisms of biofilm formation observed in many gram-negative bacteria. A special assay was employed to evaluate the influence of the tested plant compounds to inhibit or stimulate the production of biofilm in a P. aeruginosa wild strain. Most of the tested compounds affected the biofilm formation mechanism. Six sesquiterpene lactones isolated from Acanthospermum hispidum and one from Enydra anagallis as well as an acetogenin from Annona cherimolia strongly inhibited (69-77%) the biofilm formation when incorporated to a bacterial culture at a concentration of 2.5 microg/ml. However, one of the acetogenins, squamocin, stimulated the biofilm formation even at a concentration of 0.25 microg/ml. The study of substances affecting the biofilm formation can lead to the design of new strategies to control P. aeruginosa infections.