Elena Cartagena

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. Copyright

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.

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.

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. Copyright

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.

A New Depigmenting-Antifungal Methylated Grindelane from Grindelia chiloensis.

The new methylated grindelane diterpenoid, 7β‐hydroxy‐8(17)‐dehydrogrindelic acid (1b), together with the known 7α‐hydroxy‐8(17)‐dehydrogrindelic acid (2a), 6‐oxogrindelic acid (3a), 4β‐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.