Project description:The increasing onset of multidrug-resistant bacteria has propelled microbiology research towards antimicrobial peptides as new possible antibiotics from natural sources. Antimicrobial peptides are short peptides endowed with a broad range of activity against both Gram-positive and Gram-negative bacteria and are less prone to trigger resistance. Besides their activity against planktonic bacteria, many antimicrobial peptides also show antibiofilm activity. Biofilms are ubiquitous in nature, having the ability to adhere to virtually any surface, either biotic or abiotic, including medical devices, causing chronic infections that are difficult to eradicate. The biofilm matrix protects bacteria from hostile environments, thus contributing to the bacterial resistance to antimicrobial agents. Biofilms are very difficult to treat, with options restricted to the use of large doses of antibiotics or the removal of the infected device. Antimicrobial peptides could represent good candidates to develop new antibiofilm drugs as they can act at different stages of biofilm formation, on disparate molecular targets and with various mechanisms of action. These include inhibition of biofilm formation and adhesion, downregulation of quorum sensing factors, and disruption of the pre-formed biofilm. This review focuses on the proprieties of antimicrobial and antibiofilm peptides, with a particular emphasis on their mechanism of action, reporting several examples of peptides that over time have been shown to have activity against biofilm.
Project description:THE TITLE SESQUITERPENE [SYSTEMATIC NAME: 6-methoxy-10-methyl-7-(propan-2-yl)-2-oxatricyclo[6.3.1.0(4,12)]dodeca-1(11),4,6,8(12),9-pentaen-5-ol], C(16)H(18)O(3), was isolated from pathogen-infected stele tissue of Gossypium barbadense. There are two mol-ecules in the asymmetric unit and the dihedral angle between their naphtho-furan systems is 86.48 (2)°. In the crystal, O-H⋯O hydrogen bonds between the hy-droxy groups and etheric O atoms link the mol-ecules into centrosymmetric tetra-mers. These tetra-mers are assembled into (010) layers via stacking inter-actions between the naphtho-furan systems [inter-planar distance 3.473 (3) Å] and short C-H⋯O contacts.
Project description:The title compound, C16H20O3 [systematic name: 1-hy-droxy-7-meth-oxy-1,6-dimethyl-4-(propan-2-yl)naphthalen-2(1H)-one], is a sesquiterpene isolated from foliar tissues of the cotton plant and is of inter-est with respect to its anti-bacterial properties. Its phenyl ring is ideally planar, and the maximum of deviation in the second ring is 0.386 (3) Å. The hy-droxy group and the methyl group are oriented in an equatorial fashion and axial, respectively, to the second ring. In the crystal, inversion dimers are formed through pairs of O-H⋯O hydrogen bonds. Weak C-H⋯O hydrogen bonds link the dimers into columns along the c axis. These columns form a crystal structure with a crystal packing factor of 0.66.
Project description:The title mol-ecule, (E)-2,3',4,5-tetra-methoxy-stilbene, C(18)H(20)O(4), is virtually planar. The angle between the two benzene rings is 4.06?(6)°. The inter-molecular inter-actions present in the structure are weak. There are C-H?O hydrogen bonds and C-H??-electron ring inter-actions. The mol-ecules are ordered into planes that are parallel to (01). The distance between adjacent planes is about 3.3?Å and therefore ?-? electron inter-actions between the aromatic planes are also plausible.
Project description:The title compound (AME; systematic name: 3,7-dihy-droxy-9-meth-oxy-1-methyl-6H-benzo[c]chromen-6-one), C(15)H(12)O(5), was isolated from an endophytic fungi Alternaria sp., from Catharanthus roseus (common name: Madagascar periwinkle). There is an intramolecular O-H⋯O hydrogen bond in the essentially planar mol-ecule (r.m.s. deviation 0.02 Å). In the crystal, the molecule forms an O-H⋯O hydrogen bond with its centrosymmetric counterpart with four bridging inter-actions (two O-H⋯O and two C-H⋯O). The almost planar sheets of the dimeric units thus formed are stacked along b axis via C-H⋯π and π-π contacts [with C⋯C short contacts between aromatic moieties of 3.324 (3), 3.296 (3) and 3.374 (3) Å].
Project description:The title compound [MOM-SalB; systematic name: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(3-fur-yl)-9-meth-oxy-meth-oxy-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octa-hydro-1H-benzo[f]isochromene-7-carboxyl-ate], C(23)H(30)O(8), is a deriv-ative of the ?-opioid salvinorin A with enhanced potency, selectivity, and duration of action. Superimposition of their crystal structures reveals, surprisingly, that the terminal C and O atoms of the MOM group overlap with the corresponding atoms in salvinorin A, which are separated by an additional bond. This counter-intuitive isosterism is possible because the MOM ether adopts the 'classic anomeric' conformation (gauche-gauche), tracing a helix around the planar acetate of salvinorin A. This overlap is not seen in the recently reported structure of the tetra-hydro-pyranyl ether, which is less potent. The classic anomeric conformation is strongly favoured in alk-oxy-methyl ethers, but not in substituted acetals, which may contribute to their reduced potency. This structure may prove useful in evaluating models of the activated ?-opioid receptor.
Project description:The title compound isolated from Areca catechu L. (common name: arborinol methyl ether; a member of the arborane family) was established as 3α-methoxyarbor-9(11)-ene, C(31)H(52)O. Rings A/B/C/D assume a chair conformation, while ring E has an envelope conformation. The absolute configuration was determined to be (3R,5R,8S,10S,13R,14S,17S,18S, 21S) by analysis of Bijvoet pairs based on resonant scattering of light atoms, yielding a Hooft parameter y of -0.03 (3).
Project description:Organisms that accumulate calcium carbonate structures are particularly vulnerable to ocean warming (OW) and ocean acidification (OA), potentially reducing the socioeconomic benefits of ecosystems reliant on these taxa. Since rising atmospheric CO2 is responsible for global warming and increasing ocean acidity, to correctly predict how OW and OA will affect marine organisms, their possible interactive effects must be assessed. Here we investigate, in the field, the combined temperature (range: 16-26 °C) and acidification (range: pHTS 8.1-7.4) effects on mortality and growth of Mediterranean coral species transplanted, in different seasonal periods, along a natural pH gradient generated by a CO2 vent. We show a synergistic adverse effect on mortality rates (up to 60%), for solitary and colonial, symbiotic and asymbiotic corals, suggesting that high seawater temperatures may have increased their metabolic rates which, in conjunction with decreasing pH, could have led to rapid deterioration of cellular processes and performance. The net calcification rate of the symbiotic species was not affected by decreasing pH, regardless of temperature, while in the two asymbiotic species it was negatively affected by increasing acidification and temperature, suggesting that symbiotic corals may be more tolerant to increasing warming and acidifying conditions compared to asymbiotic ones.
Project description:Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents. Here, we tested the ability of an eCAP, WLBU2, to disrupt recalcitrant Pseudomonas aeruginosa biofilms. WLBU2 was capable of significantly reducing biomass and viability of P. aeruginosa biofilms formed on airway epithelium and maintained activity during viral coinfection, a condition that confers extraordinary levels of antibiotic resistance. Biofilm disruption was achieved in short treatment times by permeabilization of bacterial membranes. Additionally, we observed simultaneous reduction of infectivity of the viral pathogen respiratory syncytial virus (RSV). WLBU2 is notable for its ability to maintain activity across a broad range of physiological conditions and showed negligible toxicity toward the airway epithelium, expanding its potential applications as an antimicrobial therapeutic. IMPORTANCE Antimicrobial-resistant infections are an urgent public health threat, making development of novel antimicrobials able to effectively treat these infections extremely important. Chronic and polymicrobial infections further complicate antimicrobial therapy, often through the development of microbial biofilms. Here, we describe the ability of an engineered antimicrobial peptide to disrupt biofilms formed by the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogen Pseudomonas aeruginosa during coinfection with respiratory syncytial virus. We also observed antiviral activity, indicating the ability of engineered antimicrobial peptides to act as cross-kingdom single-molecule combination therapies.
Project description:Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications.