83 research outputs found

    Control of Propionibacterium acnes by natural antimicrobial substances: Role of the bacteriocin AS-48 and lysozyme

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    We report the high susceptibility of several clinical isolates of Propionibacterium acnes from different sources (skin, bone, wound exudates, abscess or blood contamination) to the head-to-tail cyclized bacteriocin AS-48. This peptide is a feasible candidate for further pharmacological development against this bacterium, due to its physicochemical and biological characteristics, even when it is growing in a biofilm. Thus, the treatment of pre-formed biofilms with AS-48 resulted in a dose- and time-dependent disruption of the biofilm architecture beside the decrease of bacterial viability. Furthermore, we demonstrated the potential of lysozyme to bolster the inhibitory activity of AS-48 against P. acnes, rendering high reductions in the MIC values, even in matrix-growing cultures, according to the results obtained using a range of microscopy and bioassay techniques. The improvement of the activity of AS-48 through its co-formulation with lysozyme may be considered an alternative in the control of P. acnes, especially after proving the absence of cytotoxicity demonstrated by these natural compounds on relevant human skin cell lines. In summary, this study supports that compositions comprising the bacteriocin AS-48 plus lysozyme must be considered as promising candidates for topical applications with medical and pharmaceutical purposes against dermatological diseases such as acne vulgaris.This research was funded by a grant from the Spanish Ministry of Economy and Competitiveness (SAF2013-48971-C2-1-R that included funds from European Regional Development, ERDF), and the Research Group General (BIO160, UGR)

    Beyond outputs: pathways to symmetrical evaluations of university sustainable development partnerships

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    As the United Nations Decade of Education for Sustainable Development (2005–2014) draws to a close, it is timely to review ways in which the sustainable development initiatives of higher education institutions have been, and can be, evaluated. In their efforts to document and assess collaborative sustainable development program outcomes and impacts, universities in the North and South are challenged by similar conundrums that confront development agencies. This article explores pathways to symmetrical evaluations of transnationally partnered research, curricula, and public-outreach initiatives specifically devoted to sustainable development. Drawing on extensive literature and informed by international development experience, the authors present a novel framework for evaluating transnational higher education partnerships devoted to sustainable development that addresses design, management, capacity building, and institutional outreach. The framework is applied by assessing several full-term African higher education evaluation case studies with a view toward identifying key limitations and suggesting useful future symmetrical evaluation pathways. University participants in transnational sustainable development initiatives, and their supporting donors, would be well-served by utilizing an inclusive evaluation framework that is infused with principles of symmetry

    Selectively targeting bacteria by tuning the molecular design of membrane-active peptidomimetic amphiphiles

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    Here we report the design of membrane-active peptidomimetic molecules with a tunable arrangement of hydrophobic and polar groups. In spite of having the same chemical composition, the effective hydrophobicities of the compounds were different as a consequence of their chemical structure and conformational properties. The compound with lower effective hydrophobicity demonstrated antibacterial activity that was highly selective towards bacteria over mammalian cells. This study, highlighting the role in membrane selectivity of the specific arrangement of the different moieties in the molecular structure, provides useful indications for developing non-toxic antibacterial agents

    Lysine-Based Small Molecules That Disrupt Biofilms and Kill both Actively Growing Planktonic and Nondividing Stationary Phase Bacteria

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    The emergence of bacterial resistance is a major threat to global health. Alongside this issue, formation of bacterial biofilms is another cause of concern because most antibiotics are ineffective against these recalcitrant microbial communities. Ideal future antibacterial therapeutics should possess both antibacterial and anti-biofilm activities. In this study we engineered lysine-based small molecules, which showed not only commendable broad-spectrum antibacterial activity but also potent biofilm-disrupting properties. Synthesis of these lipophilic lysine–norspermidine conjugates was achieved in three simple reaction steps, and the resultant molecules displayed potent antibacterial activity against various Gram-positive (Staphylococcus aureus, Enterococcus faecium) and Gram-negative bacteria (Escherichia coli) including drug-resistant superbugs MRSA (methicillin-resistant <i>S. aureus</i>), VRE (vancomycin-resistant <i>E. faecium</i>), and β-lactam-resistant Klebsiella pneumoniae. An optimized compound in the series showed activity against planktonic bacteria in the concentration range of 3–10 μg/mL, and bactericidal activity against stationary phase <i>S. aureus</i> was observed within an hour. The compound also displayed about 120-fold selectivity toward both classes of bacteria (<i>S. aureus</i> and <i>E. coli</i>) over human erythrocytes. This rapidly bactericidal compound primarily acts on bacteria by causing significant membrane depolarization and K<sup>+</sup> leakage. Most importantly, the compound disrupted preformed biofilms of <i>S. aureus</i> and did not trigger bacterial resistance. Therefore, this class of compounds has high potential to be developed as future antibacterial drugs for treating infections caused by planktonic bacteria as well as bacterial biofilms

    Fatty Acid Comprising Lysine Conjugates: Anti-MRSA Agents That Display In Vivo Efficacy by Disrupting Biofilms with No Resistance Development

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    Methicillin-resistant Staphylococcus aureus (MRSA) has developed resistance to antibiotics of last resort such as vancomycin, linezolid, and daptomycin. Additionally, their biofilm forming capability has set an alarming situation in the treatment of bacterial infections. Herein we report the potency of fatty acid comprising lysine conjugates as novel anti-MRSA agents, which were not only capable of killing growing planktonic MRSA at low concentration (MIC = 3.1–6.3 μg/mL), but also displayed potent activity against nondividing stationary phase cells. Furthermore, the conjugates eradicated established biofilms of MRSA. The bactericidal activity of d-lysine conjugated tetradecanoyl analogue (D-LANA-14) is attributed to its membrane disruption against these metabolically distinct cells. In a mouse model of superficial skin infection, D-LANA-14 displayed potent in vivo anti-MRSA activity (2.7 and 3.9 Log reduction at 20 mg/kg and 40 mg/kg, respectively) without showing any skin toxicity even at 200 mg/kg of the compound exposure. Additionally, MRSA could not develop resistance against D-LANA-14 even after 18 subsequent passages, whereas the topical anti-MRSA antibiotic fusidic acid succumbed to rapid resistance development. Collectively, the results suggested that this new class of membrane targeting conjugates bear immense potential to treat MRSA infections over conventional antibiotic therapy

    Mechanical properties of Aningeria superba (Aningre) and Austranella congolensis tannin adhesives

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    The Spiroplasma Motility Inhibition Test, a New Method for Determining Intraspecific Variation among Colorado Potato Beetle Spiroplasmas

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    The Colorado potato beetle, Leptinotarsa decemlineata, is a major holarctic pest of solanaceous crops. Presumably, this insect spread from Solanum species in central America to the Mexican plateau, and this was followed by multiple invasions of North America and Europe. Attempts are being made to control this beetle by using a genetically modified spiroplasma that occurs naturally in its gut. In the current study, spiroplasmas isolated from beetles collected in North America and Poland exhibited serologic (spiroplasma motility inhibition test) and genomic (restriction fragment length polymorphism) profiles that suggest that there were multiple spiroplasma introductions. Two serovars were identified; one is found in northern North America and at high elevations in Poland, and the other is found in southern North America and at low elevations in Poland. The patterns of genovar distribution coincide with the serovar patterns. The existence of such biovars—intraspecific taxal units reflected by serologic and genomic differences—should be taken into consideration when taxonomies are developed and strains are chosen for biocontrol
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