Enhanced Membrane Pore Formation through High-Affinity Targeted Antimicrobial Peptides

Many cationic antimicrobial peptides (AMPs) target the unique lipid composition of the prokaryotic cell membrane. However, the micromolar activities common for these peptides are considered weak in comparison to nisin, which follows a targeted, pore-forming mode of action. Here we show that AMPs can be modified with a high-affinity targeting module, which enables membrane permeabilization at low concentration. Magainin 2 and a truncated peptide analog were conjugated to vancomycin using click chemistry, and could be directed towards specific membrane embedded receptors both in model membrane systems and whole cells. Compared with untargeted vesicles, a gain in permeabilization efficacy of two orders of magnitude was reached with large unilamellar vesicles that included lipid II, the target of vancomycin. The truncated vancomycin-peptide conjugate showed an increased activity against vancomycin resistant Enterococci, whereas the full-length conjugate was more active against a targeted eukaryotic cell model: lipid II containing erythrocytes. This study highlights that AMPs can be made more selective and more potent against biological membranes that contain structures that can be targeted

Antimicrobial Nodule-Specific Cysteine-Rich Peptides Induce Membrane Depolarization-Associated Changes in the Transcriptome of Sinorhizobium meliloti.

Leguminous plants establish symbiosis with nitrogen-fixing alpha- and betaproteobacteria, collectively called rhizobia, which provide combined nitrogen to support plant growth. Members of the inverted repeat-lacking clade of legumes impose terminal differentiation on their endosymbiotic bacterium partners with the help of the nodule-specific cysteine-rich (NCR) peptide family composed of close to 600 members. Among the few tested NCR peptides, cationic ones had antirhizobial activity measured by reduction or elimination of the CFU and uptake of the membrane-impermeable dye propidium iodide. Here, the antimicrobial spectrum of two of these peptides, NCR247 and NCR335, was investigated, and their effect on the transcriptome of the natural target Sinorhizobium meliloti was characterized. Both peptides were able to kill quickly a wide range of Gram-negative and Gram-positive bacteria; however, their spectra were only partially overlapping, and differences were found also in their efficacy on given strains, indicating that the actions of NCR247 and NCR335 might be similar though not identical. Treatment of S. meliloti cultures with either peptide resulted in a quick downregulation of genes involved in basic cellular functions, such as transcription-translation and energy production, as well as upregulation of genes involved in stress and oxidative stress responses and membrane transport. Similar changes provoked mainly in Gram-positive bacteria by antimicrobial agents were coupled with the destruction of membrane potential, indicating that it might also be a common step in the bactericidal actions of NCR247 and NCR335

Resistance of Gram-positive bacteria to nisin is not determined by Lipid II levels

Lipid II is essential for nisin-mediated pore formation at nano-molar concentrations. We tested whether nisin resistance could result from different Lipid II levels, by comparing the maximal Lipid II pool in Micrococcus flavus (sensitive) and Listeria monocytogenes (relatively insensitive) and their nisin-resistant variants, with a newly developed method. No correlation was observed between the maximal Lipid II pool and nisin sensitivity, as was further corroborated by using spheroplasts of nisin-resistant and wild-type strains of M. flavus, which were equally sensitive to nisin. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved

Національні тенденції розвитку університетської освіти

В сучасному динамічно змінюваному світі університет - це перш за все вищий навчальний заклад, який є індикатором цивілізаційності регіону та держави. Проте у наші дні класичні університети постали перед серйозними викликами часу.В современном динамически изменяющемся мире университет - это прежде всего высшее учебное заведение, которое является индикатором цивилизационности региона и государства. Однако в наши дни классические университеты встали перед серьезными вызовами времени

Transposition of the tendon of the M. tibialis posterior as an effective operative treatment of a drop foot

Objective. To evaluate the results of transposition of the tendon of the M. tibialis posterior in patients with a drop foot. Design. Descriptive, retrospective and follow-up investigation. Methods. Surgical treatment was carried out in 12 patients with a drop foot (9 women and 3 men, with an average age of 37 years) in the period 1986-1998. The aetiology of the drop foot was a traumatic or iatrogenic lesion of the peroneal nerve or sciatic nerve in 9 patients and in 3 patients spina bifida occulta, leprosy and a herniation of a lumbar disc respectively. None of the patients had important comorbidity. Treatment consisted of lengthening the Achilles tendon according to Huckstep, transposition of the tibial posterior tendon in two tails to the dorsomedial and dorsolateral side of the foot, and six weeks of immobilisation in plaster of Paris. Results. The postoperative period was without complications. The treatment improved the heel-toe steppage gait in all patients. None of the 10 patients who had used an orthosis preoperatively still used it at the time of the follow up. Fifty per cent of the patients acquired a dorsiflexion of the foot of more than 0°. The results were in accordance with those in the literature. Conclusion. Transposition of the tibial posterior tendon is a worthwhile alternative for those patients with a drop foot (and without important comorbidity) who cannot walk satisfactorily with an ankle-foot orthosis.</p

Transposition of the tendon of the M. tibialis posterior as an effective operative treatment of a drop foot

Objective. To evaluate the results of transposition of the tendon of the M. tibialis posterior in patients with a drop foot. Design. Descriptive, retrospective and follow-up investigation. Methods. Surgical treatment was carried out in 12 patients with a drop foot (9 women and 3 men, with an average age of 37 years) in the period 1986-1998. The aetiology of the drop foot was a traumatic or iatrogenic lesion of the peroneal nerve or sciatic nerve in 9 patients and in 3 patients spina bifida occulta, leprosy and a herniation of a lumbar disc respectively. None of the patients had important comorbidity. Treatment consisted of lengthening the Achilles tendon according to Huckstep, transposition of the tibial posterior tendon in two tails to the dorsomedial and dorsolateral side of the foot, and six weeks of immobilisation in plaster of Paris. Results. The postoperative period was without complications. The treatment improved the heel-toe steppage gait in all patients. None of the 10 patients who had used an orthosis preoperatively still used it at the time of the follow up. Fifty per cent of the patients acquired a dorsiflexion of the foot of more than 0°. The results were in accordance with those in the literature. Conclusion. Transposition of the tibial posterior tendon is a worthwhile alternative for those patients with a drop foot (and without important comorbidity) who cannot walk satisfactorily with an ankle-foot orthosis.</p

Transposition of the tendon of the M. tibialis posterior as an effective operative treatment of a drop foot

Objective. To evaluate the results of transposition of the tendon of the M. tibialis posterior in patients with a drop foot. Design. Descriptive, retrospective and follow-up investigation. Methods. Surgical treatment was carried out in 12 patients with a drop foot (9 women and 3 men, with an average age of 37 years) in the period 1986-1998. The aetiology of the drop foot was a traumatic or iatrogenic lesion of the peroneal nerve or sciatic nerve in 9 patients and in 3 patients spina bifida occulta, leprosy and a herniation of a lumbar disc respectively. None of the patients had important comorbidity. Treatment consisted of lengthening the Achilles tendon according to Huckstep, transposition of the tibial posterior tendon in two tails to the dorsomedial and dorsolateral side of the foot, and six weeks of immobilisation in plaster of Paris. Results. The postoperative period was without complications. The treatment improved the heel-toe steppage gait in all patients. None of the 10 patients who had used an orthosis preoperatively still used it at the time of the follow up. Fifty per cent of the patients acquired a dorsiflexion of the foot of more than 0°. The results were in accordance with those in the literature. Conclusion. Transposition of the tibial posterior tendon is a worthwhile alternative for those patients with a drop foot (and without important comorbidity) who cannot walk satisfactorily with an ankle-foot orthosis.</p