Realistic and critical review of the state of systemic anti-microbial peptides

Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility of adding new candidates to the list of the existing peptide antibiotics to more effectively combat antibiotic-resistant bacteria, fungi, and parasites

Expanding the Landscape of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment in Nature, Implications for Peptide Design and Therapeutic Potential

Unlike the α-helical and β-sheet antimicrobial peptides (AMPs), our knowledge on amino acid-rich AMPs is limited. This article conducts a systematic study of rich AMPs (\u3e25%) from different life kingdoms based on the Antimicrobial Peptide Database (APD) using the program R. Of 3425 peptides, 724 rich AMPs were identified. Rich AMPs are more common in animals and bacteria than in plants. In different animal classes, a unique set of rich AMPs is deployed. While histidine, proline, and arginine-rich AMPs are abundant in mammals, alanine, glycine, and leucine-rich AMPs are common in amphibians. Ten amino acids (Ala, Cys, Gly, His, Ile, Lys, Leu, Pro, Arg, and Val) are frequently observed in rich AMPs, seven (Asp, Glu, Phe, Ser, Thr, Trp, and Tyr) are occasionally observed, and three (Met, Asn, and Gln) were not yet found. Leucine is much more frequent in forming rich AMPs than either valine or isoleucine. To date, no natural AMPs are simultaneously rich in leucine and lysine, while proline, tryptophan, and cysteine-rich peptides can simultaneously be rich in arginine. These findings can be utilized to guide peptide design. Since multiple candidates are potent against antibiotic-resistant bacteria, rich AMPs stand out as promising future antibiotics

Realistic and Critical Review of the State of Systemic Anti-Microbial Peptides

Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility of adding new candidates to the list of the existing peptide antibiotics to more effectively combat antibiotic-resistant bacteria, fungi, and parasites

Systematic review of Ethiopian medicinal plants used for their anti-inflammatory and wound healing activities

Ethnopharmacological relevance: Plant materials are used worldwide as complementary and alternative therapeutics for the treatment of various illnesses. In Ethiopia, folk medicines are utilized across a wide range of cultures and settings. Ethiopia has numerous plant species of which around 12% are endemic, making it a rich source of medicinal plants that are potentially important for human wellbeing. Aim of the study: The aim of this study was to assess Ethiopian medicinal plants with anti-inflammatory or wound healing activities, in an attempt to compile the information required for further investigation of their potential role in the management of lymphoedema. Methods: A systematic review protocol was developed according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The protocol for this review was registered on PROSPERO with registration number CRD42019127471. This review considers all controlled in vivo and in vitro anti-inflammatory and wound healing studies evaluating the efficacy and safety of Ethiopian medicinal plants. The search strategy included all articles containing descriptors such as Ethiopia, medicinal plants, herbal products, care, management, lymphoedema, lymphedema, swelling, podoconiosis, elephantiasis, wound, wound healing, inflammation, and anti-inflammatory that were published up to June 28, 2019. Outcomes were measured as the percentage of inflammatory and pro-inflammatory cell inhibition, as the percentage of carrageenan-induced oedema (anti-inflammation) inhibition, and the percentage of cell migration and proliferation (wound healing). For quality assessment of individual animal studies, the Risk of Bias tool for animal intervention studies (SYRCLE’s RoB tool) criteria was used. For quality assessment of individual in vitro studies, the OECD guidelines and the WHO Good Laboratory Practice (GLP) handbook were used. Results: A total of 46 articles on anti-inflammatory and 17 articles on wound healing properties were reviewed. For the in vivo studies, Swiss albino mice and Wistar rats were used, and the concentration of plant extracts or fractions administered to the lab animals varied considerably. Acetone extract of Vernonia amygdalina showed the fastest anti-inflammatory activity at lower concentrations in carrageenan-induced paw oedema. Conclusion: Lawsonia inermis, Azadirachta indica, Achyranthes aspera, and Cuminum cyminum are the most studied plant species in terms of anti-inflammatory activity, while Lawsonia inermis and Azadirachta indica are the most studied for wound healing. The most common in vivo techniques used for the anti-inflammatory and the wound healing assays were carrageenan-induced paw oedema, and excision and incision wound models, respectively

Methyl gallate and tylosin synergistically reduce the membrane integrity and intracellular survival of Salmonella Typhimurium.

Nymphaea tetragona Georgi (Nymphaceae) is traditionally used in Asia for the treatment of diarrhea, dysentery and fever. The plant contains various active compounds, including methyl gallate (MG) which are reported to inhibit bacterial virulence mechanisms. This study aimed to evaluate the alterations on viability, membrane potential and integrity of Salmonella enterica Serovar Typhimurium exposed to MG in combination with Tylosin (Ty), which is relatively inactive against Gram-negative bacteria, but it is commonly used as a feed additive in livestock. Besides, the effects of sub-inhibitory concentrations of the combination (MT) on the interaction between S. Typhimurium and the host cell, as well as on the indirect host responses, were characterized. Flow cytometry, confocal and electron microscopic examinations were undertaken to determine the effects of MT on S. Typhimurium. The impacts of sub-inhibitory concentrations of MT on biofilm formation, as well as on the adhesion, invasion and intracellular survival of S. Typhimurium were assessed. The result demonstrated significant damage to the bacterial membrane, leakage of cell contents and a reduction in the membrane potential when treated with MT. Sub-inhibitory concentrations of MT significantly reduced (P < 0.05) the biofilm-forming, adhesive and invasive abilities of S. Typhimurium. Exposure to MT drastically reduced the bacterial count in macrophages. Up-regulation of interleukin (IL)-6, IL-8 and IL-10 cytokine genes were detected in intestinal epithelial cells pre-treated with MT. This report is the first to describe the effects of MT against S. Typhimurium. The result indicates a synergistic interaction between MG and Ty against S. Typhimurium. Therefore, the combination may be a promising option to combat S. Typhimurium in swine and, indirectly, safeguard the health of the public

Additional file 3: of Knowledge, attitudes and practices towards rabies: questionnaire survey in rural household heads of Gondar Zuria District, Ethiopia

Table S3. Time to look for treatment and treatment preferences

Spraying of swine buildings with lemon grass (Cymbopogon citratus) essential oil does not produce blood absorption in swine

Cymbopogon citratus (Lemon grass) essential oils have been used in swine buildings to reduce the offensive odor emanating from swine buildings. The present study was designed to investigate plasma residues of citral which is a major constituent of the essential oils of Cymbopogon citratus. An HPLC method was established, validated and used for the determination of citral in swine plasma harvested from blood samples taken at the 14th, 21st and 28th day after spraying swine buildings with the 3% Lemon grass essential oil. Thereafter, analysis of the sample was conducted using HP ODS Hypersil column (200 × 4.6 mm, 5 µm) with a mobile phase consisting of methanol and 0.5% acetic acid; and a flow rate of 1mL/ min. The method was validated for parameters such as accuracy, precision, linearity and detection limits. Plasma spiked with standard citral (95%) revealed two chromatograms with retention times of about 10.7 and 12.2 minutes. The calibration curves for the citral isomers were found to be linear in the tested concentration ranges and mean recoveries wre 101% and 99.17%. This method was used to determine the residues of citral in swine plasma pretreated with methanol. Surprisingly, there was no any detectable level of citral in swine plasma within the 28 days of exposure.spraying of swine buildings with essential oils of lemon grass oil does not cause plasma residues of citral.

Preventive effects of a novel herbal mixture on atopic dermatitis-like skin lesions in BALB/C mice

Abstract Background A combination of parts of Cornus officinalis, Rosa multiflora, Lespedeza bicolor, Platycladus orientalis, and Castanea crenata is commonly used for alleviating inflammatory skin disorders. Therefore, this study was carried out to evaluate the in vitro and in vivo preventive effects of a novel herbal formula made from the five plants (C2RLP) against atopic dermatitis in BALB/C mice. Methods Mice were allocated into five groups (n = 8) including, control (Normal, petrolatum, and betamethasone treated) and treatment groups (treated with 2.5 and 5% C2RLP ointment). Atopic lesion was induced by applying 1-Chloro-2, 4-dinitrobenzene to the dorsal thoracic area of mice. Macroscopical and histological evaluations were performed to determine the effects of treatment on the progress of the skin lesions. The effects of treatment on the production and release of interleukins, interferon -ϒ, nitrite, prostaglandin E2, thymus and activation-receptor chemokine, and β-hexosaminidase were evaluated and comparisons were made between groups. In addition, the chemical compounds present in C2RLP were identified by Liquid Chromatography-Mass Spectrometry. Results Topical application of C2RLP reduced the dermatitis score and suppressed histopathological changes in mice. Treatment significantly reduced (P < 0.05) plasma IL-4 level, the production of nitrite, prostaglandin E2, and thymus and activation-receptor chemokine production. The lipopolysaccharide-induced iNOS-mRNA expression in RAW 264.7 cells was also suppressed by high concentrations of C2RLP. In addition, C2RLP showed an inhibitory effect against DPPH free radical (IC50 = 147.5 μg/ml) and β-hexosaminidase release (IC50 = 179.5 μg/ml). Liquid Chromatography-Mass Spectrometry analysis revealed the presence of various compounds, including loganin, ellagic acid, and kaempferol 3-glucoside. Conclusion Down-regulation of T- helper 2 cellular responses and suppression of inflammatory mediators contributed to the protective effects of C2RLP from atopic dermatitis in BALB/C mice

Imipenem Resistance Mediated by blaOXA-913 Gene in Pseudomonas aeruginosa

Treatment of infectious diseases caused by carbapenem-resistant Pseudomonas aeruginosa is becoming a greater challenge. This study aimed to identify the imipenem resistance mechanism in P. aeruginosa isolated from a dog. Minimum Inhibitory Concentration (MIC) was determined by the broth microdilution method according to the Clinical and Laboratory Standards Institute recommendations. We performed polymerase chain reaction and whole-genome sequencing to detect carbapenem resistance genes. Genomic DNA of P. aeruginosa K19PSE24 was sequenced via the combined analysis of 20-kb PacBio SMRTbell and PacBio RS II. Peptide-Peptide Nucleic Acid conjugates (P-PNAs) targeting the translation initiation region of blaOXA-913 were synthesized. The isolate (K19PSE24) was resistant to imipenem and piperacillin/tazobactam yet was susceptible to most of the tested antimicrobials. Whole-genome sequencing revealed that the K19PSE24 genome comprised a single contig amounting to 6,815,777 base pairs, with 65 tRNA and 12 rRNA genes. K19PSE24 belonged to sequence type 313 and carried the genes aph(3)-IIb, fosA, catB7, crpP, and blaOXA-913 (an allele deposited in GenBank but not described in the literature). K19PSE24 also carried genes encoding for virulence factors (exoenzyme T, exotoxin A, and elastase B) that are associated with adhesion, invasion, and tissue lysis. Nevertheless, we did not detect any of the previously reported carbapenem resistance genes. This is the first report of the blaOXA-913 gene in imipenem-resistant P. aeruginosa in the literature. Notably, no viable colonies were found after co-treatment with imipenem (2 µg/mL) and either of the P-PNAs (12.5 µM or 25 µM). The imipenem resistance in K19PSE24 was primarily due to blaOXA-913 gene carriage

Mobile Colistin Resistance Gene mcr-1 Detected on an IncI2 Plasmid in Salmonella Typhimurium Sequence Type 19 from a Healthy Pig in South Korea

Colistin is considered the last resort for the treatment of multi-drug resistant Gram-negative bacterial infections. We studied colistin resistance and the mcr-1 gene carriage in Salmonella isolates recovered from food animals in South Korea between 2010 and 2018. Colistin resistance was found in 277 isolates, predominantly in Salmonella Enteritidis (57.1%) and Salmonella Gallinarum (41.9%). However, the mcr-1 gene was identified in only one colistin-resistant Salmonella Typhimurium (MIC = 16 µg/mL) isolated from a healthy pig. The mcr-1 carrying isolate presented additional resistance to multiple antimicrobials. The strain belonged to sequence type (ST)19 and carried various virulence factor genes that are associated with adhesion and invasion of Salmonella into intestinal epithelial cells, as well as its survival in macrophages. The mcr-1 gene was identified on an IncI2 plasmid and it was also transferred to the E. coli J53 recipient strain. The mcr-1-carrying plasmid (pK18JST013) in this study was closely related to that previously reported in S. Indiana (pCFSA664-3) from chicken in China. This is the first report of mcr-1 carrying S. Typhimurium in South Korea. The finding indicates the importance of regular screening for the presence of the mcr-1 gene in S. Typhimurium in food animals to prevent the spread to humans