scholarly journals The Metabolic Stability of Antimicrobial Peptides IK8 in Plasma and Liver S9

2021 ◽  
Vol 11 (24) ◽  
pp. 11661
Author(s):  
Yingying Mao ◽  
Shaojun Zhou ◽  
Mingcheng Xu ◽  
Su Zeng ◽  
Weimin Fan ◽  
...  

In the face of mounting global antibiotic resistance, which has become a critical clinical problem, antimicrobial peptides (AMPs) have received considerable interest as new therapeutics with the efficacy for the treatment of multidrug-resistant (MDR) infections due to their novel mechanism. However, certain inherent shortcomings such as instability seriously limit their systemic applications in the clinic. In this study, we intend to clarify the connection between three configurations of IK8 and their stability in plasma and liver S9 of various species by confirming the metabolites. The structural information of these metabolites was scanned and identified using HPLC and Q-TOF, respectively. The results found that IK8-D exhibits superior stability, compared with IK8-2D and IK8-L in plasma and liver S9 incubation, which indicated D- type amino acids could significantly increase the stability of antimicrobial peptides.

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 522
Author(s):  
András Fodor ◽  
Birhan Addisie Abate ◽  
Péter Deák ◽  
László Fodor ◽  
Ervin Gyenge ◽  
...  

Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic resistance often reduces fitness, but compensatory mutations may counteract this tendency. The appearance of new antibiotic resistance is frequently accompanied by a collateral sensitivity to other resistances. Organisms with an expanding open pan-genome, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, can withstand an increased number of resistances by exploiting their evolutionary plasticity and disseminating clonally or poly-clonally. Multidrug-resistant pathogen clones can become predominant under antibiotic stress conditions but, under the influence of negative frequency-dependent selection, are prevented from rising to dominance in a population in a commensal niche. Antimicrobial peptides have a great potential to combat multidrug resistance, since antibiotic-resistant bacteria have shown a high frequency of collateral sensitivity to antimicrobial peptides. In addition, the mobility patterns of antibiotic resistance, and antimicrobial peptide resistance, genes are completely different. The integron trade in commensal niches is fortunately limited by the species-specificity of resistance genes. Hence, we theorize that the suggested post-antibiotic era has not yet come, and indeed might never come.


2021 ◽  
Vol 8 (1) ◽  
pp. e000695
Author(s):  
Amy L Johnson ◽  
Isanka U Ratnasekera ◽  
Katharine M Irvine ◽  
Andrew Henderson ◽  
Elizabeth E Powell ◽  
...  

ObjectiveMultiple factors predispose patients with cirrhosis to sepsis and/or bacteraemia and this has a high mortality rate. Within different geographical regions there are marked differences in the prevalence of infection with multidrug-resistant organisms (MDR). This study examined risk factors for and outcomes of sepsis/bacteraemia in public hospital admissions with cirrhosis in the state of Queensland, Australia, over the last decade, along with the bacterial pathogens responsible and their antibiotic susceptibility profiles.DesignA population-based retrospective cohort study of public hospital admissions was conducted from 1 January 2008 to 31 December 2017. Hospital admissions for patients with a diagnosis of cirrhosis were categorised by the presence or absence of sepsis/bacteraemia. Clinical and sociodemographic information including cirrhosis aetiology, complications and comorbidities, and in-hospital mortality were examined using bivariate and multivariate analyses. In patients with bacteraemia, the type and prevalence of bacteria and antibiotic resistance was assessed.ResultsSepsis/bacteraemia was present in 3951 of 103 165 hospital admissions with a diagnosis of cirrhosis. Factors associated with sepsis/bacteraemia included disease aetiology, particularly primary sclerosing cholangitis (adj-OR 15.09, 95% CI 12.24 to 18.60), alcohol (adj-OR 2.90, 95% CI 2.71 to 3.09), Charlson Comorbidity Index ≥3 (adj-OR 3.54, 95% CI 3.19 to 3.93) and diabetes (adj-OR 1.87, 95% CI 1.74 to 2.01). Overall case-fatality rate among admissions with sepsis/bacteraemia was 27.7% (95% CI 26.3% to 29.1%) vs 3.7% (95% CI 3.6% to 3.8%) without sepsis/bacteraemia. In-hospital death was significantly associated with sepsis/bacteraemia (adj-OR 6.50, 95% CI 5.95 to 7.11). The most common organisms identified were Escherichia coli and Staphylococcus aureus, present in 22.9% and 18.1%, respectively, of the 2265 admissions with a positive blood culture. The prevalence of MDR bacteria was low (5.6%)ConclusionMorbidity and mortality related to sepsis/bacteraemia in patients with cirrhosis remains a critical clinical problem.


2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 637-643
Author(s):  
Jennifer A Neff ◽  
Danir F Bayramov ◽  
Esha A Patel ◽  
Jing Miao

ABSTRACT Introduction Infection frequently complicates the treatment of combat-related wounds, impairs healing, and leads to worse outcomes. To better manage wound infections, antimicrobial therapies that are effective against biofilm and designed for direct wound application are needed. The primary objective of this work was to evaluate a chitosan matrix for delivery of two engineered antimicrobial peptides, (ASP)-1 and ASP-2, to treat biofilm-associated bacteria. A secondary objective was to determine whether replacing the levorotatory (L) form amino acids in ASP-2 with dextrorotatory (D) form amino acids would impact peptide activity. Materials and Methods Chitosan gels loaded with antimicrobial peptides were evaluated for peptide release over 7 days and tested for efficacy against biofilms grown both in vitro on polymer mesh and ex vivo on porcine skin. Results When delivered via chitosan, 70% to 80% of peptides were released over 7 days. Gels eradicated biofilms of gram-positive and gram-negative, drug-resistant bacteria in vitro and ex vivo. Under the conditions tested, no meaningful differences in peptide activity between the L and D forms of ASP-2 were detected. Conclusions Chitosan serves as an effective delivery platform for ASP-1 and ASP-2 to treat biofilm-embedded bacteria and warrants further development as a topical treatment.


2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Rahmawati Rahmawati ◽  
Trimayasari Trimayasari ◽  
Ghozali Akhmad Mustaqim ◽  
Wening Dwi Prastiwi ◽  
Emas Agus Prastyo Wibowo

AbstractSoap facial cleanser is needed to keep the facial skin to keep them clean and healthy. The purpose of this study to make soap cleanser with natural materials such as hard water deposits leri. This is because the use of leri water starch or starch granules of fine particles contained in water leri dansel dust can shed the dead skin on the face because of the essential amino acids contained can regenerate skin cells. In addition, water leri can brighten the face because the leri water oryzanol contain substances that can update the development and formation of the pigment melanin, which is effectively to ward off ultraviolet rays. The process of making soap using the principle of saponification reaction, namely the reaction between the oil and the KOH/NaOH. Facial cleansing soap made in this study is solid soap. Based on the results of quality test, soap solid leri water has a pH of 11.1, saponification number is 33, the water content of 46% as well as respondents to the test aspects of aroma and foam shows good results so this water leri treatment can be an alternative solution to prevent the use of soap facial cleansers that contain harmful chemicals. Keywords: air leri, soap cleanser, saponification  AbstrakSabun pembersih wajah sangat diperlukan untuk menjaga kulit wajah agar tetap bersih dan sehat. Tujuan dari penelitian ini untuk membuat sabun pembersih wajah dengan bahan alami berupa endapan air leri. Penggunaan air leri ini dikarenakan butiran partikel starch atau pati halus yang terdapat dalam air leri dapat merontokkan debu dansel kulit mati pada wajah karena asam amino esensial yang terkandung dapat meregenerasi sel-sel kulit. Selain itu, air leri dapat mencerahkan wajah karena air leri mengandung zat oryzanol yang dapat memperbarui perkembangan dan pembentukan pigmen melanin, yang efektif guna menangkal sinar ultraviolet. Proses pembuatan sabun menggunakan prinsip reaksi saponifikasi, yaitu reaksi antara minyak dan KOH/NaOH. Sabun pembersih wajah yang dibuat dalam penelitian ini ialah sabun padat. Berdasarkan hasil uji mutu, sabun air leri padat memiliki pH 11,1, angka penyabunan sebesar 33 kadar air 46 kadar air 46 % serta uji responden terhadap aspek aroma dan busa yang menunjukkan hasil cukup baik sehingga pengolahan air leri ini dapat menjadi solusi alternative untuk mencegah penggunaan sabun pembersih wajah yang mengandung bahan kimia berbahaya. Kata kunci: air leri, sabun pembersih wajah, saponifikasi 


2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.


2020 ◽  
Vol 2 (1) ◽  
pp. 32-55
Author(s):  
Natalia Christofoletti Barrenha
Keyword(s):  
The Face ◽  

This text seeks to explore the Argentine films Castro (Alejo Moguillansky, 2009) and El asaltante (Pablo Fendrik, 2007) from within the displacement of their characters through the city. This transit configures the organising element of the plots, determining the direction and rhythm of events. The escape motto will structure the film analyses, which are also twinned by the sensory apprehension that comes from the spaces they travel through. The notion of escape, as explored by Esteban Dipaola in Argentine cinema of the 1990s, continues to throb in mid-to-late 2000s production, and in these films represents the means by which the protagonists deploy critical attitudes—sometimes radical and explosive, sometimes silent—in the face of fixed notions, suggesting some scepticism about the “stability” and “order” that they (dis)encounter in normality. RESUMEN Este texto busca explorar los largometrajes argentinos Castro (Alejo Moguillansky, 2009) y El asaltante (Pablo Fendrik, 2007) a partir del desplazamiento de sus personajes por la ciudad. El transitar se configura como elemento organizador de las tramas, determinando la dirección y el ritmo de los acontecimientos. El tema de la fuga irá estructurando los análisis de las películas, las cuales también están relacionadas por la aprehensión sensorial que hacen de los espacios que recorren. La noción de fuga, tal y como fue explorada por Esteban Dipaola en el cine argentino de los años 90, continúa vigente en la producción de mediados/fines de la primera década del siglo XXI, y en estas películas es el recurso por medio del cual los protagonistas despliegan actitudes críticas – a veces radicales y explosivas, y a veces silenciosas – frente a nociones convencionales, lo cual hace pensar que existe un cierto escepticismo con relación a la “estabilidad” y al “orden” que ellos (des)encuentran en la normalidad. RESUMO Este texto busca explorar os longas-metragens argentinos Castro (Alejo Moguillansky, 2009) e El asaltante (Pablo Fendrik, 2007) a partir do deslocamento de seus personagens pela cidade. O transitar configura-se como elemento organizador das tramas, determinando a direção e o ritmo dos acontecimentos. O mote da fuga estruturará as análises dos filmes, os quais também se irmanam pela apreensão sensorial que fazem dos espaços que percorrem. A noção de fuga, conforme explorada por Esteban Dipaola no cinema argentino da década de 1990, continua a pulsar na produção de meados/fins dos anos 2000, e é, nestes filmes, o recurso através do qual os protagonistas desdobram atitudes críticas – às vezes radicais e explosivas, às vezes silenciosas – diante de noções fixas, sugerindo certo ceticismo em relação à “estabilidade” e à “ordem” que eles (des)encontram na normalidade.


2018 ◽  
Vol 2 (4) ◽  
pp. 46-59
Author(s):  
A.G. Salmanov ◽  
O.M. Verner ◽  
L.F. Slepova

Species of the Acinetobacter represent opportunistic bacteria with a growing clinical significance for Healthcare-associated infections (HAIs). In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe taxonomy, pathogenicity, and antibiotic resistance of these bacteria. Pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial  infections  are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance to antibiotics as well as identification of Acinetobacter.


2020 ◽  
Vol 70 (12) ◽  
pp. 4287-4294

Cancer is the second leading cause of death in Romania and worldwide. Cancer patients are at increasing risk of acquiring bacterial infection with multi-resistant germs, including multidrug-resistant (MDR) strains of Gram-negative bacteria involved in nosocomial infection. Romania is one of the South-Eastern European countries with one of the highest prevalence rates of MDR pathogens. To determine the resistance pattern of bacterial profile and antibiotic resistance pattern in cancer patients admitted at the County Emergency Clinical Hospital Craiova, Romania. A retrospective study of bacterial pathogens was carried out on 90 adult cancer patients admitted from January to December 2018. The analysis of the resistance patterns for the action of the appropriate antibiotics was performed using Vitek 2 Compact system and diffusion method. In this study there were analysed 92 samples from 90 oncological patients (37-86 years). A total of 157 bacterial isolates were obtained, of which 37 strains of Staphylococcus aureus (23.56%), followed by Streptococcus pneumoniae (23- 14.64%), Klebsiella spp. and Escherichia coli (22 - 14,01%). The most common isolates were from respiratory tract (86 isolates - 54.77%). High rates of MDR were found for E. coli (63.63%), MRSA (61,11%) and Klebsiella spp. (54,54%), while one third of the isolated strains of Pseudomonas aeruginosa, Acinetobacter spp. and Proteus spp. were MDR. The findings of this study may be the basis for further more extensive studies highlighting the germs involved in the infectious pathology of cancer patients, in order to determine the antimicrobial resistance and to improve the methods of prophylaxis and treatment. Keywords: multidrug resistance (MDR), cancer patients, bacterial pathogen


2020 ◽  
Vol 20 (14) ◽  
pp. 1264-1273 ◽  
Author(s):  
Bruno Casciaro ◽  
Floriana Cappiello ◽  
Walter Verrusio ◽  
Mauro Cacciafesta ◽  
Maria Luisa Mangoni

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.


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