Molecules, Vol. 24, Pages 2987: Replacement of l-Amino Acids by d-Amino Acids in the Antimicrobial Peptide Ranalexin and Its Consequences for Antimicrobial Activity and Biodistribution

Molecules, Vol. 24, Pages 2987: Replacement of l-Amino Acids by d-Amino Acids in the Antimicrobial Peptide Ranalexin and Its Consequences for Antimicrobial Activity and Biodistribution Molecules doi: 10.3390/molecules24162987 Authors: Cornelius Domhan Philipp Uhl Christian Kleist Stefan Zimmermann Florian Umstätter Karin Leotta Walter Mier Michael Wink Infections caused by multidrug-resistant bacteria are a global emerging problem. New antibiotics that rely on innovative modes of action are urgently needed. Ranalexin is a potent antimicrobial peptide (AMP) produced in the skin of the American bullfrog Rana catesbeiana. Despite strong antimicrobial activity against Gram-positive bacteria, ranalexin shows disadvantages such as poor pharmacokinetics. To tackle these problems, a ranalexin derivative consisting exclusively of d-amino acids (named danalexin) was synthesized and compared to the original ranalexin for its antimicrobial potential and its biodistribution properties in a rat model. Danalexin showed improved biodistribution with an extended retention in the organisms of Wistar rats when compared to ranalexin. While ranalexin is rapidly cleared from the body, danalexin is retained primarily in the kidneys. Remarkably, both peptides showed strong antimicrobial activity against Gram-positive bacteria and Gram-negative bacteria of the genus Acinetobacter with minimum inhibitory concentrations (MICs) between 4 and 16 mg/L (1.9–7.6 &mic...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research

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While the antibiotic era has come and gone, antimicrobial peptides (AMPs) hold promise as novel therapies to treat multidrug resistant (MDR) pathogens in an age where the threat of multidrug resistance escalates worldwide. Here, we report the bactericidal properties of NuriPep 1653, a novel 22 mer and non-modified peptide. NuriPep 1653 was identified within the sequence of the non-antimicrobial P54 protein, which is involved in nutrient reservoir activity in Pisum sativum. Total bacterial clearance of Acinetobacter baumannii cells (1 × 108 cells/mL) was observed using only 4 × MIC (48 μg/mL) of NuriPep 1653 ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Acinetobacter calcoaceticus-Acinetobacter baumannii complex is considered one of the main causes of hospital-acquired infections. Acinetobacter seifertii was recently characterized within this complex and it has been described as an emergent pathogen associated with bacteremia. The emergence of multidrug-resistant (MDR) bacteria, including Acinetobacter sp., is considered a global public health threat and an environmental problem because MDR bacteria have been spreading from several sources. Therefore, this study aimed to characterize an environmental MDR A. seifertii isolate (SAb133) using whole genome sequencing and a co...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
ConclusionThe prevalence of MDR-GNB in Iranian burn patients is very high. Thus, a comprehensive infectious control programme, a reduction in the use of antibiotic prophylaxis, and thorough information regarding antimicrobial resistance patterns is required.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
ConclusionThis is the first report of the genome sequence of an A. baumannii ST1928 clinical isolate carrying a novel class C β-lactamase gene from China. The genome sequence data can be used as a reference sequence for comparative studies and would facilitate further understanding of the antimicrobial resistance mechanisms of A. baumannii at the genomic level.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
CONCLUSIONS: Our study reports, for the first time, the emergence of plasmid-mediated mcr-1-encoded colistin resistance in multidrug resistant strains of A. baumannii and P. aeruginosa. Further large scales studies are recommended to investigate the prevalence of this mode of resistance in these highly pathogenic bacteria.
Source: Revista da Sociedade Brasileira de Medicina Tropical - Category: Tropical Medicine Source Type: research
In conclusion, mcr-1-positive E. coli environmental isolates were mostly characterised by positive for APEC-associated virulence genes. Co-presence of those genes may suggest the existence of common source in animals and/or their associated environments.IMPORTANCE Colistin is considered as a last-line therapeutic option in severe infections due to multidrug-resistant Gram-negative bacteria, in particular carbapenemase-producing Enterobacteriaceae and multidrug-resistant Acinetobacter baumannii Increasing prevalence of mcr genes in diverse Enterobacteriaceae species, mainly E. coli and Klebsiella pneumoniae from humans and ...
Source: Applied and Environmental Microbiology - Category: Microbiology Authors: Tags: Appl Environ Microbiol Source Type: research
Members of the Acinetobacter baumannii-calcoaceticus complex are nosocomial pathogens frequently causing multidrug-resistant infections that are increasing at alarming rates. A. baumannii has become the Gram-negative bacterium with the highest rate of multidrug resistance. As such, it is categorized by the World Health Organization as a critical priority for the research and development of new antimicrobial therapies. The zinc-dependent metalloendopeptidase CpaA is a predominant substrate of the type II secretion system (T2SS). CpaA is also a virulence factor of medically relevant Acinetobacter strains that specifically de...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Microbiology Source Type: research
Discussion: The infection rate in our centre compared to previous studies of comparable patients was matching. Effective management of postoperative infections should be considered, and identified risk factors in this study can help to focus on effective prevention and treatment strategies. PMID: 31467552 [PubMed]
Source: International Journal of Microbiology - Category: Microbiology Tags: Int J Microbiol Source Type: research
Abstract Candida auris is an emerging pathogenic yeast responsible for nosocomial infections with high mortality, on a global scale. A 65-year-old woman with hypovolemic shock and severe metabolic acidosis was intubated and admitted to the intensive care unit (ICU). Shortly after admission, she developed ventilator-associated pneumonia caused by multidrug-resistant Acinetobacter baumannii, which necessitated treatment with high-dose ampicillin-sulbactam. Two weeks later, a yeast was cultured from her blood. It formed pale pink colonies on CHROMagar Candida medium and produced predominantly oval budding yeast cells...
Source: Annals of Clinical and Laboratory Science - Category: Laboratory Medicine Authors: Tags: Ann Clin Lab Sci Source Type: research
Purpose of review To describe recent data about Acinetobacter baumannii pneumonia epidemiology and the therapeutic options including adjunctive nebulized therapy. Recent findings A. baumannii is a major cause of nosocomial pneumonia in certain geographic areas affecting mainly debilitated patients, with prolonged hospitalization and broad-spectrum antimicrobials. Inappropriate empirical treatment has clearly been associated with increased mortality in A. baumannii pneumonia. Carbapenems may not be considered the treatment of choice in areas with high rates of carbapenem-resistant A. baumannii. Nowadays, polymyxins are...
Source: Current Opinion in Critical Care - Category: Nursing Tags: SEVERE INFECTIONS: Edited by Michael S. Niederman Source Type: research
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