scholarly journals Design of Novel Amphipathic α-Helical Antimicrobial Peptides with No Toxicity as Therapeutics against the Antibiotic-Resistant Gram-Negative Bacterial Pathogen, Acinetobacter Baumannii

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Mant CT ◽  
Jiang Z ◽  
Gera L ◽  
Davis T ◽  
Hodges RS
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Acinetobacter Baumannii ◽  
De Novo ◽  
Bacterial Pathogen ◽  
Polymyxin B ◽  
Hemolysis Assay ◽  
Charged Residues ◽  
Positively Charged ◽  
Specificity Determinants

We designed de novo and synthesized two series of five 26-residue amphipathic α-helical cationic antimicrobial peptides (AMPs) with five or six positively charged residues (D-Lys, L-Dab (2,4-diaminobutyric acid) or L-Dap (2,3-diaminopropionic acid)) on the polar face where all other residues are in the D-conformation. Hemolytic activity against human red blood cells was determined using the most stringent conditions for the hemolysis assay, 18h at 37°C, 1% human erythrocytes and peptide concentrations up to 1000 μg/mL (~380 μM). Antimicrobial activity was determined against 7 Acinetobacter baumannii strains, resistant to polymyxin B and colistin (antibiotics of last resort) to show the effect of positively charged residues in two different locations on the polar face (positions 3, 7, 11, 18, 22 and 26 versus positions 3, 7, 14, 15, 22 and 26). All 10 peptides had two D-Lys residues in the center of the non-polar face as “specificity determinants” at positions 13 and 16 which provide specificity for prokaryotic cells over eukaryotic cells. Specificity determinants also maintain excellent antimicrobial activity in the presence of human sera. This study shows that the location and type of positively charged residue (Dab and Dap) on the polar face are critical to obtain the best therapeutic indices.

scholarly journals Plant antimicrobial peptides: structures, functions, and applications

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Junpeng Li ◽  
Shuping Hu ◽  
Wei Jian ◽  
Chengjian Xie ◽  
Xingyong Yang
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Agricultural Production ◽  
Food Additives ◽  
Antimicrobial Activities ◽  
Gram Positive Bacteria ◽  
Potential Applications ◽  
Potential Applicability ◽  
Bacteria And Fungi ◽  
Positively Charged

AbstractAntimicrobial peptides (AMPs) are a class of short, usually positively charged polypeptides that exist in humans, animals, and plants. Considering the increasing number of drug-resistant pathogens, the antimicrobial activity of AMPs has attracted much attention. AMPs with broad-spectrum antimicrobial activity against many gram-positive bacteria, gram-negative bacteria, and fungi are an important defensive barrier against pathogens for many organisms. With continuing research, many other physiological functions of plant AMPs have been found in addition to their antimicrobial roles, such as regulating plant growth and development and treating many diseases with high efficacy. The potential applicability of plant AMPs in agricultural production, as food additives and disease treatments, has garnered much interest. This review focuses on the types of plant AMPs, their mechanisms of action, the parameters affecting the antimicrobial activities of AMPs, and their potential applications in agricultural production, the food industry, breeding industry, and medical field.

scholarly journals Novel Engineered Peptides of a Phage Lysin as Effective Antimicrobials against Multidrug-Resistant Acinetobacter baumannii

2016 ◽  
Vol 60 (5) ◽  
pp. 2671-2679 ◽  
Author(s):  
Mya Thandar ◽  
Rolf Lood ◽  
Benjamin Y. Winer ◽  
Douglas R. Deutsch ◽  
Chad W. Euler ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Pathogen ◽  
Antibacterial Activities ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Human Red Blood Cells ◽  
Phage Lysin

ABSTRACTAcinetobacter baumanniiis a Gram-negative bacterial pathogen responsible for a range of nosocomial infections. The recent rise and spread of multidrug-resistantA. baumanniiclones has fueled a search for alternative therapies, including bacteriophage endolysins with potent antibacterial activities. A common feature of these lysins is the presence of a highly positively charged C-terminal domain with a likely role in promoting outer membrane penetration. In the present study, we show that the C-terminal amino acids 108 to 138 of phage lysin PlyF307, named P307, alone were sufficient to killA. baumannii(>3 logs). Furthermore, P307 could be engineered for improved activity, the most active derivative being P307SQ-8C(>5-log kill). Both P307 and P307SQ-8Cshowed highin vitroactivity againstA. baumanniiin biofilms. Moreover, P307SQ-8Cexhibited MICs comparable to those of levofloxacin and ceftazidime and acted synergistically with polymyxin B. Although the peptides were shown to kill by disrupting the bacterial cytoplasmic membrane, they did not lyse human red blood cells or B cells; however, serum was found to be inhibitory to lytic activity. In a murine model ofA. baumanniiskin infection, P307SQ-8Creduced the bacterial burden by ∼2 logs in 2 h. This study demonstrates the prospect of using peptide derivatives from bacteriophage lysins to treat topical infections and remove biofilms caused by Gram-negative pathogens.

scholarly journals A Systematic Study of the Stability, Safety, and Efficacy of the de novo Designed Antimicrobial Peptide PepD2 and Its Modified Derivatives Against Acinetobacter baumannii

2021 ◽  
Vol 12 ◽  
Author(s):  
Sung-Pang Chen ◽  
Eric H-L Chen ◽  
Sheng-Yung Yang ◽  
Pin-Shin Kuo ◽  
Hau-Ming Jan ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
Acinetobacter Baumannii ◽  
De Novo ◽  
Multidrug Resistant ◽  
Hek293 Cells ◽  
Amino Acid Residues ◽  
Bacteria And Fungi ◽  
The Stability

Searching for new antimicrobials is a pressing issue to conquer the emergence of multidrug-resistant (MDR) bacteria and fungi. Antimicrobial peptides (AMPs) usually have antimicrobial mechanisms different from those of traditional antibiotics and bring new hope in the discovery of new antimicrobials. In addition to antimicrobial activity, stability and target selectivity are important concerns to decide whether an antimicrobial peptide can be applied in vivo. Here, we used a simple de novo designed peptide, pepD2, which contains only three kinds of amino acid residues (W, K, L), as an example to evaluate how the residues and modifications affect the antimicrobial activity against Acinetobacter baumannii, stability in plasma, and toxicity to human HEK293 cells. We found that pepI2 with a Leu→Ile substitution can decrease the minimum bactericidal concentrations (MBC) against A. baumannii by one half (4 μg/mL). A D-form peptide, pepdD2, in which the D-enantiomers replaced the L-enantiomers of the Lys(K) and Leu(L) residues, extended the peptide half-life in plasma by more than 12-fold. PepD3 is 3-residue shorter than pepD2. Decreasing peptide length did not affect antimicrobial activity but increased the IC50 to HEK293 cells, thus increased the selectivity index (SI) between A. baumannii and HEK293 cells from 4.7 to 8.5. The chain length increase of the N-terminal acyl group and the Lys→Arg substitution greatly enhanced the hemolytic activity, hence those modifications are not good for clinical application. Unlike colistin, the action mechanism of our peptides relies on negatively charged lipids rather than lipopolysaccharides. Therefore, not only gram-negative bacteria but also gram-positive bacteria can be killed by our peptides.

scholarly journals Antimicrobial Activity of Selected Antimicrobial Peptides Against Planktonic Culture and Biofilm of Acinetobacter baumannii

2018 ◽  
Vol 11 (1) ◽  
pp. 317-324 ◽  
Author(s):  
Maciej Jaśkiewicz ◽  
Damian Neubauer ◽  
Kamil Kazor ◽  
Sylwia Bartoszewska ◽  
Wojciech Kamysz
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Acinetobacter Baumannii ◽  
Reference Strain ◽  
Inhibitory Concentration ◽  
Wide Spectrum ◽  
Selectivity Index ◽  
Planktonic Culture

Abstract Acinetobacter baumannii is one of the most challenging pathogens, on account of its predisposition to develop resistance leading to severe, difficult-to-treat infections. As these bacteria are more usually isolated from nosocomial infections, the new therapeutic options are demanded. Antimicrobial peptides (AMPs) are compounds likely to find application in the treatment of A. baumannii. These compounds exhibit a wide spectrum of antimicrobial activity and were found to be effective against biofilm. In this study, eight AMPs, namely aurein 1.2, CAMEL, citropin 1.1., LL-37, omiganan, r-omiganan, pexiganan, and temporin A, were tested for their antimicrobial activity. A reference strain of A. baumannii ATCC 19606 was used. Antimicrobial assays included determination of the minimum inhibitory concentration and the minimum biofilm eradication concentration. Considering the fact that the majority of A. baumannii infections are associated with mechanical ventilation and the use of indwelling devices, the activity against biofilm was assessed on both a polystyrene surface and tracheal tube fragments. In addition, cytotoxicity (HaCaT) was determined and in vitro selectivity index was calculated.

scholarly journals Detection of OXA Beta Lactamases Among Clinical Isolates of Acinetobacter baumannii Isolated from Tehran Hospitals, Iran

2019 ◽  
Vol 13 (1) ◽  
pp. 68-72
Author(s):  
Reza Ranjbar ◽  
Shahin Zayeri ◽  
Davoud Afshar ◽  
Shohreh Farshad
Keyword(s):  
Acinetobacter Baumannii ◽  
Early Recognition ◽  
Bacterial Pathogen ◽  
Polymyxin B ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Diffusion Method ◽  
Disk Diffusion Method ◽  
Molecular Tests ◽  
High Level

Background and Objective:Acinetobacter baumanniiis a non-motile Gram-negative bacterial pathogen with the history of vast resistant to antibiotics. The aim of this study was to determine the possibility of existence of OXAs genes among clinical isolates ofA. baumanniiobtained from Tehran hospitals.Materials and Methods:A total of 101 isolates were identified asA. baumanniiby common biochemical and molecular tests. The susceptibility to different antibiotics was assessed with Kirby-Bauer disk diffusion method. Phenotypic Detection of MBLs was performed with CDT test and PCR assay was also performed for detection ofblaOXA-23-like,blaOXA-24-like,blaOXA-40-like,blaOXA-51-like,blaOXA-58-likeandblaOXA-143-likegenesResults:All isolates ofA. baumanniishowed high-level of resistance to all antibiotics except for Polymyxin B. TheblaOXA-51 likegenes was found in all of the isolates and the prevalence ofblaOXA-143like,blaOXA-23like,blaOXA-40likeandblaOXA-24likewere 56%, 45.45%, 33% and 11.8%, respectively.Conclusion:TheblaOXA-51-likewas the predominant mechanism of resistance to imipenem inA. baumanniiand therefore, early recognition of carbapenem-resistantA. baumanniiisolates is a useful tools to prevent their spreading within the hospital environment.

scholarly journals De Novo Design of Antimicrobial Peptides With a Special Charge Pattern and Their Application in Combating Plant Pathogens

2021 ◽  
Vol 12 ◽  
Author(s):  
Eric H. -L. Chen ◽  
Cheng-Wei Weng ◽  
Yi-Min Li ◽  
Ming-Chin Wu ◽  
Chien-Chih Yang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Plant Pathogens ◽  
De Novo ◽  
Plant Protection ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Plant Diseases ◽  
Basic Residue ◽  
Wide Range

Plant diseases are important issues in agriculture, and the development of effective and environment-friendly means of disease control is crucial and highly desired. Antimicrobial peptides (AMPs) are known as potential alternatives to chemical pesticides because of their potent broad-spectrum antimicrobial activity and because they have no risk, or have only a low risk, of developing chemical-resistant pathogens. In this study, we designed a series of amphipathic helical peptides with different spatial distributions of positive charges and found that the peptides that had a special sequence pattern “BBHBBHHBBH” (“B” for basic residue and “H” for hydrophobic residue) displayed excellent bactericidal and fungicidal activities in a wide range of economically important plant pathogens. The peptides with higher helical propensity had lower antimicrobial activity. When we modified the peptides with a long acyl chain at their N-terminus, their plant protection effect improved. Our application of the fatty acyl-modified peptides on the leaves of tomato and Arabidopsis plants lessened the infection caused by Pectobacterium carotovorum subsp. carotovorum and Botrytis cinerea. Our study provides important insights on the development of more potent novel AMPs for plant protection.

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