Effects of N‐terminal modifications on the stability of antimicrobial peptide SAMP‐A4 analogues against protease degradation

2021 ◽  
Author(s):  
Ruifang Li ◽  
Songlin He ◽  
Kedong Yin ◽  
Beibei Zhang ◽  
Yanjie Yi ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
The Stability ◽  
Protease Degradation

scholarly journals Transient and Sustained Bacterial Adaptation following Repeated Sublethal Exposure to Microbicides and a Novel Human Antimicrobial Peptide

2014 ◽  
Vol 58 (10) ◽  
pp. 5809-5817 ◽  
Author(s):  
Sarah Forbes ◽  
Curtis B. Dobson ◽  
Gavin J. Humphreys ◽  
Andrew J. McBain
Keyword(s):  
Antimicrobial Peptide ◽  
Biofilm Formation ◽  
Bacterial Isolates ◽  
Exposure System ◽  
Polyhexamethylene Biguanide ◽  
Prevention And Treatment ◽  
Before And After ◽  
The Stability ◽  
Induced Changes ◽  
Laboratory Exposure

ABSTRACTMicrobicides (biocides) play an important role in the prevention and treatment of infections. While there is currently little evidence for in-use treatment failures attributable to acquired reductions in microbicide susceptibility, the susceptibility of some bacteria can be reduced by sublethal laboratory exposure to certain agents. In this investigation, a range of environmental bacterial isolates (11 genera, 18 species) were repeatedly exposed to four microbicides (cetrimide, chlorhexidine, polyhexamethylene biguanide [PHMB], and triclosan) and a cationic apolipoprotein E-derived antimicrobial peptide (apoEdpL-W) using a previously validated exposure system. Susceptibilities (MICs and minimum bactericidal concentrations [MBCs]) were determined before and after 10 passages (P10) in the presence of an antimicrobial and then after a further 10 passages without an antimicrobial to determine the stability of any adaptations. Bacteria exhibiting >4-fold increases in MBCs were further examined for alterations in biofilm-forming ability. Following microbicide exposure, ≥4-fold decreases in susceptibility (MIC or MBC) occurred for cetrimide (5/18 bacteria), apoEdpL-W (7/18), chlorhexidine (8/18), PHMB (8/18), and triclosan (11/18). Of the 34 ≥4-fold increases in the MICs, 15 were fully reversible, 13 were partially reversible, and 6 were nonreversible. Of the 26 ≥4-fold increases in the MBCs, 7 were fully reversible, 14 were partially reversible, and 5 were nonreversible. Significant decreases in biofilm formation in P10 strains occurred for apoEdpL-W (1/18 bacteria), chlorhexidine (1/18), and triclosan (2/18), while significant increases occurred for apoEdpL-W (1/18), triclosan (1/18), and chlorhexidine (2/18). These data indicate that the stability of induced changes in microbicide susceptibility varies but may be sustained for some combinations of a bacterium and a microbicide.

scholarly journals DEG9, a serine protease, modulates cytokinin and light signaling by regulating the level of ARABIDOPSIS RESPONSE REGULATOR 4

2016 ◽  
Vol 113 (25) ◽  
pp. E3568-E3576 ◽  
Author(s):  
Wei Chi ◽  
Jing Li ◽  
Baoye He ◽  
Xin Chai ◽  
Xiumei Xu ◽  
...  
Keyword(s):  
Serine Protease ◽  
Response Regulator ◽  
Light Signaling ◽  
Plant Signaling ◽  
Response Regulators ◽  
Cytokinin Signaling ◽  
Periplasmic Proteins ◽  
The Stability ◽  
Protease Degradation ◽  
Signaling Components

Cytokinin is an essential phytohormone that controls various biological processes in plants. A number of response regulators are known to be important for cytokinin signal transduction. ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4) mediates the cross-talk between light and cytokinin signaling through modulation of the activity of phytochrome B. However, the mechanism that regulates the activity and stability of ARR4 is unknown. Here we identify an ATP-independent serine protease, degradation of periplasmic proteins 9 (DEG9), which localizes to the nucleus and regulates the stability of ARR4. Biochemical evidence shows that DEG9 interacts with ARR4, thereby targeting ARR4 for degradation, which suggests that DEG9 regulates the stability of ARR4. Moreover, genetic evidence shows that DEG9 acts upstream of ARR4 and regulates the activity of ARR4 in cytokinin and light-signaling pathways. This study thus identifies a role for a ubiquitin-independent selective protein proteolysis in the regulation of the stability of plant signaling components.

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 D-amino acid substitution enhances the stability of antimicrobial peptide polybia-CP

2017 ◽  
Vol 49 (10) ◽  
pp. 916-925 ◽  
Author(s):  
Fengjing Jia ◽  
Jiayi Wang ◽  
Jinxiu Peng ◽  
Ping Zhao ◽  
Ziqing Kong ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antimicrobial Peptide ◽  
Amino Acid Substitution ◽  
The Stability

N‐terminal acetylation of antimicrobial peptide L163 improves its stability against protease degradation

2021 ◽  
Author(s):  
Dandan Li ◽  
Yanhui Yang ◽  
Ruifang Li ◽  
Liang Huang ◽  
Zichao Wang ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Protease Degradation

scholarly journals Cu2+ reduces hemolytic activity of the antimicrobial peptide HMPI and enhances its trypsin resistance

2020 ◽  
Vol 52 (6) ◽  
pp. 603-611
Author(s):  
Jinxiu Peng ◽  
Yang Yang ◽  
Ping Zhao ◽  
Shuai Qiu ◽  
Fengjing Jia ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antifungal Activity ◽  
Antimicrobial Peptide ◽  
Hemolytic Activity ◽  
Clinical Problem ◽  
Clinical Use ◽  
Drug Resistant ◽  
Oxygen Species ◽  
The Stability ◽  
Conventional Antibiotics

Abstract Nowadays, drug-resistant microbes are becoming a serious clinical problem threatening people’s health and life. Antimicrobial peptides (AMPs) are believed to be potential alternatives of conventional antibiotics to combat the threat of drug-resistant microbes. However, the susceptibility of AMPs toward proteases is one of the major problems limiting their clinical use. In the present study, we reported the effect of Cu2+ on the bioactivity of AMP HMPI. We found that the addition of Cu2+ could improve the protease resistance of AMP HMPI without affecting its bioactivity. Notably, after the binding of Cu2+ with HMPI, the hemolytic activity of HMPI was greatly decreased. In addition, our results also demonstrated that the addition of Cu2+ increased the production of reactive oxygen species in the fungal cells, which may be a supplement for the antifungal activity of HMPI. In conclusion, the introduction of Cu2+ may provide an inorganic strategy to improve the stability and decrease the hemolytic activity of AMP HMPI, while maintaining its antifungal activity.

scholarly journals Differential Protection of Cry1Fa Toxin against Spodoptera frugiperda Larval Gut Proteases by Cadherin Orthologs Correlates with Increased Synergism

2011 ◽  
Vol 78 (2) ◽  
pp. 354-362 ◽  
Author(s):  
Khalidur Rahman ◽  
Mohd Amir F. Abdullah ◽  
Suresh Ambati ◽  
Milton D. Taylor ◽  
Michael J. Adang
Keyword(s):  
Spodoptera Frugiperda ◽  
Membrane Vesicle ◽  
Resistance Management ◽  
Content Type ◽  
Development Of Resistance ◽  
Cry Toxin ◽  
Bt Toxins ◽  
The Stability ◽  
Protease Degradation

ABSTRACTThe Cry proteins produced byBacillus thuringiensis(Bt) are the most widely used biopesticides effective against a range of crop pests and disease vectors. Like chemical pesticides, development of resistance is the primary threat to the long-term efficacy of Bt toxins. Recently discovered cadherin-based Bt Cry synergists showed the potential to augment resistance management by improving efficacy of Cry toxins. However, the mode of action of Bt Cry synergists is thus far unclear. Here we elucidate the mechanism of cadherin-based Cry toxin synergism utilizing two cadherin peptides,Spodoptera frugiperdaCad (SfCad) andManduca sextaCad (MsCad), which differentially enhance Cry1Fa toxicity toSpodoptera frugiperdaneonates. We show that differential SfCad- and MsCad-mediated protection of Cry1Fa toxin in theSpodoptera frugiperdamidgut correlates with differential Cry1Fa toxicity enhancement. Both peptides exhibited high affinity for Cry1Fa toxin and an increased rate of Cry1Fa-induced pore formation inS. frugiperda. However, only SfCad bound theS. frugiperdabrush border membrane vesicle and more effectively prolonged the stability of Cry1Fa toxin in the gut, explaining higher Cry1Fa enhancement by this peptide. This study shows that cadherin fragments may enhanceB. thuringiensistoxicity by at least two different mechanisms or a combination thereof: (i) protection of Cry toxin from protease degradation in the insect midgut and (ii) enhancement of pore-forming ability of Cry toxin.

Sign in / Sign up

Export Citation Format

Share Document