Structure-Dependent Immune Modulatory Activity of  Protegrin-1 Analogs

Zughaier, Susu M.; Svoboda, Pavel; Pohl, Jan

doi:10.3390/antibiotics3040694

Cited by 6 publications

(4 citation statements)

References 87 publications

(96 reference statements)

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“…The presence of the disulfide bonds is required to maintain potent antimicrobial activity [11] . PG‐1 has been shown to disrupt anionic bacterial membranes and biofilms, showing also a wide range of in vivo immunomodulatory properties like inhibition of LPS and increasing neutrophil clearance [6b,c] . This distinct antimicrobial mechanism of action of PG‐1 limits potential cross‐resistance while providing synergy in combination with other locally produced host defense peptides and/or conventional antibiotics [6d] .…”

Section: Introductionmentioning

confidence: 99%

Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity

Rajasekaran

Dughbaj

Ramirez

et al. 2021

Chemistry A European J

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The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to the rapid development of drug resistance to current antibiotic therapeutics. Respiratory failure and septicemia are the leading causes of mortality among hospitalized patients. Here, the development of a novel engineered cyclotide with effective broad-spectrum antibacterial activity against several ESKAPE bacterial strains and clinical isolates is reported. The most active antibacterial cyclotide was extremely stable in serum, showed little hemolytic activity, and provided protection in vivo in a murine model of P. aeruginosa peritonitis. These results highlight the potential of the cyclotide scaffold for the development of novel antimicrobial therapeutic leads for the treatment of bacteremia.

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Section: Introductionmentioning

confidence: 99%

Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity

Rajasekaran

Dughbaj

Ramirez

et al. 2021

Chemistry A European J

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“…Another example of a macrophage-modulating peptide is the cecropin A-magainin hybrid peptide, which decreased the production of nitric oxide and TNF-alpha by RAW 264.7 cells in response to E. coli LPS [ 94 ]. Protegrin 1 and analogues also inhibited macrophages’ inflammatory response to endotoxins and polysaccharides from Neisseria meningitidis, by decreasing IL-1beta, TNF-alpha and nitric oxide [ 95 ]. Interestingly, protegrin 1 retained this effect in the absence of one of the two native disulphide bridges, which are mandatory for the antimicrobial activity of this peptide [ 95 ].…”

Section: Other Peptides Other Bugsmentioning

confidence: 99%

“…Protegrin 1 and analogues also inhibited macrophages’ inflammatory response to endotoxins and polysaccharides from Neisseria meningitidis, by decreasing IL-1beta, TNF-alpha and nitric oxide [ 95 ]. Interestingly, protegrin 1 retained this effect in the absence of one of the two native disulphide bridges, which are mandatory for the antimicrobial activity of this peptide [ 95 ].…”

Section: Other Peptides Other Bugsmentioning

confidence: 99%

Immuno-Stimulatory Peptides as a Potential Adjunct Therapy against Intra-Macrophagic Pathogens

Silva

Gomes

2017

Molecules

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The treatment of infectious diseases is increasingly prone to failure due to the rapid spread of antibiotic-resistant pathogens. Antimicrobial peptides (AMPs) are natural components of the innate immune system of most living organisms. Their capacity to kill microbes through multiple mechanisms makes the development of bacterial resistance less likely. Additionally, AMPs have important immunomodulatory effects, which critically contribute to their role in host defense. In this paper, we review the most recent evidence for the importance of AMPs in host defense against intracellular pathogens, particularly intra-macrophagic pathogens, such as mycobacteria. Cathelicidins and defensins are reviewed in more detail, due to the abundance of studies on these molecules. The cell-intrinsic as well as the systemic immune-related effects of the different AMPs are discussed. In the face of the strong potential emerging from the reviewed studies, the prospects for future use of AMPs as part of the therapeutic armamentarium against infectious diseases are presented.

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“…To determine whether protegrine 1 (PG1), a peptide of 18 amino acids that belongs to the cathelicidin family of host defence peptides (Cho et al., ; Tamamura et al., ; Zughaier et al. , ) could replace antibiotics in semen extenders, we have analysed the effects of PG1 on sperm viability, as well as its effectiveness in controlling bacterial growth in boar seminal doses.…”

Section: Introductionmentioning

confidence: 99%

Effects of the antimicrobial peptide protegrine 1 on sperm viability and bacterial load of boar seminal doses

Sancho

Briz

Yeste

et al. 2017

Reprod Domestic Animals

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Contents The presence of bacteria adversely affects boar sperm quality of seminal doses intended for artificial insemination. Currently, the most common measure to prevent bacteriospermia is the addition of antibiotics in semen extenders; however, mounting evidence shows that microbial resistance exists. A promising alternative to replace antibiotics are antimicrobial peptides. In this study, the effects of the antimicrobial peptide protegrine 1 (PG1) on the sperm viability and bacterial load of boar seminal doses were evaluated. Three different concentrations of PG1 (2.5, 25 and 100 μg/ml) were tested over a storing period of 10 days at 17°C. Sperm viability was analysed by fluorescence microscopy (SYBR14/propidium iodide), and bacterial load was assessed by plating 100 μl of each sample in Luria–Bertani medium and incubated at 37°C for 72 hr under aerobic conditions. Protegrine 1 was effective in controlling the bacterial load in all the assessed concentrations (p < .05), reaching the lowest values at the highest concentrations of the antimicrobial peptide. Nevertheless, sperm viability was significantly (p < .05) reduced by all tested concentrations of this peptide, the most cytotoxic effects being observed at the highest PG1 concentrations. Despite these results, the use of PG1 as an alternative to antibiotics cannot be totally discarded, as further studies using the truncated form of this peptide are needed.

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Structure-Dependent Immune Modulatory Activity of Protegrin-1 Analogs

Cited by 6 publications

References 87 publications

Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity

Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity

Immuno-Stimulatory Peptides as a Potential Adjunct Therapy against Intra-Macrophagic Pathogens

Effects of the antimicrobial peptide protegrine 1 on sperm viability and bacterial load of boar seminal doses

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