Proline-rich antimicrobial peptide Api137 is bactericidal in porcine blood infected ex vivo with a porcine or human Klebsiella pneumoniae strain

Krieger, Ann-Kathrin; Knappe, Daniel; Öhlmann, Sophie; Mayer, Leonie; Eder, Ines; Köller, G.; Hoffmann, Ralf; Rieckmann, Karoline; Baums, Christoph Georg

doi:10.1016/j.jgar.2020.12.012

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…All PrAMPs tested, including the reverse and scrambled peptides, showed no significant hemolytic activity compared to the untreated control (addition of PBS) up to concentrations of 600 mg/L (234 to 285 μmol/L), as previously reported for some PrAMPs (Czihal et al, 2012;Krieger et al, 2021;Mohammed et al, 2023), in contrast to a strong hemolytic effect observed for amphotericin B already at the lowest concentration tested (125 mg/L; 135 μmol/L) (Supplementary Figure S5).…”

Section: Cytotoxicity and Hemolytic Activitysupporting

confidence: 76%

Evaluation of proline-rich antimicrobial peptides as potential lead structures for novel antimycotics against Cryptococcus neoformans

Brakel,

Grochow,

Fritsche

et al. 2024

Front. Microbiol.

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BackgroundCryptococcosis and cryptococcal meningitis, caused by Cryptococcus neoformans infections, lead to approximately 180,000 deaths per year, primarily in developing countries. Individuals with compromised immune systems, e.g., due to HIV infection (AIDS) or chemotherapy, are particularly vulnerable. Conventional treatment options are often limited and can cause severe side effects. Therefore, this study aimed to investigate the antifungal effect of insect-derived proline-rich antimicrobial peptides (PrAMPs) against C. neoformans. These peptides are known for their low toxicity and their high efficacy in murine infection models, making them a promising alternative for treatment.ResultsA preliminary screening of the minimal inhibitory concentrations (MICs) of 20 AMPs, including the well-known PrAMPs Onc112, Api137, and Chex1Arg20 as well as the cathelicidin CRAMP against the C. neoformans strains 1841, H99, and KN99α revealed promising results, with MICs as low as 1.6 μmol/L. Subsequent investigations of selected peptides, determining their influence on fungal colony-forming units, confirmed their strong activity. The antifungal activity was affected by factors such as peptide net charge and sequence, with stronger effects at higher net charges probably due to better intracellular uptake confirmed by confocal laser scanning microscopy. Inactive scrambled peptides suggest a specific intracellular target, although scanning electron microscopy showed that PrAMPs also damaged the cell exterior for a low proportion of the cells. Possible pore formation could facilitate entry into the cytosol.

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Section: Cytotoxicity and Hemolytic Activitysupporting

confidence: 76%

Evaluation of proline-rich antimicrobial peptides as potential lead structures for novel antimycotics against Cryptococcus neoformans

Brakel,

Grochow,

Fritsche

et al. 2024

Front. Microbiol.

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“…Sheep's milk has a high content of proline, which is involved in the synthesis of haemoglobin (Flis and Molik, 2021) and has "antibacterial" properties. The proline-rich "antimicrobial" peptide Api137 exerted a bactericidal effect in porcine blood infected ex vivo with porcine or human Klebsiella pneumonia strains (Krieger et al, 2021). In human nutrition, milk and dairy products are the primary sources of fat-soluble vitamins.…”

Section: Immune Stimulationmentioning

confidence: 99%

The role of sheep’s milk bioactive substances in the prevention of metabolic and viral diseases

Flis¹,

Szczecina²,

Molik³

2022

J. Anim. Feed Sci.

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“…As part of well-established peptide antibiotics, such as the glycopeptide vancomycin [6] and the cationic cyclic polymyxins [7], several bioactive peptides targeting different cellular components have been identified and studied as novel antibacterial drugs. For instance, apidaecin (Api137) is a peptide extracted from honeybees and targets the ribosome [8,9]. Murepavidin is a peptidomimetic that interacts with the bacterial lipopolysaccharide transport protein LptD [10,11].…”

Section: Introductionmentioning

confidence: 99%

Peptaibol Analogs Show Potent Antibacterial Activity against Multidrug Resistant Opportunistic Pathogens

Torre

Sannio

Battistella

et al. 2023

IJMS

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New classes of antibacterial drugs are urgently needed to address the global issue of antibiotic resistance. In this context, peptaibols are promising membrane-active peptides since they are not involved in innate immunity and their antimicrobial activity does not involve specific cellular targets, therefore reducing the chance of bacterial resistance development. Trichogin GA IV is a nonhemolytic, natural, short-length peptaibol active against Gram-positive bacteria and resistant to proteolysis. In this work, we report on the antibacterial activity of cationic trichogin analogs. Several peptides appear non-hemolytic and strongly active against many clinically relevant bacterial species, including antibiotic-resistant clinical isolates, such as Staphylococcus aureus, Acinetobacter baumannii, and extensively drug-resistant Pseudomonas aeruginosa, against which there are only a limited number of antibiotics under development. Our results further highlight how the modification of natural peptides is a valuable strategy for obtaining improved antibacterial agents with potential therapeutic applications.

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Proline-rich antimicrobial peptide Api137 is bactericidal in porcine blood infected ex vivo with a porcine or human Klebsiella pneumoniae strain

Cited by 6 publications

References 40 publications

Evaluation of proline-rich antimicrobial peptides as potential lead structures for novel antimycotics against Cryptococcus neoformans

Evaluation of proline-rich antimicrobial peptides as potential lead structures for novel antimycotics against Cryptococcus neoformans

The role of sheep’s milk bioactive substances in the prevention of metabolic and viral diseases

Peptaibol Analogs Show Potent Antibacterial Activity against Multidrug Resistant Opportunistic Pathogens

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