Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action

Drayton, Matthew; Deisinger, Julia P.; Ludwig, Kevin C.; Raheem, Nigare; Müller, Anna; Schneider, Tanja; Straus, Suzana K.

doi:10.3390/ijms222011172

Cited by 60 publications

(51 citation statements)

References 142 publications

(198 reference statements)

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“…In this study, we found that CATH-1, CATH-3, and PMAP-36 had a synergistic effect with erythromycin on bacterial killing and significantly reduced resistance to antibiotics. It has been reported that the bactericidal mechanism of AMPs acts through the cell membrane not involved in a specific target, so it is unlikely to develop microbial resistance (Drayton et al, 2021). Our study showed that AMPs (CATH-1,−3 and PMAP-36) have good bactericidal activities against S. aureus, S. enteritidis, and E. coli, which is consistent with other findings that CATH-1,−3 and PMAP-36 showed a broad spectrum of bactericidal activities against S. aureus, S. enteritidis, E. coli, Campylobacter jejuni, and Clostridium perfringens (Lv et al, 2014;Nguyen et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens

et al. 2022

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With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternative to enhance antibacterial efficiency. In this study, we investigated the synergistic bactericidal effect of AMPs, including chicken (CATH-1,−2,−3, and -B1), mice (CRAMP), and porcine (PMAP-36 and PR-39) in combination with conventional antibiotics containing ampicillin, tetracycline, gentamicin, and erythromycin against Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. The results showed that the minimum bactericidal concentration (MBC) of CATH-1,−3 and PMAP-36 was lower than 10 μM, indicating that these three AMPs had good bacterial activity against S. aureus, S. enteritidis, and E. coli. Then, the synergistic antibacterial activity of AMPs and antibiotics combination was determined by the fractional bactericidal concentration index (FBCI). The results showed that the FBCI of AMPs (CATH-1,−3 and PMAP-36) and erythromycin was lower than 0.5 against bacterial pathogens, demonstrating that they had a synergistic bactericidal effect. Furthermore, the time-killing kinetics of AMPs (CATH-1,−3 and PMAP-36) in combination with erythromycin showed that they had a continuous killing effect on bacteria within 3 h. Notably, the combination showed lower hemolytic activity and cytotoxicity to mammal cells compared to erythromycin and peptide alone treatment. In addition, the antibacterial mechanism of CATH-1 and erythromycin combination against E. coli was studied. The results of the scanning electron microscope showed that CATH-1 enhanced the antibacterial activity of erythromycin by increasing the permeability of bacterial cell membrane. Moreover, the results of bacterial migration movement showed that the combination of CATH-1 and erythromycin significantly inhibits the migration of E. coli. Finally, drug resistance analysis was performed and the results showed that CATH-1 delayed the emergence of E. coli resistance to erythromycin. In conclusion, the combination of CATH-1 and erythromycin has synergistic antibacterial activity and reduces the emergence of bacterial drug resistance. Our study provides valuable information to develop AMPs as potential substitutes or adjuvants for traditional antibiotics.

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Section: Discussionmentioning

confidence: 99%

Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens

et al. 2022

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“…The promising future development path of AMPs as new therapeutics is to create multifunctional AMPs by combining their direct antimicrobial activity with indirect activity, e.g., modulation of the immune system response. Immunomodulation can enhance the antimicrobial effects of AMPs by inducing the recruitment of antigen-presenting cells to the site of infection, activating neutrophils or macrophages, influencing the differentiation of dendritic cells, and suppressing pro-inflammatory cytokines [ 16 , 28 , 29 , 30 ]. Anti-infective therapeutic peptides with combined antimicrobial and immunomodulatory properties represent a new approach to treat antibiotic-resistant infections.…”

Section: De Novo Designed Antimicrobial Immunomodulatory Peptidesmentioning

confidence: 99%

Synthetic Antimicrobial Immunomodulatory Peptides: Ongoing Studies and Clinical Trials

Lesiuk¹,

Paduszynska

Greber

2022

Antibiotics

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The increasingly widespread antimicrobial resistance forces the search for new antimicrobial substances capable of fighting infection. Antimicrobial peptides (AMPs) and their synthetic analogs form an extensive group of compounds of great structural diversity and multifunctionality, different modes of antimicrobial action, and considerable market potential. Some AMPs, in addition to their proven antibacterial, antifungal, and antiviral activity, also demonstrate anti-inflammatory and immunomodulatory capabilities; these are called innate defense regulator (IDR) peptides. IDR peptides stimulate or inhibit the body’s immune system, e.g., by stimulating leukocyte migration to the site of infection, driving macrophage differentiation and activation, providing chemotactic action for neutrophils, degranulation and activation of mast cells, altering chemokine and cytokine production, and even induction of angiogenesis and wound healing. Such multifunctional immunomodulatory peptide molecules are currently being investigated and developed. Exploring and utilizing IDR peptides as an indirect weapon against infectious diseases could represent a completely new strategy to cope with the issue of antimicrobial resistance.

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“…In the era of bacterial AMR and the drying pipelines of new small molecule antibiotics, antimicrobial peptides (AMPs) provide certain hopes to fight against MDR pathogens [14][15][16]. AMPs, also termed as host defense peptides (HDPs), are evolutionarily conserved arsenals of all organisms to fend microbial invasion [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

Bhattacharjya

Mohid

Bhunia

2022

IJMS

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Global rise of infections and deaths caused by drug-resistant bacterial pathogens are among the unmet medical needs. In an age of drying pipeline of novel antibiotics to treat bacterial infections, antimicrobial peptides (AMPs) are proven to be valid therapeutics modalities. Direct in vivo applications of many AMPs could be challenging; however, works are demonstrating encouraging results for some of them. In this review article, we discussed 3-D structures of potent AMPs e.g., polymyxin, thanatin, MSI, protegrin, OMPTA in complex with bacterial targets and their mode of actions. Studies on human peptide LL37 and de novo-designed peptides are also discussed. We have focused on AMPs which are effective against drug-resistant Gram-negative bacteria. Since treatment options for the infections caused by super bugs of Gram-negative bacteria are now extremely limited. We also summarize some of the pertinent challenges in the field of clinical trials of AMPs.

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Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action

Cited by 60 publications

References 142 publications

Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens

Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens

Synthetic Antimicrobial Immunomodulatory Peptides: Ongoing Studies and Clinical Trials

Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

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