Host Defense Peptides: Immune Modulation and Antimicrobial Activity In Vivo

2012 ◽  
pp. 321-358 ◽  
Author(s):  
Nicole J. Afacan ◽  
Laure M. Janot ◽  
Robert E. W. Hancock
Keyword(s):  
Antimicrobial Activity ◽  
Host Defense ◽  
Immune Modulation ◽  
Host Defense Peptides ◽  
Defense Peptides

scholarly journals Mechanistic Fingerprinting Reveals Kinetic Signatures of Resistance to Daptomycin and Host Defense Peptides in Streptococcus mitis-oralis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 404
Author(s):  
Michael R. Yeaman ◽  
Liana C. Chan ◽  
Nagendra N. Mishra ◽  
Arnold S. Bayer
Keyword(s):  
Flow Cytometry ◽  
Host Defense ◽  
Durable Resistance ◽  
Cross Resistance ◽  
Streptococcus Mitis ◽  
Host Defense Peptides ◽  
Strain Pair ◽  
Defense Peptides

Streptococcus mitis-oralis (S. mitis-oralis) infections are increasingly prevalent in specific populations, including neutropenic cancer and endocarditis patients. S. mitis-oralis strains have a propensity to evolve rapid, high-level and durable resistance to daptomycin (DAP-R) in vitro and in vivo, although the mechanism(s) involved remain incompletely defined. We examined mechanisms of DAP-R versus cross-resistance to cationic host defense peptides (HDPs), using an isogenic S. mitis-oralis strain-pair: (i) DAP-susceptible (DAP-S) parental 351-WT (DAP MIC = 0.5 µg/mL), and its (ii) DAP-R variant 351-D10 (DAP MIC > 256 µg/mL). DAP binding was quantified by flow cytometry, in-parallel with temporal (1–4 h) killing by either DAP or comparative prototypic cationic HDPs (hNP-1; LL-37). Multicolor flow cytometry was used to determine kinetic cell responses associated with resistance or susceptibility to these molecules. While overall DAP binding was similar between strains, a significant subpopulation of 351-D10 cells hyper-accumulated DAP (>2–4-fold vs. 351-WT). Further, both DAP and hNP-1 induced cell membrane (CM) hyper-polarization in 351-WT, corresponding to significantly greater temporal DAP-killing (vs. 351-D10). No strain-specific differences in CM permeabilization, lipid turnover or regulated cell death were observed post-exposure to DAP, hNP-1 or LL-37. Thus, the adaptive energetics of the CM appear coupled to the outcomes of interactions of S. mitis-oralis with DAP and selected HDPs. In contrast, altered CM permeabilization, proposed as a major mechanism of action of both DAP and HDPs, did not differentiate DAP-S vs. DAP-R phenotypes in this S. mitis-oralis strain-pair.

scholarly journals Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity

2018 ◽  
Vol 201 (3) ◽  
pp. 1007-1020 ◽  
Author(s):  
Suado M. Abdillahi ◽  
Tobias Maaß ◽  
Gopinath Kasetty ◽  
Adam A. Strömstedt ◽  
Maria Baumgarten ◽  
...  
Keyword(s):  
Host Defense ◽  
Collagen Vi ◽  
Host Defense Peptides ◽  
Defense Peptides

scholarly journals How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3

2019 ◽  
Vol 20 (21) ◽  
pp. 5289 ◽  
Author(s):  
Adenrele Oludiran ◽  
David S. Courson ◽  
Malia D. Stuart ◽  
Anwar R. Radwan ◽  
John C. Poutsma ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Host Defense ◽  
Bacterial Species ◽  
Membrane Curvature ◽  
Lessons Learned ◽  
Health Concern ◽  
Copper Binding ◽  
Bacterial Killing ◽  
Host Defense Peptides ◽  
Defense Peptides

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide–copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue.

Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity

Biochimie ◽  
2010 ◽  
Vol 92 (9) ◽  
pp. 1236-1241 ◽  
Author(s):  
Daisuke Takahashi ◽  
Sanjeev K. Shukla ◽  
Om Prakash ◽  
Guolong Zhang
Keyword(s):  
Antimicrobial Activity ◽  
Host Defense ◽  
Target Cell ◽  
Structural Determinants ◽  
Host Defense Peptides ◽  
Cell Selectivity ◽  
Defense Peptides

scholarly journals Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin

2011 ◽  
Vol 55 (6) ◽  
pp. 2880-2890 ◽  
Author(s):  
Gopinath Kasetty ◽  
Praveen Papareddy ◽  
Martina Kalle ◽  
Victoria Rydengård ◽  
Matthias Mörgelin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Host Defense ◽  
Host Defense Peptides ◽  
Content Type ◽  
Peptide Epitopes ◽  
Structure Activity ◽  
Human Thrombin ◽  
Defense Peptides ◽  
Anti Inflammatory

ABSTRACTPeptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteriaEscherichia coliandPseudomonas aeruginosa, the Gram-positive bacteriumStaphylococcus aureus, and the fungusCandida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock andP. aeruginosasepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

scholarly journals The Host Defense Peptide Beta-Defensin 1 Confers Protection against Bordetella pertussis in Newborn Piglets

2006 ◽  
Vol 74 (4) ◽  
pp. 2338-2352 ◽  
Author(s):  
Shokrollah Elahi ◽  
Rachelle M. Buchanan ◽  
Sam Attah-Poku ◽  
Hugh G. G. Townsend ◽  
Lorne A. Babiuk ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Host Defense ◽  
Bordetella Pertussis ◽  
Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Host Defense Peptides ◽  
Newborn Piglets ◽  
Defense Peptides

ABSTRACT Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 μg pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.

Human hemoglobin-derived peptides exhibit antimicrobial activity: a class of host defense peptides

2003 ◽  
Vol 791 (1-2) ◽  
pp. 345-356 ◽  
Author(s):  
Cornelia Liepke ◽  
Susann Baxmann ◽  
Cornelia Heine ◽  
Nicole Breithaupt ◽  
Ludger Ständker ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Host Defense ◽  
Human Hemoglobin ◽  
Host Defense Peptides ◽  
Defense Peptides

Antiviral Activities of Human Host Defense Peptides

2020 ◽  
Vol 27 (9) ◽  
pp. 1420-1443 ◽  
Author(s):  
David C. Brice ◽  
Gill Diamond
Keyword(s):  
Host Defense ◽  
Broad Spectrum ◽  
Structural Features ◽  
Host Defense Peptides ◽  
Enveloped Viruses ◽  
Human Host ◽  
Wide Range ◽  
Defense Peptides

Peptides with broad-spectrum antimicrobial activity are found widely expressed throughout nature. As they participate in a number of different aspects of innate immunity in mammals, they have been termed Host Defense Peptides (HDPs). Due to their common structural features, including an amphipathic structure and cationic charge, they have been widely shown to interact with and disrupt microbial membranes. Thus, it is not surprising that human HDPs have activity against enveloped viruses as well as bacteria and fungi. However, these peptides also exhibit activity against a wide range of non-enveloped viruses as well, acting at a number of different steps in viral infection. This review focuses on the activity of human host defense peptides, including alpha- and beta-defensins and the sole human cathelicidin, LL-37, against both enveloped and non-enveloped viruses. The broad spectrum of antiviral activity of these peptides, both in vitro and in vivo suggest that they play an important role in the innate antiviral defense against viral infections. Furthermore, the literature suggests that they may be developed into antiviral therapeutic agents.

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