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

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.

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Host Defense Peptides: Immune Modulation and Antimicrobial Activity In Vivo

Antimicrobial Peptides and Innate Immunity ◽

10.1007/978-3-0348-0541-4_13 ◽

2012 ◽

pp. 321-358 ◽

Cited By ~ 3

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

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

Infection and Immunity ◽

10.1128/iai.74.4.2338-2352.2006 ◽

2006 ◽

Vol 74 (4) ◽

pp. 2338-2352 ◽

Cited By ~ 49

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.

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Antiviral Activities of Human Host Defense Peptides

Current Medicinal Chemistry ◽

10.2174/0929867326666190805151654 ◽

2020 ◽

Vol 27 (9) ◽

pp. 1420-1443 ◽

Cited By ~ 16

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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In vitro and in vivo evaluation of implantable bacterial-killing coatings based on host defense peptides and their synthetic mimics

Journal of Material Science and Technology ◽

10.1016/j.jmst.2021.02.047 ◽

2021 ◽

Author(s):

Yuxin Qian ◽

Shuai Deng ◽

Xue Wu ◽

Yunrui She ◽

Runhui Liu ◽

...

Keyword(s):

Host Defense ◽

In Vivo Evaluation ◽

Bacterial Killing ◽

Host Defense Peptides ◽

Defense Peptides

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Host defense peptides for treatment of colorectal carcinoma - a comparative in vitro and in vivo analysis

Oncotarget ◽

10.18632/oncotarget.2039 ◽

2014 ◽

Vol 5 (12) ◽

pp. 4467-4479 ◽

Cited By ~ 13

Author(s):

Claudia Maletzki ◽

Ulrike Klier ◽

Samuel Marinkovic ◽

Ernst Klar ◽

Jörg Andrä ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Host Defense ◽

Host Defense Peptides ◽

In Vivo Analysis ◽

Defense Peptides

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Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity

Scientific Reports ◽

10.1038/s41598-021-97779-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tünde Juhász ◽

Mayra Quemé-Peña ◽

Bence Kővágó ◽

Judith Mihály ◽

Maria Ricci ◽

...

Keyword(s):

Lipid Bilayers ◽

Host Defense ◽

Great Promise ◽

Microbial Infection ◽

Host Defense Peptides ◽

Membrane Activity ◽

Defense Peptides ◽

Bacterial Lipid

AbstractIn the emerging era of antimicrobial resistance, the susceptibility to co-infections of patients suffering from either acquired or inherited hemolytic disorders can lead to dramatic increase in mortality rates. Closely related, heme liberated during hemolysis is one of the major sources of iron, which is vital for both host and invading microorganisms. While recent intensive research in the field has demonstrated that heme exerts diverse local effects including impairment of immune cells functions, it is almost completely unknown how it may compromise key molecules of our innate immune system, such as antimicrobial host defense peptides (HDPs). Since HDPs hold great promise as natural therapeutic agents against antibiotic-resistant microbes, understanding the effects that may modulate their action in microbial infection is crucial. Here we explore how hemin can interact directly with selected HDPs and influence their structure and membrane activity. It is revealed that induced helical folding, large assembly formation, and altered membrane activity is promoted by hemin. However, these effects showed variations depending mainly on peptide selectivity toward charged lipids, and the affinity of the peptide and hemin to lipid bilayers. Hemin-peptide complexes are sought to form semi-folded co-assemblies, which are present even with model membranes resembling mammalian or bacterial lipid compositions. In vitro cell-based toxicity assays supported that toxic effects of HDPs could be attenuated due to their assembly formation. These results are in line with our previous findings on peptide-lipid-small molecule systems suggesting that small molecules present in the complex in vivo milieu can regulate HDP function. Inversely, diverse effects of endogenous compounds could also be manipulated by HDPs.

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