Current and Potential Applications of Host-Defense Peptides and Proteins in Urology

The use of antibiotics has become increasingly disfavored as more multidrug resistant pathogens are on the rise. A promising alternative to the use of these conventional drugs includes antimicrobial peptides or host-defense peptides. These peptides typically consist of short amino acid chains with a net cationic charge and a substantial portion of hydrophobic residues. They mainly target the bacterial cell membrane but are also capable of translocating through the membrane and target intracellular components, making it difficult for bacteria to gain resistance as multiple essential cellular processes are being targeted. The use of these peptides in the field of biomedical therapies has been examined, and the different approaches to using them under various settings are constantly being discovered. In this review, we discuss the current and potential applications of these host-defense peptides in the field of urology. Besides the use of these peptides as antimicrobial agents, the value of these biological molecules has recently been expanded to their use as antitumor and anti-kidney-stone agents.

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Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action

International Journal of Molecular Sciences ◽

10.3390/ijms222011172 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11172

Author(s):

Matthew Drayton ◽

Julia P. Deisinger ◽

Kevin C. Ludwig ◽

Nigare Raheem ◽

Anna Müller ◽

...

Keyword(s):

Host Defense ◽

Bacterial Infections ◽

Multidrug Resistant ◽

Health Concern ◽

Rapid Rise ◽

Host Defense Peptides ◽

Viable Solution ◽

Defense Peptides ◽

Immunomodulatory Action ◽

Direct Killing

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed.

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Host Defense Peptides as Templates for Antifungal Drug Development

Journal of Fungi ◽

10.3390/jof6040241 ◽

2020 ◽

Vol 6 (4) ◽

pp. 241

Author(s):

Virginia Basso ◽

Dat Q. Tran ◽

André J. Ouellette ◽

Michael E. Selsted

Keyword(s):

Host Defense ◽

Fungal Pathogens ◽

Fungal Infections ◽

Multidrug Resistant ◽

Current Treatment ◽

Antifungal Drugs ◽

Antifungal Drug ◽

Host Defense Peptides ◽

Invasive Fungal Diseases ◽

Defense Peptides

Current treatment for invasive fungal diseases is limited to three classes of antifungal drugs: azoles, polyenes, and echinocandins. The most recently introduced antifungal class, the echinocandins, was first approved nearly 30 years ago. The limited antifungal drug portfolio is rapidly losing its clinical utility due to the inexorable rise in the incidence of invasive fungal infections and the emergence of multidrug resistant (MDR) fungal pathogens. New antifungal therapeutic agents and novel approaches are desperately needed. Here, we detail attempts to exploit the antifungal and immunoregulatory properties of host defense peptides (HDPs) in the design and evaluation of new antifungal therapeutics and discuss historical limitations and recent advances in this quest.

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Peptide Antimicrobial Agents

Clinical Microbiology Reviews ◽

10.1128/cmr.00056-05 ◽

2006 ◽

Vol 19 (3) ◽

pp. 491-511 ◽

Cited By ~ 1429

Author(s):

Håvard Jenssen ◽

Pamela Hamill ◽

Robert E. W. Hancock

Keyword(s):

Host Defense ◽

Antimicrobial Agents ◽

Antibacterial Activities ◽

Antimicrobial Activities ◽

Host Defense Peptides ◽

Important Host ◽

Defense Peptides ◽

And Function ◽

The Relationship ◽

Defense Molecules

SUMMARY Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.

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Geographically Distinct Expression Profile of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae

Asian Herpetological Research ◽

10.3724/sp.j.1245.2013.00288 ◽

2014 ◽

Vol 4 (4) ◽

pp. 288-297

Author(s):

LING Guiying ◽

LI Li ◽

GAO Jiuxiang ◽

YU Haining ◽

WANG Yipeng ◽

...

Keyword(s):

Host Defense ◽

Expression Profile ◽

Host Defense Peptides ◽

Defense Peptides

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Human Host Defense Peptides - Role in Maintaining Human Homeostasis and Pathological Processes

Current Medicinal Chemistry ◽

10.2174/0929867323666161213100443 ◽

2017 ◽

Vol 24 (7) ◽

pp. 654-672 ◽

Cited By ~ 2

Author(s):

Malgorzata Anna Dawgul ◽

Katarzyna E. Greber ◽

Wieslaw Sawicki ◽

Wojciech Kamysz

Keyword(s):

Host Defense ◽

Host Defense Peptides ◽

Human Host ◽

Defense Peptides

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

Antibiotics ◽

10.3390/antibiotics10040404 ◽

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.

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