scholarly journals Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action

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.

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.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Joey Chor Yee Lo ◽  
Dirk Lange
Keyword(s):  
Host Defense ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Biological Molecules ◽  
Host Defense Peptides ◽  
Promising Alternative ◽  
Cellular Processes ◽  
Potential Applications ◽  
Defense Peptides ◽  
Bacterial Cell Membrane

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.

scholarly journals Host Defense Peptides as Templates for Antifungal Drug Development

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.

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

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

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

2017 ◽  
Vol 24 (7) ◽  
pp. 654-672 ◽  
Author(s):  
Malgorzata Anna Dawgul ◽  
Katarzyna E. Greber ◽  
Wieslaw Sawicki ◽  
Wojciech Kamysz
Keyword(s):  
Host Defense ◽  
Host Defense Peptides ◽  
Human Host ◽  
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 Genomic Characterization of New Variant of Hydrogen Sulfide (H2S)-Producing Escherichia coli with Multidrug Resistance Properties Carrying the mcr-1 Gene in China

Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 80 ◽  
Author(s):  
Silpak Biswas ◽  
Mohammed Elbediwi ◽  
Guimin Gu ◽  
Min Yue
Keyword(s):  
Escherichia Coli ◽  
Hydrogen Sulfide ◽  
Multidrug Resistance ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Colistin Resistance ◽  
New Variant ◽  
Genomic Characterization ◽  
Human Infections

Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a hydrogen sulfide (H2S)-producing Escherichia coli variant isolated from a human in China, with multidrug resistance (MDR) properties, including colistin resistance by the mcr-1 gene, which could have great implications for the treatment of human infections.

scholarly journals Nano-mechanical in-process monitoring of antimicrobial poration in model phospholipid bilayers

RSC Advances ◽  
2017 ◽  
Vol 7 (31) ◽  
pp. 19081-19084
Author(s):  
Andrea Valsesia ◽  
Patrizia Iavicoli ◽  
Helen Lewis ◽  
Cloé Desmet ◽  
Dora Mehn ◽  
...  
Keyword(s):  
Process Monitoring ◽  
Host Defense ◽  
Phospholipid Bilayers ◽  
Host Defense Peptides ◽  
Defense Peptides ◽  
Membrane Poration

Nanomechanical monitoring of known mechanisms of membrane poration mediated by host defense peptides is reported.

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