Host Defense Peptide-Mimicking Polymers and Polymeric-Brush-Tethered Host Defense Peptides: Recent Developments, Limitations, and Potential Success

Amphiphilic antimicrobial polymers have attracted considerable interest as structural mimics of host defense peptides (HDPs) that provide a broad spectrum of activity and do not induce bacterial-drug resistance. Likewise, surface engineered polymeric-brush-tethered HDP is considered a promising coating strategy that prevents infections and endows implantable materials and medical devices with antifouling and antibacterial properties. While each strategy takes a different approach, both aim to circumvent limitations of HDPs, enhance physicochemical properties, therapeutic performance, and enable solutions to unmet therapeutic needs. In this review, we discuss the recent advances in each approach, spotlight the fundamental principles, describe current developments with examples, discuss benefits and limitations, and highlight potential success. The review intends to summarize our knowledge in this research area and stimulate further work on antimicrobial polymers and functionalized polymeric biomaterials as strategies to fight infectious diseases.

Download Full-text

Antimicrobial Polymers: Molecular Design as Synthetic Mimics of Host-Defense Peptides

ACS Symposium Series - Tailored Polymer Architectures for Pharmaceutical and Biomedical Applications ◽

10.1021/bk-2013-1135.ch019 ◽

2013 ◽

pp. 319-330 ◽

Cited By ~ 10

Author(s):

Edmund F. Palermo ◽

Satyavani Vemparala ◽

Kenichi Kuroda

Keyword(s):

Host Defense ◽

Molecular Design ◽

Host Defense Peptides ◽

Antimicrobial Polymers ◽

Defense Peptides

Download Full-text

Interaction of the core fragments of the LL-37 host defense peptide with actin

RSC Advances ◽

10.1039/c4ra13007c ◽

2015 ◽

Vol 5 (13) ◽

pp. 9361-9367 ◽

Cited By ~ 5

Author(s):

Asaf Sol ◽

Guangshun Wang ◽

Edna Blotnick ◽

Radha Golla ◽

Gilad Bachrach ◽

...

Keyword(s):

Innate Immunity ◽

Host Defense ◽

Host Defense Peptides ◽

Effector Molecules ◽

The Core ◽

Health Promoting ◽

Host Defense Peptide ◽

Defense Peptides

Host defense peptides are effector molecules of the innate immunity that possess antimicrobial and health-promoting properties.

Download Full-text

Host Defense Peptide Resistance Contributes to Colonization and Maximal Intestinal Pathology by Crohn's Disease-Associated Adherent-Invasive Escherichia coli

Infection and Immunity ◽

10.1128/iai.01888-14 ◽

2014 ◽

Vol 82 (8) ◽

pp. 3383-3393 ◽

Cited By ~ 25

Author(s):

Joseph B. McPhee ◽

Cherrie L. Small ◽

Sarah A. Reid-Yu ◽

John R. Brannon ◽

Hervé Le Moual ◽

...

Keyword(s):

Escherichia Coli ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Host Defense ◽

Bacterial Killing ◽

Host Defense Peptides ◽

Content Type ◽

Host Defense Peptide ◽

Defense Peptides ◽

High Level

ABSTRACTHost defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associatedEscherichia colicommonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasiveE. coli(AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6,arlA, which encodes a Mig-14 family protein implicated in defensin resistance, andarlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut.

Download Full-text

Antimicrobial polymers as synthetic mimics of host-defense peptides

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology ◽

10.1002/wnan.1199 ◽

2012 ◽

Vol 5 (1) ◽

pp. 49-66 ◽

Cited By ~ 93

Author(s):

Kenichi Kuroda ◽

Gregory A. Caputo

Keyword(s):

Host Defense ◽

Host Defense Peptides ◽

Antimicrobial Polymers ◽

Defense Peptides

Download Full-text

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

Download Full-text

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

Download Full-text

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.

Download Full-text