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Article ; Online: Assessing biofilm inhibition and immunomodulatory activity of small amounts of synthetic host defense peptides synthesized using SPOT-array technology.

Etayash, Hashem / Haney, Evan F / Hancock, Robert E W

2021 Volume 16, Issue 4, Page(s) 1850–1870

Abstract: Peptides are promising drug candidates because of their diversity, biocompatibility and spectrum of activities. Here, we describe a protocol for high-throughput screening of SPOT-peptide arrays to assess the antibiofilm, antimicrobial and ... ...

Abstract	Peptides are promising drug candidates because of their diversity, biocompatibility and spectrum of activities. Here, we describe a protocol for high-throughput screening of SPOT-peptide arrays to assess the antibiofilm, antimicrobial and immunomodulatory activities of synthetic peptides. It is a Protocol Extension of our previous Nature Protocols article, which describes the synthesis of SPOT-peptide arrays and assays for screening antimicrobial activity. This latest protocol allows the simultaneous assessment of hundreds of synthetic host defense peptides to define their overall activity profiles and identify candidate sequences that are suitable for further characterization and development as anti-infectives. When coupled with the SPOT-array technology for peptide synthesis, the described procedures are rapid, inexpensive and straightforward for peptide library screening. The protocols can be implemented in most microbiology or immunology research laboratories without the need for specialists. The time to complete each step ranges between 1 and 4 h with overnight pauses, and datasets related to the antibiofilm and immunomodulatory activities of a large set of peptide sequences can be generated in a few days.
MeSH term(s)	Antimicrobial Cationic Peptides/chemical synthesis ; Antimicrobial Cationic Peptides/pharmacology ; Biofilms/drug effects ; Cell Death/drug effects ; Humans ; Immunologic Factors/pharmacology ; Protein Array Analysis/methods
Chemical Substances	Antimicrobial Cationic Peptides ; Immunologic Factors
Language	English
Publishing date	2021-04-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2244966-8
ISSN	1750-2799 ; 1754-2189
ISSN (online)	1750-2799
ISSN	1754-2189
DOI	10.1038/s41596-021-00500-w
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Article: Antibiofilm peptides enhance the corrosion resistance of titanium in the presence of

Wang, Dan / Yue, Yingying / Liu, He / Zhang, Tian / Haney, Evan F / Hancock, Robert E W / Yu, Jian / Shen, Ya

Frontiers in bioengineering and biotechnology

2024 Volume 11, Page(s) 1339912

Abstract: Titanium alloys have gained popularity in implant dentistry for the restoration of missing teeth and related hard tissues because of their biocompatibility and enhanced strength. However, titanium corrosion and infection caused by microbial biofilms ... ...

Abstract	Titanium alloys have gained popularity in implant dentistry for the restoration of missing teeth and related hard tissues because of their biocompatibility and enhanced strength. However, titanium corrosion and infection caused by microbial biofilms remains a significant clinical challenge leading to implant failure. This study aimed to evaluate the effectiveness of antibiofilm peptides 1018 and DJK-5 on the corrosion resistance of titanium in the presence of
Language	English
Publishing date	2024-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2023.1339912
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Article ; Online: Microtiter plate assays to assess antibiofilm activity against bacteria.

Haney, Evan F / Trimble, Michael J / Hancock, Robert E W

Nature protocols

2021 Volume 16, Issue 5, Page(s) 2615–2632

Abstract: Bacterial biofilms demonstrate high broad-spectrum adaptive antibiotic resistance and cause two thirds of all infections, but there is a lack of approved antibiofilm agents. Unlike the standard minimal inhibitory concentration assay to assess ... ...

Abstract	Bacterial biofilms demonstrate high broad-spectrum adaptive antibiotic resistance and cause two thirds of all infections, but there is a lack of approved antibiofilm agents. Unlike the standard minimal inhibitory concentration assay to assess antibacterial activity against planktonic cells, there is no standardized method to evaluate biofilm inhibition and/or eradication capacity of novel antibiofilm compounds. The protocol described here outlines simple and reproducible methods for assessing the biofilm inhibition and eradication capacities of novel antibiofilm agents against adherent bacterial biofilms grown in 96-well microtiter plates. It employs two inexpensive dyes: crystal violet to stain adhered biofilm biomass and 2,3,5-triphenyl tetrazolium chloride to quantify metabolism of the biofilm cells. The procedure is accessible to any laboratory with a plate reader, requires minimal technical expertise or training and takes 4 or 5 d to complete. Recommendations for how biofilm inhibition and eradication results should be interpreted and presented are also described.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Bacterial Adhesion/drug effects ; Bacterial Physiological Phenomena/drug effects ; Biofilms/drug effects ; Biofilms/growth & development ; Biological Assay/methods ; Microtechnology/methods ; Time Factors
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2244966-8
ISSN	1750-2799 ; 1754-2189
ISSN (online)	1750-2799
ISSN	1754-2189
DOI	10.1038/s41596-021-00515-3
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Article ; Online: Antibiofilm activity of host defence peptides: complexity provides opportunities.

Hancock, Robert E W / Alford, Morgan A / Haney, Evan F

Nature reviews. Microbiology

2021 Volume 19, Issue 12, Page(s) 786–797

Abstract: Host defence peptides (HDPs) are integral components of innate immunity across all living organisms. These peptides can exert direct antibacterial effects, targeting planktonic cells (referred to as antimicrobial peptides), and exhibit antibiofilm ( ... ...

Abstract	Host defence peptides (HDPs) are integral components of innate immunity across all living organisms. These peptides can exert direct antibacterial effects, targeting planktonic cells (referred to as antimicrobial peptides), and exhibit antibiofilm (referred to as antibiofilm peptides), antiviral, antifungal and host-directed immunomodulatory activities. In this Review, we discuss how the complex functional attributes of HDPs provide many opportunities for the development of antimicrobial therapeutics, focusing particularly on their emerging antibiofilm properties. The mechanisms of action of antibiofilm peptides are compared and contrasted with those of antimicrobial peptides. Furthermore, obstacles for the practical translation of candidate peptides into therapeutics and the potential solutions are discussed. Critically, HDPs have the value-added assets of complex functional attributes, particularly antibiofilm and anti-inflammatory activities and their synergy with conventional antibiotics.
MeSH term(s)	Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Antifungal Agents/chemistry ; Antifungal Agents/pharmacology ; Antimicrobial Cationic Peptides/chemistry ; Antimicrobial Cationic Peptides/pharmacology ; Antimicrobial Peptides/chemistry ; Antimicrobial Peptides/pharmacology ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Biofilms/drug effects ; Immunity, Innate ; Immunomodulating Agents/chemistry ; Immunomodulating Agents/pharmacology
Chemical Substances	Anti-Bacterial Agents ; Anti-Infective Agents ; Anti-Inflammatory Agents ; Antifungal Agents ; Antimicrobial Cationic Peptides ; Antimicrobial Peptides ; Antiviral Agents ; Immunomodulating Agents
Language	English
Publishing date	2021-06-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/s41579-021-00585-w
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Zs.A 5865: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Dynamic killing effectiveness of mouthrinses and a d-enantiomeric peptide on oral multispecies biofilms grown on dental restorative material surfaces.

Hu, Jinghao / Yu, Jian / Liu, He / Wang, Zhejun / Haapasalo, Markus / Haney, Evan F / Hancock, Robert E W / Deng, Shuli / Shen, Ya

Journal of dentistry

2023 Volume 134, Page(s) 104552

Abstract: Objective: To evaluate the dynamics of killing of oral multispecies biofilms grown on dental restorative materials by commercially available mouthrinses and a d-enantiomeric peptide.: Methods: Four composite resins (3 M Supreme, 3 M Supreme flow, ... ...

Abstract	Objective: To evaluate the dynamics of killing of oral multispecies biofilms grown on dental restorative materials by commercially available mouthrinses and a d-enantiomeric peptide. Methods: Four composite resins (3 M Supreme, 3 M Supreme flow, Kerr Sonicfill, and Shofu Beautifil II) and one glass ionomer (GC Fuji II) were used as restorative materials. Plaque biofilms were grown on the surfaces of restorative material discs for 1 week. The surface roughness and biofilm attachment were assessed by atomic force microscopy and scanning electron microscopy. One-week-old biofilms grown anaerobically at 37 °C were exposed to each of five solutions for one minute (twice daily for seven days): Listerine Total care and Paroex Gum mouthrinses, 0.12% chlorhexidine, 0.001% d-enantiomeric peptide DJK-5, and sterile water. The dynamic variation of the biovolume of the biofilms and the percentage of dead bacteria were monitored and analyzed using confocal laser scanning microscopy. Results: All restorative materials had similar surface roughness with intact biofilm attachment. The percentage of dead bacteria and biovolume of biofilms treated by each oral rinse solution remained constant between days 1 and 7, with no statistically significant difference. DJK-5 showed the highest percentage of dead bacteria (up to 75.7%; cf. ∼20-40% for other mouthrinses) of all solutions tested within 7 days. Conclusions: DJK-5 outperformed conventional mouthrinses in killing bacteria in oral multispecies biofilms grown on dental restorative materials. Clinical significance: The antimicrobial peptide DJK-5 is effective against oral biofilms and serves as a promising candidate for the development of future mouthrinses to improve long-term oral hygiene.
MeSH term(s)	Humans ; Chlorhexidine/pharmacology ; Peptides ; Mouthwashes/pharmacology ; Dental Plaque ; Bacteria ; Biofilms
Chemical Substances	Chlorhexidine (R4KO0DY52L) ; Peptides ; Mouthwashes
Language	English
Publishing date	2023-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186068-9
ISSN	1879-176X ; 0300-5712
ISSN (online)	1879-176X
ISSN	0300-5712
DOI	10.1016/j.jdent.2023.104552
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Zs.A 860: Show issues

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Article ; Online: Influence of a D-enantiomeric peptide on the anticorrosion ability of titanium with different surface roughness against Streptococcus mutans biofilms.

Wang, Dan / Yu, Jian / Liu, He / Zhang, Tian / Haney, Evan F / Hancock, Robert E W / Peng, Lin / Shen, Ya

Journal of dentistry

2023 Volume 139, Page(s) 104777

Abstract: Objective: To investigate the effectiveness of a d-enantiomeric antibiofilm peptide (DJK-5) on the anticorrosion ability of titanium (Ti) with different surface roughness against Streptococcus mutans biofilms.: Methods: Commercially pure Ti disks ... ...

Abstract	Objective: To investigate the effectiveness of a d-enantiomeric antibiofilm peptide (DJK-5) on the anticorrosion ability of titanium (Ti) with different surface roughness against Streptococcus mutans biofilms. Methods: Commercially pure Ti disks with machined (MA, smooth) or sandblasted + acid-etched (SLA, rough) surfaces were prepared and characterized. All disks were divided into three groups: a positive control (PC) group with S. mutans, a DJK-5-treated group, and a negative control (NC) group without S. mutans. Biofilm formation and corrosion on Ti surfaces were determined by confocal laser scanning microscopy and scanning electron microscopy after 2 and 6 days, and the electrochemical properties were evaluated. Results: Ten μg/mL of DJK-5 killed 83.3 % and 87.4 % of biofilms on SLA and MA Ti surfaces, respectively after 2 days, and 72.9 % and 77.7 % after 6 days, with more bacteria surviving on SLA surfaces with higher roughness (p < 0.05). DJK-5 treatment induced less surface defects with tiny pit corrosion than PC. DJK-5 treatment when compared to PC, led to electrochemical properties more reflecting NC surfaces, including significantly less negative corrosion potential, lower corrosion current, and higher passive film resistance (p < 0.05). SLA surfaces exhibited higher current density and lower resistance than MA surfaces (p < 0.05). Conclusion: DJK-5 effectively enhanced the corrosion resistance of Ti with different surface roughness while killing S. mutans biofilms, and smooth surfaces were more susceptible to peptide treatment. Clinical significance: The antibiofilm peptide is promising for promoting the anticorrosion ability of Ti against biofilms, thereby preventing biofilm-related infections.
MeSH term(s)	Titanium/pharmacology ; Titanium/chemistry ; Streptococcus mutans ; Biofilms ; Peptides ; Microscopy, Electron, Scanning ; Surface Properties
Chemical Substances	Titanium (D1JT611TNE) ; Peptides
Language	English
Publishing date	2023-11-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186068-9
ISSN	1879-176X ; 0300-5712
ISSN (online)	1879-176X
ISSN	0300-5712
DOI	10.1016/j.jdent.2023.104777
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Article: Reassessing the Host Defense Peptide Landscape.

Haney, Evan F / Straus, Suzana K / Hancock, Robert E W

Frontiers in chemistry

2019 Volume 7, Page(s) 43

Abstract: Current research has demonstrated that small cationic amphipathic peptides have strong potential not only as antimicrobials, but also as antibiofilm agents, immune modulators, and anti-inflammatories. Although traditionally termed antimicrobial peptides ( ...

Abstract	Current research has demonstrated that small cationic amphipathic peptides have strong potential not only as antimicrobials, but also as antibiofilm agents, immune modulators, and anti-inflammatories. Although traditionally termed antimicrobial peptides (AMPs) these additional roles have prompted a shift in terminology to use the broader term host defense peptides (HDPs) to capture the multi-functional nature of these molecules. In this review, we critically examined the role of AMPs and HDPs in infectious diseases and inflammation. It is generally accepted that HDPs are multi-faceted mediators of a wide range of biological processes, with individual activities dependent on their polypeptide sequence. In this context, we explore the concept of chemical space as it applies to HDPs and hypothesize that the various functions and activities of this class of molecule exist on independent but overlapping activity landscapes. Finally, we outline several emerging functions and roles of HDPs and highlight how an improved understanding of these processes can potentially be leveraged to more fully realize the therapeutic promise of HDPs.
Language	English
Publishing date	2019-02-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2019.00043
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Article ; Online: Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002.

Esposito, Tullio V F / Blackadar, Colin / Wu, Lan / Rodríguez-Rodríguez, Cristina / Haney, Evan F / Pletzer, Daniel / Saatchi, Katayoun / Hancock, Robert E W / Häfeli, Urs O

Molecular pharmaceutics

2024

Abstract: Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with promising immunomodulatory and antibiofilm properties. An appreciable body of work exists around its mechanism of action at the cellular and molecular level, along with its efficacy ... ...

Abstract	Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with promising immunomodulatory and antibiofilm properties. An appreciable body of work exists around its mechanism of action at the cellular and molecular level, along with its efficacy across several infection and inflammation models. However, little is known about its absorption, distribution, and excretion in live organisms. Here, we performed a comprehensive biodistribution assessment with a gallium-67 radiolabeled derivative of IDR-1002 using nuclear tracing techniques. Various dose levels of the radiotracer (2-40 mg/kg) were administered into the blood, peritoneal cavity, and subcutaneous tissue, or instilled into the lungs. The peptide was well tolerated at all subcutaneous and intraperitoneal doses, although higher levels were associated with delayed absorption kinetics and precipitation of the peptide within the tissues. Low intratracheal doses were rapidly absorbed systemically, and small increases in the dose level were lethal. Intravenous doses were rapidly cleared from the blood at lower levels, and upon escalation, were toxic with a high proportion of the dose accumulating within the lung tissue. To improve biocompatibility and prolong its circulation within the blood, IDR-1002 was further formulated onto high molecular weight hyperbranched polyglycerol (HPG) polymers. Constructs prepared at 5:1 and 10:1 peptide-to-polymer ratios were colloidally stable, maintained the biological profile of the peptide payload and helped reduce red blood cell lysis. The 5:1 construct circulated well in the blood, but higher peptide loading was associated with rapid clearance by the reticuloendothelial system. Many peptides face pharmacokinetic and biocompatibility challenges, but formulations such as those with HPG have the potential to overcome these limitations.
Language	English
Publishing date	2024-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.3c01169
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Article ; Online: Identification of a crocodylian β-defensin variant from Alligator mississippiensis with antimicrobial and antibiofilm activity.

Santana, Felix L / Arenas, Iván / Haney, Evan F / Estrada, Karel / Hancock, Robert E W / Corzo, Gerardo

Peptides

2021 Volume 141, Page(s) 170549

Abstract: β-defensin host defense peptides are important components of the innate immune system of vertebrates. Although evidence of their broad antimicrobial, antibiofilm and immunomodulatory activities in mammals have been presented, β-defensins from other ... ...

Abstract	β-defensin host defense peptides are important components of the innate immune system of vertebrates. Although evidence of their broad antimicrobial, antibiofilm and immunomodulatory activities in mammals have been presented, β-defensins from other vertebrate species, like crocodylians, remain largely unexplored. In this study, five new crocodylian β-defensin variants from Alligator mississippiensis and Crocodylus porosus were selected for synthesis and characterization based on their charge and hydrophobicity values. Linear peptides were synthesized, folded, purified and then evaluated for their antimicrobial and antibiofilm activities against the bacterial pathogens, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, Enterobacter cloacae and Acinetobacter baumannii. The Am23SK variant (SCRFSGGYCIWNWERCRSGHFLVALCPFRKRCCK) from A. mississippiensis displayed promising activity against both planktonic cells and bacterial biofilms, outperforming the human β-defensin 3 under the experimental conditions. Moreover, Am23SK exhibited no cytotoxicity towards mammalian cells and exerted immunomodulatory effects in vitro, moderately suppressing the production of proinflammatory mediators from stimulated human bronchial epithelial cells. Overall, our results have expanded the activity landscape of crocodylian and reptilian β-defensin in general.
MeSH term(s)	Alligators and Crocodiles ; Animals ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Biofilms/drug effects ; Cell Line ; Epithelial Cells ; Humans ; Immunomodulating Agents/chemistry ; Immunomodulating Agents/pharmacology ; Microbial Sensitivity Tests ; Protein Folding ; beta-Defensins/chemical synthesis ; beta-Defensins/chemistry ; beta-Defensins/pharmacology
Chemical Substances	Anti-Bacterial Agents ; DEFB103A protein, human ; Immunomodulating Agents ; beta-Defensins
Language	English
Publishing date	2021-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2021.170549
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Zs.A 1649: Show issues

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Article ; Online: Host Response of Human Epidermis to Methicillin-Resistant

Wu, Bing Catherine / Blimkie, Travis M / Haney, Evan F / Falsafi, Reza / Akhoundsadegh, Noushin / Hancock, Robert E W

Cells

2022 Volume 11, Issue 21

Abstract: Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant, and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model ... ...

Abstract	Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant, and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of thermally-injured epidermis to methicillin-resistant
MeSH term(s)	Humans ; Methicillin-Resistant Staphylococcus aureus/physiology ; Anti-Bacterial Agents/pharmacology ; Biofilms ; Epidermis/metabolism ; Peptides/metabolism ; Inflammation/metabolism
Chemical Substances	Anti-Bacterial Agents ; Peptides
Language	English
Publishing date	2022-11-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11213459
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