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Antimicrobial peptides

Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Berkay Ozcelik, Renxun Chen, Veronica Glattauer, Naresh Kumar, MarkD P Willcox, Helmut Thissen
Control over biointerfacial interactions on material surfaces is of significant interest in many biomedical applications and extends from the modulation of protein adsorption and cellular responses to the inhibition of bacterial attachment and biofilm formation. Effective control over biointerfaces is best achieved by reducing nonspecific interactions on the surface while also displaying specific bioactive signals. A poly(ethylene glycol) (PEG)-based multifunctional coating has been developed that provides effective reduction of protein fouling while enabling covalent immobilization of peptides in a one or two-step manner...
October 20, 2016: Macromolecular Bioscience
Sonia Fieulaine, Rodolphe Alves de Sousa, Laure Maigre, Karim Hamiche, Mickael Alimi, Jean-Michel Bolla, Abbass Taleb, Alexis Denis, Jean-Marie Pagès, Isabelle Artaud, Thierry Meinnel, Carmela Giglione
Peptide deformylase (PDF) is considered an excellent target to develop antibiotics. We have performed an extensive characterization of a new PDF from the pathogen Streptococcus agalactiae, showing properties similar to other known PDFs. S. agalactiae PDF could be used as PDF prototype as it allowed to get complete sets of 3-dimensional, biophysical and kinetic data with virtually any inhibitor compound. Structure-activity relationship analysis with this single reference system allowed us to reveal distinct binding modes for different PDF inhibitors and the key role of a hydrogen bond in potentiating the interaction between ligand and target...
October 20, 2016: Scientific Reports
Oleg M Michurin, Sergii Afonin, Marina Berditsch, Constantin G Daniliuc, Anne S Ulrich, Igor V Komarov, Dmytro S Radchenko
Conformationally constrained non-racemizing trifluoromethyl-substituted lysine isosteres [(E)- and (Z)-TCBLys] with charged side chains are presented as a new type of (19) F-NMR labels for peptide studies. Design of the labels, their synthesis, incorporation into peptides and experimental demonstration of their application for solid state NMR studies of membrane-active peptides are described. A series of fluorine-labeled analogues of the helical amphipathic antimicrobial peptide PGLa(Nle) was obtained, in which different lysine residues in the original peptide sequence were replaced, one at a time, by either (E)- or (Z)-TCBLys...
October 20, 2016: Angewandte Chemie
Sanae Sekihara, Toshio Shibata, Mai Hyakkendani, Shun-Ichiro Kawabata
We recently reported that transglutaminase (TG) suppresses immune deficiency pathway-controlled antimicrobial peptides (IMD-AMPs), thereby conferring immune tolerance to gut microbes, and that RNAi of the TG gene in flies decreases the lifespan compared with non-TG-RNAi flies. Here, analysis of the bacterial composition of the Drosophila gut by next-generation sequencing revealed that gut microbiota comprising one dominant genus of Acetobacter in non-TG-RNAi flies was shifted to that comprising two dominant genera of Acetobacter and Providencia in TG-RNAi flies...
October 19, 2016: Journal of Biological Chemistry
Yutaka Sugi, Kyoko Takahashi, Kenta Kurihara, Kou Nakano, Tetsuro Kobayakawa, Kazuaki Nakata, Masato Tsuda, Shigemasa Hanazawa, Akira Hosono, Shuichi Kaminogawa
α-Defensin 5 is important to both maintenance of a gut microbiota and host immunity. While previous reports have shown that gut bacteria are able to upregulate α-defensin 5 through Toll-like receptor signaling, we demonstrate here that α-defensin 5 expression can also be regulated by microbial metabolites. Among these, lactate appeared to significantly suppress α-defensin 5 gene transcription. Actually, fractions of <3 kD compounds obtained from the ceca of SPF mice were suppressed α-defensin 5 gene transcription at specific concentrations...
October 20, 2016: Bioscience, Biotechnology, and Biochemistry
Francis D O Ablan, B Logan Spaller, Kaitlyn I Abdo, Paulo F Almeida
Hundreds of cationic antimicrobial and cell-penetrating peptides (CPPs) form amphipathic α-helices when bound to lipid membranes. Here, we test two hypotheses for the differences in the ability of these peptides to translocate across membranes. The first, which we now call the hydrophobicity hypothesis, is that peptide translocation is determined by the Gibbs energy of insertion into the bilayer from the membrane interface. The second, which we call the charge-distribution hypothesis, is that translocation is determined by whether the distribution of cationic residues in the peptide can transiently stabilize a high-energy inserted intermediate by forming salt bridges to the phosphates of lipid headgroups...
October 18, 2016: Biophysical Journal
Aritreyee Datta, Vikas Yadav, Anirban Ghosh, Jaesun Choi, Dipita Bhattacharyya, Rajiv K Kar, Humaira Ilyas, Arkajyoti Dutta, Eunseol An, Jayanta Mukhopadhyay, Dongkuk Lee, Kaustuv Sanyal, Ayyalusamy Ramamoorthy, Anirban Bhunia
There is a significant need for developing compounds that kill Cryptococcus neoformans, the fungal pathogen that causes meningoencephalitis in immunocompromised individuals. Here, we report the mode of action of a designed antifungal peptide, VG16KRKP (VARGWKRKCPLFGKGG) against C. neoformans. It is shown that VG16KRKP kills fungal cells mainly through membrane compromise leading to efflux of ions and cell metabolites. Intracellular localization, inhibition of in vitro transcription, and DNA binding suggest a secondary mode of action for the peptide, hinting at possible intracellular targets...
October 18, 2016: Biophysical Journal
Jelmer Sjollema, Heidrun Keul, Henny van der Mei, René Dijkstra, Minie Rustema-Abbing, Joop de Vries, Ton Loontjens, Ton Dirks, Henk Busscher
Various potential anti-infection strategies can be thought of for biomaterial implants and devices. Permanent, tissue-integrated implants such as artificial joint prostheses require a different anti-infection strategy than, for instance, removable urinary catheters. The different requirements set to biomaterials implants and devices in different clinical applications call for tailor-made strategies. Here, a modular coating-concept for biomaterials is reported, which in its full, trifunctional form comprises nonadhesiveness to bacteria and antimicrobial release, combined with enhanced tissue integration characteristics...
October 19, 2016: Macromolecular Bioscience
Jlenia Brunetti, Giulia Roscia, Ilaria Lampronti, Roberto Gambari, Leila Quercini, Chiara Falciani, Luisa Bracci, Alessandro Pini
The synthetic antimicrobial peptide SET-M33 has strong activity against bacterial infections due to Gram-negative bacteria. It is currently in preclinical development as a new drug to treat lung infections caused by Gram-negative bacteria. Here we report its strong anti-inflammatory activity in terms of reduced expression of a number of cytokines, enzymes and signal transduction factors involved in inflammation triggered by lipopolysaccharides (LPS) from P. aeruginosa, K. pneumoniae and E. coli. Sixteen cytokines and other major agents involved in inflammation were analyzed in macrophages and bronchial cells after stimulation with LPS and incubation with SET-M33...
October 7, 2016: Journal of Biological Chemistry
Peng Sang, Yan Shi, Peng Teng, Annie Cao, Hai Xu, Qi Li, Jianfeng Cai
Antibiotic resistance is one of the biggest public concerns in the 21st century. Host-defense peptides (HDPs) can potentially mitigate the problem through the disruption of bacterial membranes; however, they suffer from moderate activity and low stability. We recently developed a new class of peptidomimetics termed "AApeptides". This class of peptidomimetics can mimic the mechanism of action of HDPs, and effectively arrest the growth of multidrug resistant Gram-positive and Gram-negative bacteria. As they are built on unnatural backbone, they are highly resistant to proteolytic degradation...
October 18, 2016: Current Topics in Medicinal Chemistry
Tereza Tůmová, Lenka Monincová, Václav Čeřovský, Václav Kašička
Capillary electrophoresis (CE) was employed for the determination of thermodynamic acidity constants (pKa ) and actual ionic mobilities of polycationic antimicrobial peptides (AMPs). The effective electrophoretic mobilities of AMPs were measured by CE in a series of the background electrolytes within a wide pH range (2.00-12.25), at constant ionic strength (25 mM) and ambient temperature, using polybrene coated fused silica capillaries to suppress sorption of cationic AMPs to the capillary wall. Eventually, Haarhoff-Van der Linde peak fitting function was used for the determination of correct migration times of some AMPs peaks that were distorted by electromigration dispersion...
October 19, 2016: Electrophoresis
XianJun Yuan, AiYou Wen, Seare T Desta, ZhiHao Dong, Tao Shao
BACKGROUND: Short-chain fatty salts have been widely used as food and forage preservatives because of their antimicrobial properties. This study evaluated the effects of 4 chemical compounds with antimicrobial property on nitrogen transformations and intrinsic protease activity of alfalfa silage. RESULTS: Potassium diformate and formic acid rapidly reduced silage pH. Silages treated with sodium diacetate (SD) and calcium propionate (CAP) had higher final peptide N concentrations than other silage...
October 18, 2016: Journal of the Science of Food and Agriculture
Myung-Shik Lee
Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet...
September 2016: Journal of Hypertension
Zohaib Khurshid, Mustafa Naseem, Zeeshan Sheikh, Shariq Najeeb, Sana Shahab, Muhammad Sohail Zafar
Antimicrobial peptides (AMPs) are a wide-ranging class of host-defense molecules that act early to contest against microbial invasion and challenge. These are small cationic peptides that play an important in the development of innate immunity. In the oral cavity, the AMPs are produced by the salivary glands and the oral epithelium and serve defensive purposes. The aim of this review was to discuss the types and functions of oral AMPs and their role in combating microorganisms and infections in the oral cavity...
September 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Zhong-Guo Shan, Ke-Xin Zhu, Fang-Yi Chen, Jie Liu, Bei Chen, Kun Qiao, Hui Peng, Ke-Jian Wang
A new gene homologous to the reported antimicrobial peptide (AMP) hyastatin from Hyas araneus was screened in the SSH library constructed from the hemocytes of Scylla paramamosain, and named SpHyastatin. In vivo study showed that SpHyastatin was predominantly expressed in hemocytes of S. paramamosain. With the challenge of either Vibrio parahaemolyticus or lipopolysaccharide (LPS), SpHyastatin showed a positive response, meaning that it was probably involved in the immune reaction against bacterial infection in vivo...
October 14, 2016: Fish & Shellfish Immunology
De-Mei Meng, Jing-Fang Zhao, Xiao Ling, Hong-Xia Dai, Ya-Jun Guo, Xiao-Fang Gao, Bin Dong, Zi-Qi Zhang, Xin Meng, Zhen-Chuan Fan
The antimicrobial peptide PaDef was isolated from Mexican avocado fruit and was reported to inhibit the growth of Escherichia coli and Staphylococcus aureus in 2013. In this study, an N-terminal 6 × His tagged recombinant PaDef (rPaDef) with a molecular weight of 7.5 KDa, for the first time, was expressed as a secreted peptide in Pichia pastoris. The optimal culture condition for rPaDef expression was determined to be incubation with 1.5% methanol for 72 h at 28 °C under pH 6.0. Under this condition, the amount of the rPaDef accumulation reached as high as 79...
October 11, 2016: Protein Expression and Purification
Michele Miraglia Del Giudice, Annalisa Allegorico
The role of vitamin D in calcium and phosphate homeostasis is well known; however, in addition to traditional functions, vitamin D modulates a variety of processes, and evidence shows that it has an important role in different allergic diseases such as asthma, atopic dermatitis, and food allergy. Vitamin D acts by binding to the vitamin D receptor, which is present in a variety of tissues; for this reason it is considered a hormone. One of the most important functions is to modulate the immune system response, both innate and adaptive, by suppressing Th2-type response and increasing natural killer cells...
November 2016: Journal of Clinical Gastroenterology
Brian Murray, C Seth Pearson, Alexa Aranjo, Dinesh Cherupalla, Georges Belfort
As pathogenic bacteria become resistant to traditional antibiotics, alternate approaches such as designing and testing new potent selective antimicrobial peptides (AMP) are increasingly attractive. However, while much is known regarding the relationship between AMP sequence and potency, less research has focused on developing links between AMP properties, such as design and structure, with mechanism. Here we use four natural AMPs of varying known secondary structures and mechanisms of lipid bilayer disruption as controls to determine the mechanisms of four rationally designed AMPs with similar secondary structures and rearranged amino acid sequences...
October 13, 2016: Journal of Biological Chemistry
Mi Ok Lee, Hyun-Jun Jang, Deivendran Rengaraj, Seo-Yeong Yang, Jae Yong Han, Susan J Lamont, James E Womack
BACKGROUND: Host defence peptides are a diverse group of small, cationic peptides and are important elements of the first line of defense against pathogens in animals. Expression and functional analysis of host defense peptides has been evaluated in chicken but there are no direct, comprehensive comparisons with all gene family and individual genes. RESULTS: We examined the expression patterns of all known cathelicidins, β-defensins and NK-lysin in multiple selected tissues from chickens...
October 13, 2016: BMC Veterinary Research
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