scholarly journals Developmental switch of intestinal antimicrobial peptide expression

2008 ◽  
Vol 205 (1) ◽  
pp. 183-193 ◽  
Author(s):  
Sandrine Ménard ◽  
Valentina Förster ◽  
Michael Lotz ◽  
Dominique Gütle ◽  
Claudia U. Duerr ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
High Performance ◽  
Bacterial Colonization ◽  
Paneth Cell ◽  
Active Form ◽  
Constitutive Expression ◽  
Postnatal Period ◽  
Enteric Infection ◽  
Immune Effector ◽  
Developmental Switch

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.

scholarly journals Anti-Fibrotic Activity of an Antimicrobial Peptide in a Drosophila Model

2021 ◽  
pp. 1-15
Author(s):  
Dilan Khalili ◽  
Christina Kalcher ◽  
Stefan Baumgartner ◽  
Ulrich Theopold
Keyword(s):  
Antimicrobial Peptide ◽  
Cell Polarity ◽  
Active Form ◽  
Ectopic Expression ◽  
Secretory Activity ◽  
Ras Oncogene ◽  
Apicobasal Polarity ◽  
Pathological Conditions ◽  
Extracellular Matrix Components ◽  
Matrix Components

Fibrotic lesions accompany several pathological conditions, including tumors. We show that expression of a dominant-active form of the Ras oncogene in <i>Drosophila</i> salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components, including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apicobasal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide drosomycin (Drs), which also restores the secretory activity of the SGs. In addition to extracellular matrix components, both Drs and F-actin localize to fibrotic lesions.

Clindamycin-loaded titanium prevents implant-related infection through blocking biofilm formation

2021 ◽  
pp. 088532822110511
Author(s):  
Youbin Li ◽  
Shaochuan Wang ◽  
Shidan Li ◽  
Jun Fei
Keyword(s):  
Surface Modification ◽  
Rat Model ◽  
Biofilm Formation ◽  
High Performance ◽  
Bacterial Colonization ◽  
Tissue Homogenate ◽  
Tartrate Resistant Acid Phosphatase ◽  
Layer By Layer

Implant-related infection is a disastrous complication. Surface modification of titanium is considered as an important strategy to prevent implant-related infection. However, there is no recognized surface modification strategy that can be applied in clinic so far. We explored a new strategy of coating. The clindamycin-loaded titanium was constructed by layer-by-layer self-assembly. The release of clindamycin from titanium was detected through high performance liquid chromatography. Different titanium was co-cultured with Staphylococcus aureus for 24 h in vitro, then the effect of different titanium on bacterial colonization and biofilm formation was determined by spread plate method and scanning electron microscopy. Cytotoxicity and cytocompatibility of clindamycin-loaded titanium on MC3T3-E1 cells were measured by CCK8. The antibacterial ability of clindamycin-loaded titanium in vivo was also evaluated using a rat model of osteomyelitis. The number of osteoclasts in bone defect was observed by tartrate-resistant acid phosphatase staining. Bacterial burden of surrounding tissues around the site of infection was calculated by tissue homogenate and colony count. Clindamycin-loaded titanium could release clindamycin slowly within 160 h. It reduced bacterial colonization by three orders of magnitude compare to control ( p < .05) and inhibits biofilm formation in vitro. Cells proliferation and adhesion were similar on three titanium surfaces ( p > .05). In vivo, clindamycin-loaded titanium improved bone healing, reduced microbial burden, and decreased the number of osteoclasts compared control titanium in the rat model of osteomyelitis. This study demonstrated that clindamycin-loaded titanium exhibited good biocompatibility, and showed antibacterial activity both in vivo and in vitro. It is promising and might have potential for clinical application.

Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice

2004 ◽  
Vol 286 (6) ◽  
pp. G1050-G1058 ◽  
Author(s):  
Lane L. Clarke ◽  
Lara R. Gawenis ◽  
Emily M. Bradford ◽  
Louise M. Judd ◽  
Kathryn T. Boyle ◽  
...  
Keyword(s):  
Northern Blot Analysis ◽  
Clinical Symptoms ◽  
Bacterial Colonization ◽  
Paneth Cell ◽  
Light And Electron Microscopy ◽  
Paneth Cells ◽  
Real Time Quantitative Pcr ◽  
Granule Morphology ◽  
Mouse Intestine ◽  
Osmotic Laxative

Paneth cells of intestinal crypts contribute to host defense by producing antimicrobial peptides that are packaged as granules for secretion into the crypt lumen. Here, we provide evidence using light and electron microscopy that postsecretory Paneth cell granules undergo limited dissolution and accumulate within the intestinal crypts of cystic fibrosis (CF) mice. On the basis of this finding, we evaluated bacterial colonization and expression of two major constituents of Paneth cells, i.e., α-defensins (cryptdins) and lysozyme, in CF murine intestine. Paneth cell granules accumulated in intestinal crypt lumens in both untreated CF mice with impending intestinal obstruction and in CF mice treated with an osmotic laxative that prevented overt clinical symptoms and mucus accretion. Ultrastructure studies indicated little change in granule morphology within mucus casts, whereas granules in laxative-treated mice appear to undergo limited dissolution. Protein extracts from CF intestine had increased levels of processed cryptdins compared with those from wild-type (WT) littermates. Nonetheless, colonization with aerobic bacteria species was not diminished in the CF intestine and oral challenge with a cryptdin-sensitive enteric pathogen, Salmonella typhimurium, resulted in greater colonization of CF compared with WT intestine. Modest downregulation of cryptdin and lysozyme mRNA in CF intestine was shown by microarray analysis, real-time quantitative PCR, and Northern blot analysis. Based on these findings, we conclude that antimicrobial peptide activity in CF mouse intestine is compromised by inadequate dissolution of Paneth cell granules within the crypt lumens.

scholarly journals RELATION BETWEEN BACTERIAL COLONIZATION IN LUNGS AND LEVELS OF 25-HYDROXYVITAMIN D AND ANTIMICROBIAL PEPTIDE LL-37 IN CHILDREN WITH CYSTIC FIBROSIS

InterConf ◽  
2021 ◽  
pp. 278-282
Author(s):  
Veronika Dudnyk ◽  
Valeriia Demianyshyna
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Peptide ◽  
Bacterial Colonization ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
25 Hydroxycholecalciferol

The aim of the study was to assess the bacterial colonization in lungs of children with cystic fibrosis based on the antimicrobial peptide cathelicidin and 25-hydroxycholecalciferol in the serum. Study showed significant correlation between P. aeruginosa infection and cathelicidin and 25-hydroxycholecalciferol levels.

scholarly journals Peptide YY: a novel Paneth cell antimicrobial peptide that maintains fungal commensalism

2020 ◽  
Author(s):  
Joseph F. Pierre ◽  
Diana La Torre ◽  
Ashley Sidebottom ◽  
Amal Kambal ◽  
Xiaorong Zhu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Antifungal Activity ◽  
Crohn's Disease ◽  
Antimicrobial Peptide ◽  
Peptide Yy ◽  
Secretory Granules ◽  
Paneth Cell ◽  
List Type ◽  
Fungal Virulence ◽  
Intestinal Microbes

SUMMARYPerturbed interactions between the intestinal microbes and host correlate with emergence of fungal virulence. Here we report a previously unknown role for peptide YY (PYY), a described endocrine molecule, as an antimicrobial peptide (AMP) expressed by gut immune epithelial Paneth Cells (PC). PC-PYY differs from other AMPs, including lysozyme, because of limited antibacterial activity, packaging in discrete secretory granules, and selective antifungal activity to virulent hyphae, but not yeast forms of Candida albicans. The latter action is through binding of cationic PC-PYY to the anionic hyphal surface, resulting in membrane disruption and killing. PC-PYY is compartmentalized to surface mucus, which optimizes activity and prevents conversion to endocrine PYY by dipeptidyl peptidase-IV (DPP-IV). We conclude PC-PYY is a unique AMP with selective antifungal activity that maintains gut fungal commensalism. Compromised PC-PYY action from PC dysfunction and/or mucus depletion in ileal Crohn’s disease may initiate or contribute to disease via fungal pathogenesis.Highlights⍰ Paneth Cell PYY (PC-PYY) is an antimicrobial peptide that differs from endocrine-PYY⍰ PC-PYY is a selective anti-fungal peptide, targeting the virulent form of C. albicans⍰ PC-PYY is separately packaged, retained by mucus, and released by C. albicans hyphae⍰ PC-PYY is proposed as essential for maintenance of fungal commensalism in the gutGraphical AbstractModel for Paneth cell (PC) PYY action and regulation of fungal commensalisms and potential role in the pathogenesis of ileal Crohn’s Disease (iCD)(A) In a healthy ileum, commensal yeast reside and do not stimulate PYY1-36 release from PCs. (B) Increased virulent hyphae (purple hyphae) results in PYY1-36 release from crypt PCs into the mucus. Hyphae are targeted by PYY1-36 and killed (red hyphae) to manage the increased fungi community in gut. (C) In a diseased ileum such as iCD, hyphal load induces immune activation and increased inflammation through PC dysfunction (gray PCs) and decreased PYY1-36 release or mucus depletion and PC dysfunction.

scholarly journals Multilayer Polyelectrolyte Films Functionalized by Insertion of Defensin: a New Approach to Protection of Implants from Bacterial Colonization

2004 ◽  
Vol 48 (10) ◽  
pp. 3662-3669 ◽  
Author(s):  
O. Etienne ◽  
C. Picart ◽  
C. Taddei ◽  
Y. Haikel ◽  
J. L. Dimarcq ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Micrococcus Luteus ◽  
Bacterial Colonization ◽  
Streaming Potential ◽  
Multilayer Films ◽  
Microbial Infection ◽  
Host Protection ◽  
New Strategy ◽  
Local Host ◽  
Positively Charged

ABSTRACT Infection of implanted materials by bacteria constitutes one of the most serious complications following prosthetic surgery. In the present study, we developed a new strategy based on the insertion of an antimicrobial peptide (defensin from Anopheles gambiae mosquitoes) into polyelectrolyte multilayer films built by the alternate deposition of polyanions and polycations. Quartz crystal microbalance and streaming potential measurements were used to follow step by step the construction of the multilayer films and embedding of the defensin within the films. Antimicrobial assays were performed with two strains: Micrococcus luteus (a gram-positive bacterium) and Escherichia coli D22 (a gram-negative bacterium). The inhibition of E. coli D22 growth at the surface of defensin-functionalized films was found to be 98% when 10 antimicrobial peptide layers were inserted in the film architecture. Noticeably, the biofunctionalization could be achieved only when positively charged poly(l-lysine) was the outermost layer of the film. On the basis of the results of bacterial adhesion experiments observed by confocal or electron microscopy, these observations could result from the close interaction of the bacteria with the positively charged ends of the films, which allows defensin to interact with the bacterial membrane structure. These results open new possibilities for the use of such easily built and functionalized architectures onto any type of implantable biomaterial. The modified surfaces are active against microbial infection and represent a novel means of local host protection.

Hyperphenylalaninemia Due to Dihydropteridine Reductase Deficiency: Diagnosis by Measurement of Oxidized and Reduced Pterins in Urine

PEDIATRICS ◽  
1980 ◽  
Vol 65 (4) ◽  
pp. 806-810
Author(s):  
Sheldon Milstien ◽  
Seymour Kaufman ◽  
George K. Summer
Keyword(s):  
High Performance ◽  
Active Form ◽  
High Performance Liquid Chromatographic ◽  
Dihydropteridine Reductase ◽  
Normal Children ◽  
Reductase Deficiency ◽  
Cultured Skin ◽  
Aromatic Amino Acid Hydroxylase ◽  
Liver Biopsies ◽  
Liquid Chromatographic

Hyperphenylalaninemia due to dihydropteridine reductase deficiency results from the inability to maintain the aromatic amino acid hydroxylase cofactor, tetrahydrobiopterin, in its reduced or active form. Diagnosis of the disease is usually made by direct enzymatic assay on liver biopsies or in cultured skin fibroblasts. Evidence is presented that normal children and classic phenylketonuric children excrete mainly tetrahy-drobiopterin in their urmnes, whereas children with dihydropteridine reductase deficiency excrete only oxidized forms of biopterin. Details of a rapid high performance liquid chromatographic assay for the measurement of the various forms of biopterin in urine are presented. This assay can be used to screen for suspected dihydropteridine reductase mutants.

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