Antimicrobial peptides are found in both myeloid cells and mucosal tissues of many vertebrates invertebrates. These predicted to operate as a first-line host defense mechanism exerting broad-spectrum activity against pathogenic bacteria, fungi, parasites, enveloped viruses. We report the characterization novel 25-residue linear antimicrobial peptide skin mucous secretions winter flounder (Pleuronectes americanus). This was purified through multiple chromatographic methods obtain single peak...

Recent reports highlighted the chemotactic activities of antimicrobial peptide defensins whose structure, charge, and size resemble chemokines. By assaying representative members four known families chemokines we explored obverse: whether some exert activity. In a radial diffusion assay, only recombinant monokine induced by IFN-gamma (MIG/CXCL9), IFN-gamma-inducible protein 10 kDa (IP-10/CXCL10), IFN-inducible T cell alpha chemoattractant (I-TAC/CXCL11), tripeptide motif Glu-Leu-Arg (ELR)(-)...

Human bone marrow expresses a pseudogene that encodes an antimicrobial peptide homologous to rhesus monkey circular minidefensins (θ-defensins). We prepared the putative ancestral human by solid-phase synthesis and named it “retrocyclin.” Retrocyclin did not cause direct inactivation of HIV-1, its modest antibacterial properties resembled those homologs. Nevertheless, retrocyclin had remarkable ability inhibit proviral DNA formation protect immortalized primary CD4 + lymphocytes from in...

ABSTRACT Minimally manipulated nasal secretions, an accessible form of airway surface fluid, were tested against indigenous and added bacteria by using CFU assays. Antimicrobial activity was found to vary between donors with different target markedly diminished dilution the secretions. Donor-to-donor differences in electrophoresis patterns secretions sodium dodecyl sulfate-polyacrylamide gel (PAGE) acid urea-PAGE analyses readily observed, suggesting that polymorphic genes encode secreted...

ABSTRACT Nasal carriage of Staphylococcus aureus has been identified as a risk factor for community-acquired and nosocomial infections. We screened 230 donors diverse ethnic socioeconomic backgrounds 62 (27%) whose nasal secretions were colonized by S . In 18 in whom the various regions luminal surface separately sampled, predominant region colonization was moist squamous epithelium on septum adjacent to ostium. fluid from carriers defective killing endogenous carrier isolates but not...

In a search for direct evidence leading to the biological relevance of airway secretions in innate host defense, we characterized antibacterial function cationic polypeptides within minimally manipulated nasal fluid. this study, show that antimicrobial are responsible most bactericidal activity whole The removal using cation-exchange resin ablated fluid against Escherichia coli, Listeria monocytogenes, and Pseudomonas aeruginosa. By novel proteomic approach, identified dozen peptides...

Abstract θ-Defensins are circular octadecapeptides that contain an internal tridisulfide ladder. Because retrocyclin-1, ancestral hominid θ-defensin, can protect human cells in vitro from infection by T- and M-tropic strains of HIV-1, we used surface plasmon resonance techniques to study its binding glycoproteins glycolipids implicated HIV-1 entry. Retrocyclin-1 bound with high affinity gp120 (Kd, 35.4 nM), CD4 31 galactosylceramide 24.1 nM). Neither a form retrocyclin without ladder nor...

Abstract θ-Defensins are lectin-like, cyclic octadecapeptides found in the leukocytes of nonhuman primates. They also homologues more familiar α-defensins expressed by humans and certain other mammals. This study compares ability six θ-defensins (hominid retrocyclins 1–3 rhesus 1–3) four human (human neutrophil peptides (HNPs) 1–4) to bind gp120 CD4. In addition, we compared these HNP-1 protect J53-BL cells (an indicator cell line) from primary HIV-1 isolates that varied subtype coreceptor...

Type I interferons (IFNs) inhibit viral replication and cell growth enhance the immune response, therefore have many clinical applications. IFN-alpha2b ranks third in world market use for a biopharmaceutical, behind only insulin erythropoietin. The average annual cost of treatment hepatitis C infection is $26,000, unavailable to majority patients developing countries. Therefore, we expressed tobacco chloroplasts, transgenic lines were grown field after obtaining United States Department...

Background RC-101 is a congener of the antiretroviral peptide retrocyclin, which we and others have reported active against clinical HIV-1 isolates from all major clades, does not hemagglutinate, non-toxic non-inflammatory in cervicovaginal cell culture. Herein, film-formulated was assessed for its antiviral activity vitro, safety vivo, retention cervix vagina, ability to remain SHIV after intravaginal application macaques. Methodology/Principal Findings formulated as quick-dissolving film...

ABSTRACT Antimicrobial peptides are proposed to act as the first line of mucosal host defense by exerting broad-spectrum microbicidal activity against pathogenic microbes. Pleurocidin, a new 25-residue linear antimicrobial peptide, was recently isolated from skin secretions winter flounder ( Pleuronectes americanus ). The present study identifies cDNA and gene encoding pleurocidin. pleurocidin comprises four exons. Its upstream region demonstrates consensus binding sequences for...

Abstract Mucosal surfaces of the vagina are portals for heterosexual transmission HIV-1 and therefore play a fundamental role in pathogenesis primary infection. In search direct biological evidence human vaginal fluid innate host defense, we characterized anti-HIV-1 function cationic polypeptides within minimally manipulated fluid. current study revealed that confers intrinsic properties against both X4 R5 strains could protect infection reduce proviral genome integration organotypic...

Retrocyclin is a circular antimicrobial 18-residue peptide encoded in the human genome by θ-defensin pseudogene. In genome, gene for retrocyclin inactivated an in-frame stop codon its signal sequence but mature coding intact. The corresponding to processed retrocyclin, generated solid phase synthesis, inhibited replication of R5 and X4 strains HIV-1 cells. Luciferase reporter virus Vpr-BLaM entry assays were used demonstrate that specifically blocked at entry. Surface plasmon resonance...

Retrocyclin-1, a -defensin, protects target cells from human immunodeficiency virus, type 1 (HIV-1) by preventing viral entry. To delineate its mechanism, we conducted fusion assays between susceptible and effector that expressed HIV-1 Env. Retrocyclin-1 (4 microm) completely blocked mediated Envs used CXCR4 or CCR5 but had little effect on cell HIV-2 simian virus Envs. inhibited Env-mediated without impairing the lateral mobility of CD4, it CD4-deficient with bearing CD4-independent Thus,...

Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective this study was to examine effect 14 daily applications 0.5% PRO 2000 placebo gel on immunity and intrinsic antimicrobial activity.A randomized, prospective, double-blind, placebo-controlled conducted among 24 healthy, abstinent women. Levels cytokines, chemokines, defensins, other protective factors activity were determined in cervicovaginal lavage...

Abstract Background Estimates of relationships among Staphylococcus species have been hampered by poor and inconsistent resolution phylogenies based largely on single gene analyses incorporating only a limited taxon sample. As such, the evolutionary hierarchical classification schemes not confidently established. Here, we address these points through DNA sequence data from multiple loci (16S rRNA gene, dnaJ, rpoB, tuf fragments) using Bayesian maximum likelihood phylogenetic approaches that...

Human alpha and beta defensins contribute substantially to innate immune defenses against microbial viral infections. Certain nonhuman primates also produce theta-defensins—18 residue cyclic peptides that act as HIV-1 entry inhibitors. Multiple human theta-defensin genes exist, but they harbor a premature termination codon blocks translation. Consequently, the theta-defensins (retrocyclins) encoded within genome are not expressed peptides. In vivo production of in rhesus macaques involves...

Bacterial vaginosis (BV) is the most commonly treated female reproductive tract affliction, characterized by displacement of healthy lactobacilli an overgrowth pathogenic bacteria. BV can contribute to inflammation, preterm birth, and susceptibility sexually transmitted infections. As bacteria responsible for pathogenicity their interactions with host immunity are not understood, we sought evaluate effects BV-associated on epithelia. Here have interaction between measuring cytokine defensin...

Abstract One of the major roles seminal plasma is to provide antimicrobial protection for spermatozoa in female reproductive tract. We found that bactericidal activity was highest after resolution clot and this antibacterial subsequently became greatly diminished. The derived from peptides generated by fragmentation semenogelins while semenogelin holoproteins displayed no activity. After ejaculation semenogelin-derived were fragmented smaller fragments over time thereby lost This paralleled...