1,721,022 research outputs found
ANTIMICROBIAL PEPTIDES FROM AMPHIBIAN SKIN: WHAT DO THEY TELL US?
No full textAmphibian skin secretions contain many biologically active compounds, such as biogenic
amines, complex alkaloids, or peptides. Within the latter class of molecules, a large number
of peptide antibiotics has been isolated and characterized from different amphibian species.
Antimicrobial peptides are considered the effector molecules of innate immunity, acting as a first
line of defense against bacterial infections, by perturbing the phospholipid bilayer of the target cell
membrane. These gene-encoded molecules are synthesized as inactive precursors and in several
cases their proparts were shown to have highly conserved structures. It has also been demonstrated
that the promoter regions of inducible peptide antibiotics are often regulated by the transcriptional
control machinery NF-kB/IkBa. In amphibia of Rana and Bombina genera, inhibition of transcription
of the genes encoding antimicrobial peptides has been obtained by glucocorticoid treatment,
which causes an increase of IkBa synthesis. Moreover, determination of the structure of a number
of genes coding for antimicrobial peptides in amphibia has actually shown that their promoter
regions contain recognition sites for nuclear factors
Resistance in Candida albicans: exploring the cell wall barrier by proteomics
Full text linkThe incidence of candidiasis has dramatically increased and bloodstream infections due to different species of
Candida are becoming a prime cause of morbidity and mortality in different types of immunocompromised patients.
Azole and echinocandin drug resistance accounts for the dramatic increase in incidence of nosocomial bloodstream
candidiasis found in recent years. Cell wall constitutes the barrier between the yeast and the host and resistant
strains change the proteome of this compartment. In the last decade different proteomic platforms have been
applied to study cell wall and markers of resistance to drugs have been pointed out. Modulation of these proteins
seem to suggest that although resistance is based on a specific mutation able to counteract the toxicity of the
antifungal drug, a set of other molecular modifications takes place contemporary or subsequently the establishment
of the resistance and seems to support the viability of the resistant yeast. Profiled proteins by proteomics may be
valuable in design therapy using classical antifungal along with complementary drugs able to abolish pathways that
strengthen the resistance and attenuate virulence of the mutated cell
Rab11A depletion in microglia-derived extracellular vesicle proteome upon beta-amyloid treatment
Full text linkMicroglia, the macrophage-like glial cells, behave as sentinels against exogenous pathogens invading the neural tissue. Their commitment is not only confined to the defensive function, but they also perform balancing trophic activities such as neuronal postnatal development, remodeling and pruning of synapses. Likewise, microglia-derived extracellular vesicles (EVs) can play strategic roles in maintaining a healthy brain by modulating neuronal activity and by controlling neurite outgrowth as well as innate immune response. Nevertheless, strong evidence also points to their role in the development of neurodegenerative pathologies such as Alzheimer's disease (AD). Here, we explored EV protein content released by BV2 microglial cells in a resting state and after stimulation with beta-amyloid peptides (Aβ), mimicking conditions occurring in AD. In the resting BV2 cells, we extended the list of proteins present in mouse microglia EV cargo with respect to those reported in the Vesiclepedia exosome database while, in amyloid-triggered microglia, we highlighted a pronounced drop in EV protein content. Focusing on Rab11A, a key factor in the recycling routes of amyloid species, we observed a dramatic decrease of this protein in Aβ-treated microglia EV cargo with respect to the EVs from the untreated sample. This decrease might affect the delivery of Rab11A to neurons thus increasing the harmful amyloid burden in neuronal cells that eventually may lead to their death. We tentatively proposed that alterations observed in EVs derived from Aβ-treated microglia may represent molecular features that, among others, shape the disease-associated microglial phenotype, a recently proposed subset of microglial population, present in neurodegenerative pathologies
Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence
Full text linkC. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality.C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality
Antibacterial and haemolytic peptides containing D-alloisoleucine from the skin of Bombina variegata
No full textA family of bombinin-related peptides is present in the skin of Bombina variegata. These peptides contain 27 residues with Gly as N-terminus and display antimicrobial activity. From sequence analysis of the cDNAs encoding for the corresponding peptide precursors, the presence of a novel 20-residue peptide with Ile as N-terminus was predicted. We have now purified a family of hydrophobic peptides named H1-H5, whose sequences correspond to the predicted peptide with some variability in positions 1, 2 and 8. In particular, H3-H5 contain a D-alloisoleucine residue in the second position. All these peptides display antibacterial and haemolytic activity
ANTIMICROBIAL PEPTIDES FROM SKIN SECRETIONS OF RANA ESCULENTA. MOLECULAR CLONING OF cDNAs ENCODING ESCULENTIN AND BREVININS AND ISOLATION OF NEW ACTIVE PEPTIDES
No full textThree cytolytic peptides, termed brevinin-1E, brevinin-2E, and esculentin, were isolated from skin secretions of the European frog Rana esculenta (Simmaco, M., Mignogna, G., Barra, D., and Bossa, F. (1993) FEBS Lett. 324, 159-161). Nucleotide sequence analysis of cDNAs coding for the corresponding precursors revealed that in all of them a single copy of the sequence of the mature peptide is present preceded by a dibasic cleavage site and followed by a stop codon. The signal peptides of these precursors show a clear homology to the corresponding region of the precursor of dermorphin, a neuropeptide occurring in the skin of amphibians of the subfamily Phyllomedusinae. Ten new peptides, ranging in size from 24 to 46 residues, all possessing an intramolecular disulfide bridge located at the carboxyl-terminal end, were isolated from skin secretions of R. esculenta. These peptides can be grouped into four subfamilies on the basis of their distinctive structural and/or functional properties. All of these new peptides have antimicrobial and/or hemolytic activities typical for the respective subfamily. In addition, we demonstrate that esculentin-1 also inhibits the growth of Pseudomonas aeruginosa, Candida albicans, and Saccharomyces cerevisiae
Occurrence and properties of glutathione S-transferases in phenol-degrading Pseudomonas strains
No full textPseudomonas sp. strains, able to degrade aromatic compounds such as phenol, were chosen to investigate the occurrence and characteristics of glutathione S-transferases (GSTs). Affinity chromatography purification showed the presence of at least one GST in each studied strain. The purified proteins exhibited a great variety in the N-terminal sequences and different enzyme activities with the standard GST substrates tested. Two Pseudomonas strains, M1 and CF600, were chosen to investigate the GST activities under different growth conditions. Therefore, cells were grown either on phenol or on different nonaromatic carbon sources in the presence and absence of increasing phenol concentrations. In strain M1 a strong correlation between the activities of the catechol 1,2-dioxygenase and GST was observed in all the tested conditions. Moreover, growth on different organic acids also affected GST activity levels, with a negative correlation with the specific growth rate determined by each substrate. These results suggest a possible function of GST as a response to specific metabolic conditions determined by phenol toxicity and/or catabolism and the metabolic status of the cells. The same experiments performed with the CF600 strain did not show induction of GST activity in any of the tested conditions, indicating that GST_CF600 probably has a different role in cell metabolism. Native gel electrophoresis gave indications that GST dimerization could be an important process in the modulation of GST activity. 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved
Novel antimicrobial peptides from skin secretion of the European frog Rana esculenta.
No full textThree antimicrobial peptides were isolated from skin secretion of the European frog, Rana esculenta. Two of them show similarity to brevinin-1 and brevinin-2, respectively, two antimicrobial peptides recently isolated from a Japanese frog [Morikawa, N., Hagiwara, K. and Nakajima, T. (1992) Biochem. Biophys. Res. Commun. 189, 184-190]. The third one, named esculentin, is 46 residues long and represents a different type of peptide. All these peptides have as a common motif an intramolecular disulfide bridge located at the COOH-terminal end. The peptides from R. esculenta show distinctive antibacterial activity against representative Gram-negative and Gram-positive bacterial species. In particular, esculentin is the most active against Staphylococcus aureus, and has a much lower hemolytic activity
OCCURENCE AND FUNCTION OF D-AMINO ACIDS-CONTAINING PEPTIDES AND PROTEINS: ANTIMICROBIAL PEPTIDES.
No full textAntimicrobial peptides are widely distributed in living organisms, where they represent a constitutive defence system acting as a first line of response against infections. The number of such peptides discovered has increased rapidly in the last few years, and more than 100 have been described from different sources. So far, antimicrobial peptides containing a D-amino acid have only been found in the skin secretions of frogs belonging to the genus Bombina. In the second position of the sequence of the mature peptides either D-alloisoleucine or D-leucine were detected. The D-amino acids are derived from the corresponding L forms by an as yet unknown posttranslational reaction
- …
