Next-Generation Antimicrobial Discovery through Bacterial Self-Screening of Surface-Displayed Peptide Libraries
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA371422 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Peptides have great potential to combat antibiotic resistance. While many platforms can screen peptides for their ability to bind to target cells, there are virtually no platforms that directly assess the functionality of peptides. This limitation is exacerbated when identifying antimicrobial peptides, since the phenotype, death, selects against itself, and has caused a scientific bottleneck confining research to only a few naturally occurring classes of antimicrobial peptides. We have used this seeming dissonance to develop Surface Localized Antimicrobial displaY (SLAY); a platform that allows screening of unlimited numbers of peptides of any length, composition, and structure in a single tube for antimicrobial activity. Using SLAY, we screened ~800,000 random peptide sequences for antimicrobial function and identified thousands of active sequences doubling the number of known antimicrobial sequences. SLAY hits present with different potential mechanisms of peptide action and access to areas of antimicrobial physicochemical space beyond what nature has evolved.
2018-01-03 | GSE94530 | GEO
Project description:Peptides have great potential to combat antibiotic resistance. While many platforms can screen peptides for their ability to bind to target cells, there are virtually no platforms that directly assess the functionality of peptides. This limitation is exacerbated when identifying antimicrobial peptides, since the phenotype, death, selects against itself, and has caused a scientific bottleneck confining research to only a few naturally occurring classes of antimicrobial peptides. We have used this seeming dissonance to develop Surface Localized Antimicrobial displaY (SLAY); a platform that allows screening of unlimited numbers of peptides of any length, composition, and structure in a single tube for antimicrobial activity. Using SLAY, we screened ~800,000 random peptide sequences for antimicrobial function and identified thousands of active sequences doubling the number of known antimicrobial sequences. SLAY hits present with different potential mechanisms of peptide action and access to areas of antimicrobial physicochemical space beyond what nature has evolved.
2018-01-03 | GSE94529 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-01-03 | GSE94531 | GEO
Project description: Not available
| S-EPMC5786472 | biostudies-literature
Project description:We developed a surface-displayed library of 117 human antimicrobial peptides (AMPs) and over 3000 human AMP variants in a laboratory E. coli strain expressing PhoP and PhoQ from Salmonella Typhimurium. We used sort-seq (fluorescence-activated cell sorting followed by next-generation sequencing) to characterize PhoPQ activation by these surface-displayed AMPs.
2022-11-09 | GSE174191 | GEO
Project description: Not available
| S-EPMC3602187 | biostudies-literature
Project description:Staphylococcus aureus is a leading cause of hospital-associated infections. In addition, highly virulent strains of methicillin-resistant S. aureus (MRSA) are currently spreading outside health care settings. Survival in the human host is largely defined by the ability of S. aureus to resist mechanisms of innate host defense, of which antimicrobial peptides form a key part especially on epithelia and in neutrophil phagosomes. Here we demonstrate that the antimicrobial-peptide sensing system aps of the standard community-associated MRSA strain MW2 controls resistance to cationic antimicrobial peptides. The core of aps-controlled resistance mechanisms comprised the D-alanylation of teichoic acids (dlt operon), the incorporation of cationic lysyl-phosphatidylglycerol (L-PG) in the bacterial membrane (mprF), and the vraF/vraG putative antimicrobial peptide transporter. Further, the observed increased production of L-PG under the influence of cationic antimicrobial peptides was accompanied by the up-regulation of lysine biosynthesis. In noticeable difference to the aps system of S. epidermidis, only selected antimicrobial peptides strongly induced the aps response. Heterologous complementation with the S. epidermidis apsS gene indicated that this is likely caused by differences in the short extracellular loop of ApsS that interacts with the inducing antimicrobial peptide. Our study shows that the antimicrobial peptide sensor system aps is functional in the important human pathogen S. aureus, significant interspecies differences exist in the induction of the aps gene regulatory response, and aps inducibility is clearly distinguishable from effectiveness towards a given antimicrobial peptide. Keywords: Wild type control vs treated vs mutant
2008-04-07 | GSE8400 | GEO
Project description:Staphylococcus aureus is a leading cause of hospital-associated infections. In addition, highly virulent strains of methicillin-resistant S. aureus (MRSA) are currently spreading outside health care settings. Survival in the human host is largely defined by the ability of S. aureus to resist mechanisms of innate host defense, of which antimicrobial peptides form a key part especially on epithelia and in neutrophil phagosomes. Here we demonstrate that the antimicrobial-peptide sensing system aps of the standard community-associated MRSA strain MW2 controls resistance to cationic antimicrobial peptides. The core of aps-controlled resistance mechanisms comprised the D-alanylation of teichoic acids (dlt operon), the incorporation of cationic lysyl-phosphatidylglycerol (L-PG) in the bacterial membrane (mprF), and the vraF/vraG putative antimicrobial peptide transporter. Further, the observed increased production of L-PG under the influence of cationic antimicrobial peptides was accompanied by the up-regulation of lysine biosynthesis. In noticeable difference to the aps system of S. epidermidis, only selected antimicrobial peptides strongly induced the aps response. Heterologous complementation with the S. epidermidis apsS gene indicated that this is likely caused by differences in the short extracellular loop of ApsS that interacts with the inducing antimicrobial peptide. Our study shows that the antimicrobial peptide sensor system aps is functional in the important human pathogen S. aureus, significant interspecies differences exist in the induction of the aps gene regulatory response, and aps inducibility is clearly distinguishable from effectiveness towards a given antimicrobial peptide. Keywords: Wild type control vs treated vs mutant Wild type untreated in triplicate is compared to wild type treated in triplicate along with three mutants in triplicate with and without treatment of indolicidin, totalling 30 samples
2008-04-06 | E-GEOD-8400 | biostudies-arrayexpress
Project description:The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility, while some regulate the microbiota. We report peptide YY (PYY1-36), but not endocrine PYY3-36, is an antimicrobial peptide (AMP) expressed by gut epithelial Paneth Cells (PC). PC-PYY has limited antibacterial activity, but shows selective activity against virulent hyphal, but not yeast forms, of Candida albicans. 5 PC-PYY is a cationic molecule that interacts with the anionic surfaces of fungal hyphae to cause membrane disruption and transcriptional reprogramming to maintain the yeast phenotype of the fungus. PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity. Hence, PC-PYY acts as a selective antifungal AMP that contributes to the maintenance of gut fungal commensalism.
2024-02-28 | GSE229566 | GEO
Project description:Proteome-derived peptide libraries are a powerful tool for the investigation of protease specificity, conventionally involving the biotinylation of cleavage products to enable for their enrichment. Here we present a modified strategy for protease specificity profiling using proteome-derived peptide libraries in a tag-free manner. In comparison to the original method the new protocol is faster, avoids cost- and time-intensive enrichment steps, and enables probing for lysine selectivity. In the new workflow, peptide libraries are generated by endoproteolytic digestion of proteomes without chemical modification of primary amines prior to exposure to a protease under investigation. After incubation with the test protease, treated and control library are differentially labeled using stable isotopes by means of reductive dimethylation. Upon analysis by liquid chromatography mass spectrometry, cleavage products of the test protease appear as peptides enriched for the respective isotopic label. With “PICS 2.0” we identified more than 2800 cleavage sites in five specificity experiments for four proteases, including trypsin, caspase-3, and chlamydial protease-like activity factor (CPAF). Hence, this method is a valuable addition to the different strategies currently employed for specificity profiling of proteases
2016-05-02 | PXD002785 | Pride