A Simple Platform for the Rapid Development of Antimicrobials

Johnston, Stephen Albert; Domenyuk, Valeriy; Gupta, Nidhi; Batista, Milene Tavares; Lainson, John C.; Zhao, Zhan; Lusk, Joel F.; Loskutov, Andrey; Cichacz, Zbigniew A.; Stafford, Phillip; Legutki, Joseph Barten; Diehnelt, Chris W.

doi:10.1038/s41598-017-17941-7

Cited by 7 publications

(5 citation statements)

References 40 publications

(62 reference statements)

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“…Since these peptides are often very small and lack long-distance contacts that enforce specific 3D conformations, we wanted to explore how our models perform on these small structures. We compared the end-to-end distance of 3 hemagglutinin binding peptides 62 simulated in our ANM model, the ANMT model, and another popular coarse-grained protein model, AWSEM-MD. 37 Fig.…”

Section: Peptidesmentioning

confidence: 99%

Coarse-grained nucleic acid–protein model for hybrid nanotechnology

2021

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Section: Peptidesmentioning

confidence: 99%

Coarse-grained nucleic acid–protein model for hybrid nanotechnology

2021

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“…Also important to this method’s success, the peptide libraries are random sequences, enabling screening and discovery of new, atypical, or novel cellular interactions with unique mechanisms of action. Third, the diverse phenotypic screening approach is adaptable for different microorganisms. ,, Finally, the large number of replicate microarrays produced with the photolithographic synthetic approach empowers experimental screening designs with large numbers of replicates or screening conditions. These important features and flexibility enable the design of screens that produce viable hits, even for challenging organisms, such as Mabs .…”

Section: Discussionmentioning

confidence: 99%

“…Peptides are 17-mers and are synthesized from 15 different amino acids, including d -versions of Lys, Arg, Ala, Leu, and Trp. Previously, we developed an AMP discovery method using spotted peptide microarrays of 10,000 peptides to identify peptides that bind to targeted bacteria. − In this study, a 125,000 HD peptide microarray was used to screen for peptides with in vitro binding activity against Mabs S and R morphotypes. We then evaluated the activity of candidate peptides using a series of microdilution antimicrobial susceptibility assays performed in three culture media with and without a chelating agent.…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Screening Identifies Synthetic Peptides with Antibacterial Activity against Mycobacterium abscessus and Serum Stability

et al. 2022

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The rise in antibiotic resistance in bacteria has spawned new technological approaches for identifying novel antimicrobials with narrow specificity. Current antibiotic treatment regimens and antituberculosis drugs are not effective in treating Mycobacterium abscessus . Meanwhile, antimicrobial peptides are gaining prominence as alternative antimicrobials due to their specificity toward anionic bacterial membranes, rapid action, and limited development of resistance. To rapidly identify antimicrobial peptide candidates, our group has developed a high-density peptide microarray consisting of 125,000 random synthetic peptides screened for interaction with the mycobacterial cell surface of M. abscessus morphotypes. From the array screening, peptides positive for interaction were synthesized and their antimicrobial activity was validated. Overall, six peptides inhibited the M. abscessus smooth morphotype (IC 50 = 1.7 μM for all peptides) and had reduced activity against the M. abscessus rough morphotype (IC 50 range: 13–82 μM). Peptides ASU2056 and ASU2060 had minimum inhibitory concentration values of 32 and 8 μM, respectively, against the M. abscessus smooth morphotype. Additionally, ASU2060 (8 μM) was active against Escherichia coli , including multidrug-resistant E. coli clinical isolates, Pseudomonas aeruginosa , and methicillin-resistant Staphylococcus aureus . ASU2056 and ASU2060 exhibited no significant hemolytic activity at biologically relevant concentrations, further supporting these peptides as promising therapeutic candidates. Moreover, ASU2060 retained antibacterial activity after preincubation in human serum for 24 h. With antimicrobial resistance on the rise, methods such as those presented here will streamline the peptide discovery process for targeted antimicrobial peptides.

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“…Betanzos et al, 2009 using luminescent LPS-quantum dots from O111:B4 and O55:B5 serotypes of E. coli revealed that peptides binding to E.coli LPS were highly enriched in aromatic and cationic amino acids and most inhibited growth [51]. Johnston et al, 2017 screened a range of pathogens (10 viruses and 11 bacteria) against a library of 10,000 peptides to identify shared and specific pathogen binding peptides that were used for the development of a pathogen binding 100-peptide microarray [52].…”

Section: Plos Onementioning

confidence: 99%

Scoping review of the applications of peptide microarrays on the fight against human infections

et al. 2022

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Introduction This scoping review explores the use of peptide microarrays in the fight against infectious diseases. The research domains explored included the use of peptide microarrays in the mapping of linear B-cell and T cell epitopes, antimicrobial peptide discovery, immunosignature characterisation and disease immunodiagnostics. This review also provides a short overview of peptide microarray synthesis. Methods Electronic databases were systematically searched to identify relevant studies. The review was conducted using the Joanna Briggs Institute methodology for scoping reviews and data charting was performed using a predefined form. The results were reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Results Ninety-five articles from 103 studies were included in the final data charting process. The majority (92. 0%) of the articles were published during 2010–2020 and were mostly from Europe (44.2%) and North America (34.7%). The findings were from the investigation of viral (45.6%), bacterial (32. 0%), parasitic (23.3%) and fungal (2. 0%) infections. Out of the serological studies, IgG was the most reported antibody type followed by IgM. The largest portion of the studies (77.7%) were related to mapping B-cell linear epitopes, 5.8% were on diagnostics, 5.8% reported on immunosignature characterisation and 8.7% reported on viral and bacterial cell binding assays. Two studies reported on T-cell epitope profiling. Conclusion The most important application of peptide microarrays was found to be B-cell epitope mapping or antibody profiling to identify diagnostic and vaccine targets. Immunosignatures identified by random peptide microarrays were found to be applied in the diagnosis of infections and interrogation of vaccine responses. The analysis of the interactions of random peptide microarrays with bacterial and viral cells using binding assays enabled the identification of antimicrobial peptides. Peptide microarray arrays were also used for T-cell linear epitope mapping which may provide more information for the design of peptide-based vaccines and for the development of diagnostic reagents.

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A Simple Platform for the Rapid Development of Antimicrobials

Cited by 7 publications

References 40 publications

Coarse-grained nucleic acid–protein model for hybrid nanotechnology

Coarse-grained nucleic acid–protein model for hybrid nanotechnology

High-Throughput Screening Identifies Synthetic Peptides with Antibacterial Activity against Mycobacterium abscessus and Serum Stability

Scoping review of the applications of peptide microarrays on the fight against human infections

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