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(Re)Defining the proline-rich antimicrobial peptide family and the identification of putative new members
journal contributionposted on 2021-01-12, 01:56 authored by Nicholas Welch, W Li, MA Hossain, F Separovic, NM O'Brien-Simpson, JD Wade
© Copyright © 2020 Welch, Li, Hossain, Separovic, O'Brien-Simpson and Wade. As we rapidly approach a post-antibiotic era in which multi-drug resistant bacteria are ever-pervasive, antimicrobial peptides (AMPs) represent a promising class of compounds to help address this global issue. AMPs are best-known for their membrane-disruptive mode of action leading to bacteria cell lysis and death. However, many AMPs are also known to be non-lytic and have intracellular modes of action. Proline-rich AMPs (PrAMPs) are one such class, that are generally membrane permeable and inhibit protein synthesis leading to a bactericidal outcome. PrAMPs are highly effective against Gram-negative bacteria and yet show very low toxicity against eukaryotic cells. Here, we review both the PrAMP family and the past and current definitions for this class of peptides. Computational analysis of known AMPs within the DRAMP database (http://dramp.cpu-bioinfor.org/) and assessment of their PrAMP-like properties have led us to develop a revised definition of the PrAMP class. As a result, we subsequently identified a number of unknown and unclassified peptides containing motifs of striking similarity to known PrAMP-based DnaK inhibitors and propose a series of new sequences for experimental evaluation and subsequent addition to the PrAMP family.
NOBS is the recipient of NHMRC funding (APP1142472, APP1158841, APP1185426), ARC funding (DP160101312, LE200100163), Cancer Council Victoria funding (APP1163284), and Australian Dental Research. Funding for antimicrobial materials and research was also supported by the Centre for Oral Health Research at The Melbourne Dental School. JW is an NHMRC Principal Research Fellow (1117483). The studies undertaken in his laboratory were supported by an NHMRC Project grant (APP1158841). WL is the recipient of the 2019 Weary Dunlop Foundation grant and 2020 Early Career Researcher grant scheme of the University of Melbourne. Research at The Florey Institute of Neuroscience and Mental Health was supported by the Victorian Government Operational Infrastructure Support Program.
JournalFrontiers in Chemistry
Article NumberARTN 607769
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
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Science & TechnologyPhysical SciencesChemistry, MultidisciplinaryChemistry70S ribosomeAMPsantimicrobial peptidesDnaKhost defense peptidesPrAMPproline-rich antimicrobial peptideINDUCIBLE ANTIBACTERIAL PEPTIDESHEMIPTERAN INSECTIMMUNE-RESPONSELOCALIZATIONEXPRESSIONDROSOPHILAHEMOCYTESPROTEINSSUSCEPTIBILITYPURIFICATION