Potent Chimeric Antimicrobial Derivatives of the Medicago truncatula NCR247 Symbiotic Peptide

Jenei, Sándor and Tiricz, Hilda and Szolomájer, János and Tímár, Edit and Klement, Éva and Lima, Rui Maria Dániel and Kata, Diána and Harmati, Mária and Buzás, Krisztina and Földesi, Imre and Tóth, Gábor and Endre, Gabriella and Kondorosi, Éva (2020) Potent Chimeric Antimicrobial Derivatives of the Medicago truncatula NCR247 Symbiotic Peptide. FRONTIERS IN MICROBIOLOGY, 11. ISSN 1664-302X

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In Rhizobium-legume symbiosis, the bacteria are converted into nitrogen-fixing bacteroids. In many legume species, differentiation of the endosymbiotic bacteria is irreversible, culminating in definitive loss of their cell division ability. This terminal differentiation is mediated by plant peptides produced in the symbiotic cells. In Medicago truncatula more than similar to 700 nodule-specific cysteine-rich (NCR) peptides are involved in this process. We have shown previously that NCR247 and NCR335 have strong antimicrobial activity on various pathogenic bacteria and identified interaction of NCR247 with many bacterial proteins, including FtsZ and several ribosomal proteins, which prevent bacterial cell division and protein synthesis. In this study we designed and synthetized various derivatives of NCR247, including shorter fragments and various chimeric derivatives. The antimicrobial activity of these peptides was tested on the ESKAPE bacteria; Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli as a member of Enterobacteriaceae and in addition Listeria monocytogenes and Salmonella enterica. The 12 amino acid long C-terminal half of NCR247, NCR247C partially retained the antimicrobial activity and preserved the multitarget interactions with partners of NCR247. Nevertheless NCR247C became ineffective on S. aureus, P. aeruginosa, and L. monocytogenes. The chimeric derivatives obtained by fusion of NCR247C with other peptide fragments and particularly with a truncated mastoparan sequence significantly increased bactericidal activity and altered the antimicrobial spectrum. The minimal bactericidal concentration of the most potent derivatives was 1.6 mu M, which is remarkably lower than that of most classical antibiotics. The killing activity of the NCR247-based chimeric peptides was practically instant. Importantly, these peptides had no hemolytic activity or cytotoxicity on human cells. The properties of these NCR derivatives make them promising antimicrobials for clinical use.

Item Type: Article
Additional Information: Funding Agency and Grant Number: Hungarian National Office for Research, Development and Innovation (NKFIH) [GINOP 2.3.2-15-2016-00014 Evomer, GINOP 2.3.2-15-2016-00015 I-KOM, GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00020]; ERCEuropean Research Council (ERC) [269067]; NKFIH Frontline Research project [KKP129924]; Balzan research grant; [TUDFO/47138-1/2019-ITM FIKP]; [20391-3/2018/FEKUSTRAT] Funding text: Research has been supported by the Hungarian National Office for Research, Development and Innovation (NKFIH) through the grants GINOP 2.3.2-15-2016-00014 Evomer and GINOP 2.3.2-15-2016-00015 I-KOM, GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00020; and by the ERC Advanced Grant 269067 "SymBiotics," the NKFIH Frontline Research project KKP129924 and the Balzan research grant to EKo; as well as by grants TUDFO/47138-1/2019-ITM FIKP and 20391-3/2018/FEKUSTRAT to GT.
Uncontrolled Keywords: DIFFERENTIATION; ANTIMICROBIAL PEPTIDES; CELL-CYCLE; plant symbiotic nodule-specific cysteine-rich peptides; NCR247; ESKAPE bacteria; modes of antimicrobial activity; killing kinetics; bacterial targets;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Q Science / természettudomány > QK Botany / növénytan
R Medicine / orvostudomány > RC Internal medicine / belgyógyászat
Depositing User: MTMT SWORD
Date Deposited: 24 Sep 2020 11:03
Last Modified: 24 Sep 2020 11:03

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