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Novel antimicrobial peptides identified in legume plant, Medicago truncatula
One of the major issues in healthcare today is antibiotic resistance. Antimicrobial peptides (AMPs), a subclass of host defense peptides, have been suggested as a viable solution for the multidrug resistance problem. Legume plants express more than 700 nodule-specific cysteine-rich (NCR) peptides. T...
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Published in: | Microbiology spectrum 2024-02, Vol.12 (2), p.e0182723-e0182723 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | One of the major issues in healthcare today is antibiotic resistance. Antimicrobial peptides (AMPs), a subclass of host defense peptides, have been suggested as a viable solution for the multidrug resistance problem. Legume plants express more than 700 nodule-specific cysteine-rich (NCR) peptides. Three NCR peptides (NCR094, NCR888, and NCR992) were predicted to have antimicrobial activity using
AMP prediction programs. This study focused on investigating the roles of the NCRs in antimicrobial activity and antibiofilm activity, followed by
toxicity profiling. Different variants were synthesized, i.e., mutated and truncated derivatives. The effect on the growth of
and methicillin-resistant
(MRSA) was monitored post-treatment, and survived cells were counted using an
and
killing assay. The antibiofilm assay was conducted using subinhibitory concentrations of the NCRs and monitoring
biomass, followed by crystal violet staining. The cytotoxicity profile was evaluated using erythrocyte hemolysis and leukemia (K562) cell line toxicity assays. Out of the NCRs, NCR094 and NCR992 displayed mainly
and
bactericidal activity on
. NCR094 wild type (WT) and NCR992 eradicated
at different potency; NCR094 and NCR992 killed
completely at 25 and 50 µM, respectively. However, both peptides in the wild type showed negligible bactericidal effect on MRSA
and
. NCR094 and its derivatives relatively retained the antimicrobial activity on
and
. NCR992 WT lost its antimicrobial activity on
, yet the different truncated and mutated variants retained some of the antimicrobial role
. All the different variants of NCR094 had no effect on MRSA
and
. Similarly, NCR992's variants had a negligible bactericidal role on MRSA
, yet the truncated variants had a significantly high bactericidal effect on MRSA
. NCR094.3 (cystine replacement variant) and NCR992.1 displayed significant antibiofilm activity more than 90%. NCR992.3 and NCR992.2 displayed more than 50% of antibiofilm activity. All the NCR094 forms had no toxicity, except NCR094.1 (49.38%, SD ± 3.46) and all NCR992 forms (63%-93%), which were above the cutoff (20%). Only NCR992.2 showed low toxicity on K562 (24.8%, SD ± 3.40), yet above the 20% cutoff. This study provided preliminary antimicrobial and safety data for the potential use of these peptides for therapeutical applications.IMPORTANCEThe discovery of new antibiotics is urgently needed, given the global expansion of antibiotic-resistant bacteria and the rising mortality rate. |
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ISSN: | 2165-0497 2165-0497 |
DOI: | 10.1128/spectrum.01827-23 |