Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i>
Tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> remains a predominant cause of mortality, especially in low- and middle-income nations. Recently, antimicrobial peptides have been discovered that at low concentrations could stimulate the growth of <i>M. tuberculosis<...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/12/1/177 |
| _version_ | 1797339647421972480 |
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| author | Kai Hilpert Tulika Munshi Paula M. López-Pérez Joana Sequeira-Garcia Tim J. Bull |
| author_facet | Kai Hilpert Tulika Munshi Paula M. López-Pérez Joana Sequeira-Garcia Tim J. Bull |
| author_sort | Kai Hilpert |
| collection | DOAJ |
| description | Tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> remains a predominant cause of mortality, especially in low- and middle-income nations. Recently, antimicrobial peptides have been discovered that at low concentrations could stimulate the growth of <i>M. tuberculosis</i> (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating <i>M. tuberculosis</i> growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH<sub>2</sub>-wkivfiwrr-CONH<sub>2</sub> significantly reduced the TTP by 25 h compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant <i>M. tuberculosis</i> strain. Additionally, for two peptides, a strongly diminished formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against <i>M. tuberculosis</i>. |
| first_indexed | 2024-03-08T09:50:15Z |
| format | Article |
| id | doaj.art-dc3309ee58374cf6b222a736ef8a70f5 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-08T09:50:15Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-dc3309ee58374cf6b222a736ef8a70f52024-01-29T14:06:48ZengMDPI AGMicroorganisms2076-26072024-01-0112117710.3390/microorganisms12010177Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i>Kai Hilpert0Tulika Munshi1Paula M. López-Pérez2Joana Sequeira-Garcia3Tim J. Bull4Institute of Infection and Immunity, St George’s, University of London, Cranmer Terrace, London SW17 0RE, UKInstitute of Infection and Immunity, St George’s, University of London, Cranmer Terrace, London SW17 0RE, UKTiKa Diagnostics Ltd., Cranmer Terrace, London SW17 0RE, UKTiKa Diagnostics Ltd., Cranmer Terrace, London SW17 0RE, UKInstitute of Infection and Immunity, St George’s, University of London, Cranmer Terrace, London SW17 0RE, UKTuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> remains a predominant cause of mortality, especially in low- and middle-income nations. Recently, antimicrobial peptides have been discovered that at low concentrations could stimulate the growth of <i>M. tuberculosis</i> (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating <i>M. tuberculosis</i> growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH<sub>2</sub>-wkivfiwrr-CONH<sub>2</sub> significantly reduced the TTP by 25 h compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant <i>M. tuberculosis</i> strain. Additionally, for two peptides, a strongly diminished formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against <i>M. tuberculosis</i>.https://www.mdpi.com/2076-2607/12/1/177antimicrobial peptide<i>Mycobacterium tuberculosis</i>diagnosisSpot synthesissubstitution analysisTB |
| spellingShingle | Kai Hilpert Tulika Munshi Paula M. López-Pérez Joana Sequeira-Garcia Tim J. Bull Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i> Microorganisms antimicrobial peptide <i>Mycobacterium tuberculosis</i> diagnosis Spot synthesis substitution analysis TB |
| title | Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i> |
| title_full | Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i> |
| title_fullStr | Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i> |
| title_full_unstemmed | Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i> |
| title_short | Redefining Peptide 14D: Substitutional Analysis for Accelerated TB Diagnosis and Enhanced Activity against <i>Mycobacterium tuberculosis</i> |
| title_sort | redefining peptide 14d substitutional analysis for accelerated tb diagnosis and enhanced activity against i mycobacterium tuberculosis i |
| topic | antimicrobial peptide <i>Mycobacterium tuberculosis</i> diagnosis Spot synthesis substitution analysis TB |
| url | https://www.mdpi.com/2076-2607/12/1/177 |
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