Publication

Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp.

Cebrian, R., Macia-Valero, A., Jati, A. P. & Kuipers, O. P., 24-Sep-2019, In : Frontiers in Microbiology. 10, 17 p., 2154.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Cebrian, R., Macia-Valero, A., Jati, A. P., & Kuipers, O. P. (2019). Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp. Frontiers in Microbiology, 10, [2154]. https://doi.org/10.3389/fmicb.2019.02154

Author

Cebrian, Ruben ; Macia-Valero, Alicia ; Jati, Afif P. ; Kuipers, Oscar P. / Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp. In: Frontiers in Microbiology. 2019 ; Vol. 10.

Harvard

Cebrian, R, Macia-Valero, A, Jati, AP & Kuipers, OP 2019, 'Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp.', Frontiers in Microbiology, vol. 10, 2154. https://doi.org/10.3389/fmicb.2019.02154

Standard

Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp. / Cebrian, Ruben; Macia-Valero, Alicia; Jati, Afif P.; Kuipers, Oscar P.

In: Frontiers in Microbiology, Vol. 10, 2154, 24.09.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Cebrian R, Macia-Valero A, Jati AP, Kuipers OP. Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp. Frontiers in Microbiology. 2019 Sep 24;10. 2154. https://doi.org/10.3389/fmicb.2019.02154


BibTeX

@article{686e9f05e2c24b26bc89ac81c45eee77,
title = "Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp.",
abstract = "Clostridium difficile has been reported as the most common cause of nosocomial diarrhea (antibiotic-associated diarrhea), resulting in significant morbidity and mortality in hospitalized patients. The resistance of the clostridia' spores to antibiotics and their side effects on the gut microbiota are two factors related to the emergence of infection and its relapses. Lantibiotics provide an innovative alternative for cell growth inhibition due to their dual mechanism of action (membrane pore-forming and cell wall synthesis inhibition) and low resistance rate. Based on the fact that bacteriocins are usually active against bacteria closely related to the producer strains, a new dual approach combining genome mining and synthetic biology was performed, by designing new lantibiotics with high activity and specificity toward Clostridium. We first attempted the heterologous expression of putative lantibiotics identified following Clostridium genome mining. Subsequently, we designed new hybrid lantibiotics combining the start or end of the putative clostridial peptides and the start or end parts of nisin. The designed peptides were cloned and expressed using the nisin biosynthetic machinery in Lactococcus lactis. From the 20 initial peptides, only 1 fulfilled the requirements established in this work to be considered as a good candidate: high heterologous production level and high specificity/activity against clostridial species. The high specificity and activity observed for the peptide AMV10 makes it an interesting candidate as an alternative to traditional antibiotics in the treatment of C. difficile infections, avoiding side effects and protecting the normal gut microbiota.",
keywords = "genome mining, Clostridium difficile, antimicrobial susceptibility, lantibiotic design, nisin, COMPLETE GENOME SEQUENCE, LACTIC-ACID BACTERIA, DIFFICILE INFECTION, LACTOCOCCUS-LACTIS, NISIN, BIOSYNTHESIS, PEPTIDES, TARGET, GENE, TRANSFORMATION",
author = "Ruben Cebrian and Alicia Macia-Valero and Jati, {Afif P.} and Kuipers, {Oscar P.}",
year = "2019",
month = "9",
day = "24",
doi = "10.3389/fmicb.2019.02154",
language = "English",
volume = "10",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Design and Expression of Specific Hybrid Lantibiotics Active Against Pathogenic Clostridium spp.

AU - Cebrian, Ruben

AU - Macia-Valero, Alicia

AU - Jati, Afif P.

AU - Kuipers, Oscar P.

PY - 2019/9/24

Y1 - 2019/9/24

N2 - Clostridium difficile has been reported as the most common cause of nosocomial diarrhea (antibiotic-associated diarrhea), resulting in significant morbidity and mortality in hospitalized patients. The resistance of the clostridia' spores to antibiotics and their side effects on the gut microbiota are two factors related to the emergence of infection and its relapses. Lantibiotics provide an innovative alternative for cell growth inhibition due to their dual mechanism of action (membrane pore-forming and cell wall synthesis inhibition) and low resistance rate. Based on the fact that bacteriocins are usually active against bacteria closely related to the producer strains, a new dual approach combining genome mining and synthetic biology was performed, by designing new lantibiotics with high activity and specificity toward Clostridium. We first attempted the heterologous expression of putative lantibiotics identified following Clostridium genome mining. Subsequently, we designed new hybrid lantibiotics combining the start or end of the putative clostridial peptides and the start or end parts of nisin. The designed peptides were cloned and expressed using the nisin biosynthetic machinery in Lactococcus lactis. From the 20 initial peptides, only 1 fulfilled the requirements established in this work to be considered as a good candidate: high heterologous production level and high specificity/activity against clostridial species. The high specificity and activity observed for the peptide AMV10 makes it an interesting candidate as an alternative to traditional antibiotics in the treatment of C. difficile infections, avoiding side effects and protecting the normal gut microbiota.

AB - Clostridium difficile has been reported as the most common cause of nosocomial diarrhea (antibiotic-associated diarrhea), resulting in significant morbidity and mortality in hospitalized patients. The resistance of the clostridia' spores to antibiotics and their side effects on the gut microbiota are two factors related to the emergence of infection and its relapses. Lantibiotics provide an innovative alternative for cell growth inhibition due to their dual mechanism of action (membrane pore-forming and cell wall synthesis inhibition) and low resistance rate. Based on the fact that bacteriocins are usually active against bacteria closely related to the producer strains, a new dual approach combining genome mining and synthetic biology was performed, by designing new lantibiotics with high activity and specificity toward Clostridium. We first attempted the heterologous expression of putative lantibiotics identified following Clostridium genome mining. Subsequently, we designed new hybrid lantibiotics combining the start or end of the putative clostridial peptides and the start or end parts of nisin. The designed peptides were cloned and expressed using the nisin biosynthetic machinery in Lactococcus lactis. From the 20 initial peptides, only 1 fulfilled the requirements established in this work to be considered as a good candidate: high heterologous production level and high specificity/activity against clostridial species. The high specificity and activity observed for the peptide AMV10 makes it an interesting candidate as an alternative to traditional antibiotics in the treatment of C. difficile infections, avoiding side effects and protecting the normal gut microbiota.

KW - genome mining

KW - Clostridium difficile

KW - antimicrobial susceptibility

KW - lantibiotic design

KW - nisin

KW - COMPLETE GENOME SEQUENCE

KW - LACTIC-ACID BACTERIA

KW - DIFFICILE INFECTION

KW - LACTOCOCCUS-LACTIS

KW - NISIN

KW - BIOSYNTHESIS

KW - PEPTIDES

KW - TARGET

KW - GENE

KW - TRANSFORMATION

U2 - 10.3389/fmicb.2019.02154

DO - 10.3389/fmicb.2019.02154

M3 - Article

VL - 10

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

M1 - 2154

ER -

ID: 98625343