Chimeric bacteriocin S5-PmnH engineered by domain swapping efficiently controls Pseudomonas aeruginosa infection in murine keratitis and lung models.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 04 2022
19 04 2022
Historique:
received:
13
01
2022
accepted:
22
03
2022
entrez:
20
4
2022
pubmed:
21
4
2022
medline:
22
4
2022
Statut:
epublish
Résumé
Rampant rise of multidrug resistant strains among Gram-negative bacteria has necessitated investigation of alternative antimicrobial agents with novel modes of action including antimicrobial proteins such as bacteriocins. The main hurdle in the clinical development of bacteriocin biologics is their narrow specificity and limited strain activity spectrum. Genome mining of bacteria for broadly active bacteriocins have identified a number of promising candidates but attempts to improve these natural multidomain proteins further, for example by combining domains of different origin, have so far met with limited success. We have found that domain swapping of Pseudomonas bacteriocins of porin type, when carried out between phylogenetically related molecules with similar mechanism of activity, allows the generation of highly active molecules with broader spectrum of activity, for example by abolishing strain resistance due to the presence of immunity proteins. The most broadly active chimera engineered in this study, S5-PmnH, exhibits excellent control of Pseudomonas aeruginosa infection in validated murine keratitis and lung infection models.
Identifiants
pubmed: 35440606
doi: 10.1038/s41598-022-09865-8
pii: 10.1038/s41598-022-09865-8
pmc: PMC9018753
doi:
Substances chimiques
Anti-Bacterial Agents
0
Anti-Infective Agents
0
Bacteriocins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5865Informations de copyright
© 2022. The Author(s).
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