Tracking the progeny of bacterial persisters using a CRISPR-based genomic recorder.
Anti-Bacterial Agents
/ pharmacology
Genome, Bacterial
/ genetics
Plasmids
/ genetics
Clustered Regularly Interspaced Short Palindromic Repeats
/ genetics
CRISPR-Cas Systems
/ genetics
Salmonella typhimurium
/ genetics
Drug Resistance, Bacterial
/ genetics
Genomics
/ methods
Salmonella
/ genetics
Salmonella Infections
/ microbiology
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
medline:
7
10
2024
pubmed:
7
10
2024
entrez:
7
10
2024
Statut:
ppublish
Résumé
The rise of antimicrobial failure is a global emergency, and causes beyond typical genetic resistance must be determined. One probable factor is the existence of subpopulations of transiently growth-arrested bacteria, persisters, that endure antibiotic treatment despite genetic susceptibility to the drug. The presence of persisters in infected hosts has been successfully established, notably through the development of fluorescent reporters. It is proposed that infection relapse is caused by persisters resuming growth after cessation of the antibiotic treatment, but to date, there is no direct evidence for this. This is because no tool or reporter currently exists to track the extent to which infection relapse is initiated by regrowth of persisters in the host. Indeed, once they have transitioned out of the persister state, the progeny of persisters are genetically and phenotypically identical to susceptible bacteria in the population, making it virtually impossible to ascertain the source of relapse. We designed pSCRATCH (plasmid for Selective CRISPR Array expansion To Check Heritage), a molecular tool that functions to record the state of antibiotic persistence in the genome of
Identifiants
pubmed: 39374386
doi: 10.1073/pnas.2405983121
doi:
Substances chimiques
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2405983121Subventions
Organisme : HHS | NIH (NIH)
ID : AI168524
Organisme : Aramont Fund
ID : NA
Déclaration de conflit d'intérêts
Competing interests statement:The authors declare no competing interest.