Tracking the progeny of bacterial persisters using a CRISPR-based genomic recorder.


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
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

e2405983121

Subventions

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.

Auteurs

Julian Anthony Rycroft (JA)

Department of Microbiology, Harvard Medical School, Boston, MA 02115.

Rachel Teresa Giorgio (RT)

Department of Microbiology, Harvard Medical School, Boston, MA 02115.

Molly Sargen (M)

Department of Microbiology, Harvard Medical School, Boston, MA 02115.

Sophie Helaine (S)

Department of Microbiology, Harvard Medical School, Boston, MA 02115.

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Classifications MeSH