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Identification and genetic dissection of convergent persister cell states
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Journal Article
Identification and genetic dissection of convergent persister cell states
2024
Overview
Persister cells, rare phenotypic variants that survive normally lethal levels of antibiotics, present a major barrier to clearing bacterial infections
1
. However, understanding the precise physiological state and genetic basis of persister formation has been a longstanding challenge. Here we generated a high-resolution single-cell
2
RNA atlas of
Escherichia coli
growth transitions, which revealed that persisters from diverse genetic and physiological models converge to transcriptional states that are distinct from standard growth phases and instead exhibit a dominant signature of translational deficiency. We then used ultra-dense CRISPR interference
3
to determine how every
E. coli
gene contributes to persister formation across genetic models. Among critical genes with large effects, we found
lon
, which encodes a highly conserved protease
4
, and
yqgE
, a poorly characterized gene whose product strongly modulates the duration of post-starvation dormancy and persistence. Our work reveals key physiologic and genetic factors that underlie starvation-triggered persistence, a critical step towards targeting persisters in recalcitrant bacterial infections.
Single-cell transcriptome analyses of growth phases in
Escherichia coli
identify a distinct transcriptional state occupied by antibiotic-tolerant persisters in which
lon
and
yqgE
have major roles.
Publisher
Nature Publishing Group UK
Subject
/ 38/23
/ Anti-Bacterial Agents - pharmacology
/ Clustered Regularly Interspaced Short Palindromic Repeats
/ Drug Resistance, Bacterial - genetics
/ Endodeoxyribonucleases - genetics
/ Endodeoxyribonucleases - metabolism
/ Escherichia coli - drug effects
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Gene Expression Regulation, Bacterial
/ Humanities and Social Sciences
/ Microbial Viability - drug effects
/ Microbial Viability - genetics
/ Protein Biosynthesis - genetics
/ RNA-Seq
/ Science
