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Multiomics and single-cell sequencing reveal protein aggregation and translation fidelity enhance cross-tolerance of L. bulgaricus

ABSTRACT: Microorganisms enter dormancy under sublethal stress through the formation of protein aggregates, thereby acquiring cross-tolerance to environmental challenges. This phenomenon may be exploited to improve the survival ability of microbial products during the processing. In this context, this study involved inducing dormancy using sublethal concentrations of rifampicin to impart cross-tolerance to stress (acid, alkali, and heat) in L. bulgaricus. Suppressing bacterial transcriptional activity forced the bacteria into dormancy while inducing liquid-liquid phase separation (LLPS) -mediated protein aggregation. These aggregates were enriched in transcription/translation-related proteins and DNA repair enzymes, potentially serving as "molecular safe houses" that protected essential biomolecules and increased biochemical reaction efficiency through localised concentrations under stress. The formation of these protein aggregates was driven mainly by disordered proteins, and the expression of disordered proteins was probably regulated by the SOS response. The contribution of molecular chaperones and ion pumps to cross-tolerance were relatively small. Single-cell RNA sequencing revealed that the main resistance subgroups may enhance tolerance by ensuring translation fidelity through acylation and ribosome quality control, which was ambiguous in bulk RNA sequencing. This study advances the understanding of antibiotic-induced dormancy and cross-tolerance mechanisms, offering novel insights for developing engineering stress-resistant bacteria and combating pathogen resistance.

ORGANISM(S): Lactobacillus delbrueckii subsp. bulgaricus

PROVIDER: GSE304405 | GEO | 2026/03/23

REPOSITORIES: GEO

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