4.7 Article

Ribosome profiling reveals the fine-tuned response of Escherichia coli to mild and severe acid stress

Journal

MSYSTEMS
Volume -, Issue -, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/msystems.01037-23

Keywords

acid resistance; small proteins; transcription factor; ribosome profiling; RNA-Seq; machine learning

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This study compared the response of E.coli to different levels of acid stress using ribosome profiling and RNA sequencing. New genes and pathways were identified, and machine learning was utilized to distinguish the response to acid stress from general stress.
The ability to respond to acidic environments is crucial for neutralophilic bacteria. Escherichia coli has a well-characterized regulatory network that triggers a multitude of defense mechanisms to counteract excess protons. Nevertheless, systemic studies of the transcriptional and translational reprogramming of E. coli to different degrees of acid stress have not yet been performed. Here, we used ribosome profiling and RNA sequencing to compare the response of E. coli (pH 7.6) to sudden mild (pH 5.8) and severe near-lethal acid stress (pH 4.4) conditions that mimic passage through the gastrointestinal tract. We uncovered new differentially regulated genes and pathways, key transcriptional regulators, and 18 novel acid-induced candidate small open reading frames. By using machine learning and leveraging large compendia of publicly available E. coli expression data, we were able to distinguish between the response to acid stress and general stress. These results expand the acid resistance network and provide new insights into the fine-tuned response of E. coli to mild and severe acid stress.

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