Heterogeneity and Evolutionary Tunability of Escherichia coli Resistance against Extreme Acid Stress
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2022-12-21
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Journal Article
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Abstract
Since acidic environments often serve as an important line of defense against bacterial pathogens, it is important to fully understand how the latter manage to mount and evolve acid resistance mechanisms. Escherichia coli, a species harboring many pathovars, is typically equipped with the acid fitness island (AFI), a genomic region encoding the GadE master regulator together with several GadE-controlled functions to counter acid stress. This study reveals that gadE and consequently AFI functions are heterogeneously expressed even in the absence of any prior acid stress, thereby preemptively creating acid-resistant subpopulations within a clonal E. coli population. Directed evolution efforts selecting for modulated gadE expression confirm that a gain-of-function mutation in the EvgS sensor kinase can constitutively upregulate gadE expression and concomitant acid resistance. However, we reveal that such upregulation of EvgS also causes cross-resistance to heat stress because of SafA-mediated cross-activation of the PhoPQ regulon. Surprisingly, loss of function of the serC gene (encoding phosphoserine/phosphohydroxythreonine aminotransferase) can also significantly upregulate gadE expression, acid resistance, and heat cross-resistance, although via a currently cryptic mechanism. As such, our data reveal a noisy expression of gadE in E. coli that is functional for the survival of sudden acid stress and that can readily be genetically tuned.
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10 (6)
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American Society for Microbiology
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Subject
Escherichia coli; GadE; acid resistance; evolution; population heterogeneity