Evidence of Cross-Regulation in Two Closely Related Pyruvate-Sensing Systems in Uropathogenic Escherichia coli

Steiner, Bradley D; Eberly, Allison R.; Hurst, Melanie N; Zhang, Ellisa W.; Green, Hamilton D.; Behr, Stefan; Jung, Kirsten; Hadjifrangiskou, Maria

doi:10.1007/s00232-018-0014-2

Cited by 14 publications

(18 citation statements)

References 51 publications

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“…Response regulators typically function as transcription factors that bind to bacterial DNA to alter transcriptional responses to intra- or extracellular stimuli [ 13 , 15 ]. Interestingly, some activated response regulators can cross-regulate transcription of genes associated with other two-component systems [ 16 , 17 ].…”

Section: Conserved Mechanisms Of Two-component Systems Apply To Qumentioning

confidence: 99%

Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

Butrico

Cassat

2020

Toxins

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Staphylococcus aureus is a Gram-positive pathogen capable of infecting nearly every vertebrate organ. Among these tissues, invasive infection of bone (osteomyelitis) is particularly common and induces high morbidity. Treatment of osteomyelitis is notoriously difficult and often requires debridement of diseased bone in conjunction with prolonged antibiotic treatment to resolve infection. During osteomyelitis, S. aureus forms characteristic multicellular microcolonies in distinct niches within bone. Virulence and metabolic responses within these multicellular microcolonies are coordinated, in part, by quorum sensing via the accessory gene regulator (agr) locus, which allows staphylococcal populations to produce toxins and adapt in response to bacterial density. During osteomyelitis, the Agr system significantly contributes to dysregulation of skeletal homeostasis and disease severity but may also paradoxically inhibit persistence in the host. Moreover, the Agr system is subject to complex crosstalk with other S. aureus regulatory systems, including SaeRS and SrrAB, which can significantly impact the progression of osteomyelitis. The objective of this review is to highlight Agr regulation, its implications on toxin production, factors that affect Agr activation, and the potential paradoxical influences of Agr regulation on disease progression during osteomyelitis.

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Section: Conserved Mechanisms Of Two-component Systems Apply To Qumentioning

confidence: 99%

Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

Butrico

Cassat

2020

Toxins

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“…Natural induction of yhjX has been previously reported by the Jung group to occur in E coli culture during mid-logarithmic growth phase (23), when bacterial cell density is high and nutrient depletion of LB begins to occur. We have previously shown that BtsS interacts with the non-cognate YpdB transcription factor to induce the upregulation of yhjX (23)(24)(25), a gene that is also induced under acidic conditions (26). In this work, we tested the hypothesis that L-serine deamination as a previously unrecognized acid resistance mechanism in E. coli.…”

Section: Introductionmentioning

confidence: 98%

Serine Deamination as a New Acid Resistance Mechanism in Escherichia coli

Wiebe¹,

Brannon

Steiner

et al. 2022

Preprint

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Escherichia coli associates with humans early in life and can occupy several body niches either as a commensal in the gut and vagina, or as a pathogen in the urinary tract. As such, E. coli has an arsenal of acid response mechanisms that allow it to withstand the different levels of acid stress encountered within and outside the host. Here, we report the discovery of an additional acid response mechanism that involves the deamination of L-serine to pyruvate by the conserved L-serine deaminases SdaA and SdaB. L-serine is the first amino acid to be imported in E. coli during growth in laboratory media, as the culture senesces. However, there remains a lack in knowledge as to why L-serine is preferred and how it is utilized. We show that in acidified media, L-serine is brought into the cell via the SdaC transporter and deletion of both SdaA and SdaB renders E. coli susceptible to acid stress, with a phenotype similar to other acid stress deletion mutants. We also show that the pyruvate produced by L-serine de-amination activates the pyruvate sensor BtsS, which in concert with the non-cognate response regulator YpdB upregulates the putative transporter YhjX, similar to what has been reported for this system during transition of E. coli to stationary phase. Based on these observations, we propose that L-serine deamination constitutes another acid response mechanism in E. colithat may function to protect E. coli as it transitions to stationary phase of growth.

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“…Pyruvate also plays essential roles in regulating bacterial survival and virulence, as pyruvate is a prominent nutrient in eukaryotic host environment [1][2][3][4][5][6]. In recent years, it has been shown that bacteria are able to sense external pyruvate and modulate gene expression accordingly [7,8].…”

Section: Introductionmentioning

confidence: 99%

Function and Regulation of the Pyruvate Transporter CstA in Escherichia coli

Gasperotti

Göing

Fajardo-Ruiz

et al. 2020

IJMS

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Pyruvate is a central metabolite that connects many metabolic pathways in living organisms. To meet the cellular pyruvate requirements, the enterobacterium Escherichia coli has at least three pyruvate uptake systems—the H+/pyruvate symporter BtsT, and two thus far less well-characterized transporters, YhjX and CstA. BtsT and CstA belong to the putative carbon starvation (CstA) family (transporter classification TC# 2.A.114). We have created an E. coli mutant that cannot grow on pyruvate as the sole carbon source and used it to characterize CstA as a pyruvate transporter. Transport studies in intact cells confirmed that CstA is a highly specific pyruvate transporter with moderate affinity and is energized by a proton gradient. When cells of a reporter strain were cultured in complex medium, cstA expression was maximal only in stationary phase. A DNA affinity-capture assay combined with mass spectrometry and an in-vivo reporter assay identified Fis as a repressor of cstA expression, in addition to the known activator cAMP-CRP. The functional characterization and regulation of this second pyruvate uptake system provides valuable information for understanding the complexity of pyruvate sensing and uptake in E. coli.

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Evidence of Cross-Regulation in Two Closely Related Pyruvate-Sensing Systems in Uropathogenic Escherichia coli

Cited by 14 publications

References 51 publications

Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

Serine Deamination as a New Acid Resistance Mechanism in Escherichia coli

Function and Regulation of the Pyruvate Transporter CstA in Escherichia coli

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