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Coordinated regulation of acid resistance in Escherichia coli.


ABSTRACT: BACKGROUND:Enteric Escherichia coli survives the highly acidic environment of the stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. The first described system, AR1, does not require an external amino acid. Its mechanism has not been determined. The regulation of the multiple AR systems and their coordination with broader cellular metabolism has not been fully explored. RESULTS:We utilized a combination of ChIP-Seq and gene expression analysis to experimentally map the regulatory interactions of four TFs: nac, ntrC, ompR, and csiR. Our data identified all previously in vivo confirmed direct interactions and revealed several others previously inferred from gene expression data. Our data demonstrate that nac and csiR directly modulate AR, and leads to a regulatory network model in which all four TFs participate in coordinating acid resistance, glutamate metabolism, and nitrogen metabolism. This model predicts a novel mechanism for AR1 by which the decarboxylation enzymes of AR2 are used with internally derived glutamate. This hypothesis makes several testable predictions that we confirmed experimentally. CONCLUSIONS:Our data suggest that the regulatory network underlying AR is complex and deeply interconnected with the regulation of GABA and glutamate metabolism, nitrogen metabolism. These connections underlie and experimentally validated model of AR1 in which the decarboxylation enzymes of AR2 are used with internally derived glutamate.

SUBMITTER: Aquino P 

PROVIDER: S-EPMC5217608 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Coordinated regulation of acid resistance in Escherichia coli.

Aquino Patricia P   Honda Brent B   Jaini Suma S   Lyubetskaya Anna A   Hosur Krutika K   Chiu Joanna G JG   Ekladious Iriny I   Hu Dongjian D   Jin Lin L   Sayeg Marianna K MK   Stettner Arion I AI   Wang Julia J   Wong Brandon G BG   Wong Winnie S WS   Alexander Stephen L SL   Ba Cong C   Bensussen Seth I SI   Bernstein David B DB   Braff Dana D   Cha Susie S   Cheng Daniel I DI   Cho Jang Hwan JH   Chou Kenny K   Chuang James J   Gastler Daniel E DE   Grasso Daniel J DJ   Greifenberger John S JS   Guo Chen C   Hawes Anna K AK   Israni Divya V DV   Jain Saloni R SR   Kim Jessica J   Lei Junyu J   Li Hao H   Li David D   Li Qian Q   Mancuso Christopher P CP   Mao Ning N   Masud Salwa F SF   Meisel Cari L CL   Mi Jing J   Nykyforchyn Christine S CS   Park Minhee M   Peterson Hannah M HM   Ramirez Alfred K AK   Reynolds Daniel S DS   Rim Nae Gyune NG   Saffie Jared C JC   Su Hang H   Su Wendell R WR   Su Yaqing Y   Sun Meng M   Thommes Meghan M MM   Tu Tao T   Varongchayakul Nitinun N   Wagner Tyler E TE   Weinberg Benjamin H BH   Yang Rouhui R   Yaroslavsky Anastasia A   Yoon Christine C   Zhao Yanyu Y   Zollinger Alicia J AJ   Stringer Anne M AM   Foster John W JW   Wade Joseph J   Raman Sahadaven S   Broude Natasha N   Wong Wilson W WW   Galagan James E JE  

BMC systems biology 20170106 1


<h4>Background</h4>Enteric Escherichia coli survives the highly acidic environment of the stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. The first described system, AR1, does not require an external amino acid. Its mechanism has not been determined. The regulation of the multiple AR systems and their coordination with broader cellular metabolism has not been full  ...[more]

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