Coordinated regulation of acid resistance in Escherichia coli

作者：Patricia Aquino, Brent Honda, Suma Jaini, Anna Lyubetskaya, Krutika Hosur, Joanna G. Chiu, Iriny Ekladious, Dongjian Hu, Jin Lin, Marianna K. Sayeg, Arion I. Stettner, Julia Wang, Brandon G. Wong, Winnie S. Wong, Stephen Alexander, Cong Ba, Seth Bensussen, David B. Bernstein, Dana Braff, Susie Cha, Daniel Cheng, Jang Hwan Cho, Kenny F. Chou, James Chuang, Daniel Gastler, Daniel J. Grasso, John Greifenberger, Chen Guo, Anna Hawes, Divya V. Israni, Saloni R. Jain, Jessica Kim, Junyu Lei, Hao Li, David Li, Qian Li, Christopher P. Mancuso, Ning Mao, Salwa Masud, Cari L. Meisel, Jing Mi, Christine Nykyforchyn, Minhee Park, Hannah M. Peterson, Alfred K. Ramirez, Daniel S. Reynolds, Nae Gyune Rim, Jared Saffie, Hang Su, Wendell R. Su, Yaqing Su, Meng Sun, Meghan Thommes, Tao Tu, Nitinun Varongchayakul, Tyler E. Wagner, Benjamin H. Weinberg, Rouhui Yang, Anastasia Yaroslavsky, Christine J. Yoon, Yanyu Zhao, Alicia J. Zollinger, Anne M. Stringer, John W. Foster, Joseph T. Wade, Sahadaven Raman, Natasha Broude, Wilson W. Wong, James E. Galagan · 发表于：BMC Systems Biology · 年份：2017 · DOI：10.1186/s12918-016-0376-y · 被引用次数：149 · 研究领域：Bacterial Genetics and Biotechnology、Escherichia coli research studies、Microbial Metabolic Engineering and Bioproduction

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 o...