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Pseudomonas aeruginosa antitoxin HigA functions as a diverse regulatory factor by recognizing specific pseudopalindromic DNA motifs
Author(s) -
Song Yingjie,
Luo Guihua,
Zhu Yibo,
Li Tao,
Li Changcheng,
He Lihui,
Zhao Ninglin,
Zhao Chang,
Yang Jing,
Huang Qin,
Mu Xingyu,
Tang Xinyue,
Kang Mei,
Wu Siying,
He Yongxing,
Bao Rui
Publication year - 2021
Publication title -
environmental microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.954
H-Index - 188
eISSN - 1462-2920
pISSN - 1462-2912
DOI - 10.1111/1462-2920.15365
Subject(s) - antitoxin , biology , pseudomonas aeruginosa , gene , psychological repression , dna , genetics , repressor , microbiology and biotechnology , toxin , transcription factor , bacteria , gene expression
Summary Type II toxin‐antitoxin (TA) systems modulate many essential cellular processes in prokaryotic organisms. Recent studies indicate certain type II antitoxins also transcriptionally regulate other genes, besides neutralizing toxin activity. Herein, we investigated the diverse transcriptional repression properties of type II TA antitoxin PaHigA from Pseudomonas aeruginosa . Biochemical and functional analyses showed that PaHigA recognized variable pseudopalindromic DNA sequences and repressed expression of multiple genes. Furthermore, we presented high resolution structures of apo‐PaHigA, PaHigA‐P higBA and PaHigA‐P pa2440 complex, describing how the rearrangements of the HTH domain accounted for the different DNA‐binding patterns among HigA homologues. Moreover, we demonstrated that the N‐terminal loop motion of PaHigA was associated with its apo and DNA‐bound states, reflecting a switch mechanism regulating HigA antitoxin function. Collectively, this work extends our understanding of how the PaHigB/HigA system regulates multiple metabolic pathways to balance the growth and stress response in P. aeruginosa and could guide further development of anti‐TA oriented strategies for pathogen treatment.