Role of GlnR in acid-mediated repression of genes encoding proteins involved in glutamine and glutamate metabolism in streptococcus Mutans

Pei Min Chen, Yi Ywan M. Chen, Sung Liang Yu, Singh Sher, Chern Hsiung Lai, Jean San Chia*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

25 Scopus citations

Abstract

The acid tolerance response (ATR) is one of the major virulence traits of Streptococcus mutans. In this study, the role of GlnR in acid-mediated gene repression that affects the adaptive ATR in S. mutans was investigated. Using a whole-genome microarray and in silico analyses, we demonstrated that GlnR and the GlnR box (ATGTNAN7TNACAT) were involved in the transcriptional repression of clusters of genes encoding proteins involved in glutamine and glutamate metabolism under acidic challenge. Reverse transcription-PCR (RT-PCR) analysis revealed that the coordinated regulation of the GlnR regulon occurred 5 min after acid treatment and that prolonged acid exposure (30 min) resulted in further reduction in expression. A lower level but consistent reduction in response to acidic pH was also observed in chemostat-grown cells, confirming the negative regulation of GlnR. The repression by GlnR through the GlnR box in response to acidic pH was further confirmed in the citBZC operon, containing genes encoding the first three enzymes in the glutamine/glutamate biosynthesis pathway. The survival rate of the GlnRdeficient mutant at pH 2.8 was more than 10-fold lower than that in the wild-type strain 45 min after acid treatment, suggesting that the GlnR regulon participates in S. mutans ATR. It is hypothesized that downregulation of the synthesis of the amino acid precursors in response to acid challenge would promote citrate metabolism to pyruvate, with the consumption of H+ and potential ATP synthesis. Such regulation will ensure an optimal acid adaption in S. mutans.

Original languageEnglish
Pages (from-to)2478-2486
Number of pages9
JournalApplied and Environmental Microbiology
Volume76
Issue number8
DOIs
StatePublished - 04 2010

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