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9LTH

Crystal structure of transcriptional regulator (NrpR) from Streptococcus salivarius K12

Summary for 9LTH
Entry DOI10.2210/pdb9lth/pdb
DescriptorTranscriptional regulator (2 entities in total)
Functional Keywordsstreptococcus salivarius k12, transcriptional regulator, transcription
Biological sourceStreptococcus salivarius K12
Total number of polymer chains1
Total formula weight34091.27
Authors
Do, H.,Nguyen, D.l.,Kumaraswami, M. (deposition date: 2025-02-06, release date: 2025-05-21, Last modification date: 2025-07-09)
Primary citationNguyen, D.L.,Saha, S.,Thacharodi, A.,Singh, B.B.,Mitra, S.,Do, H.,Kumaraswami, M.
Environmental pH controls antimicrobial production by human probiotic Streptococcus salivarius.
J.Bacteriol., 207:e0005925-e0005925, 2025
Cited by
PubMed Abstract: K12 (SAL) is an oral probiotic used to treat or prevent oral infections caused by human pathogens. SAL produces at least three antimicrobials to exert its antimicrobial activity, namely, salivaricin A and salivaricin B, and the newly identified salivabactin. Salivabactin production is catalyzed by a polyketide/non-ribosomal peptide synthase hybrid biosynthetic gene cluster (BGC), termed as . The expression and salivabactin production are transient during SAL growth and , which may negatively impact SAL probiotic efficacy. To understand the molecular basis for transient expression, we assessed the impact of environmental pH on expression. We found that environmental acidification is a critical factor in promoting salivabactin antimicrobial activity and production by inducing expression. We further showed that acidic pH directly influences the quorum-sensing system that controls expression. During environmental acidification, SAL cytosol is acidified, which is sensed by a pH-sensitive histidine switch in the cytosolic transcription regulator, NrpR. The protonation of histidine during cytosolic acidification promotes high-affinity interactions between NrpR and its cognate intercellular signaling peptide, NIP, which leads to upregulation of expression. Collectively, our results indicate that SAL uses a sophisticated regulatory mechanism to orchestrate salivabactin production in an environment that is conducive to its antimicrobial activity.
PubMed: 40454994
DOI: 10.1128/jb.00059-25
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.59 Å)
Structure validation

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