mexT

UniProt ID: Q9I0Z0
Organism: Pseudomonas aeruginosa PAO1
Review Status: COMPLETE
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Gene Description

MexT (PA2492, NfxC) is a LysR-type transcriptional activator of Pseudomonas aeruginosa. It binds nod-box-like sites in the mexEF-oprN promoter and activates the MexEF-OprN multidrug efflux pump, and directly activates a small regulon that includes mexS (qrh), whose product in turn modulates MexT. Full-length MexT is a homotetramer with an N-terminal winged-helix DNA-binding domain and a C-terminal regulatory domain with a putative ligand pocket. Through MexEF-OprN, which exports quinolone antibiotics and quorum-sensing quinolones, MexT affects antibiotic resistance, the quorum-sensing hierarchy and the production of virulence factors; with MexS it also represses the type III secretion system. mexT is frequently mutated in laboratory sublines and in clinical isolates.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000976 transcription cis-regulatory region binding
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN001248361, seeded by S. Typhimurium LeuO (CollecTF IPI) and this gene's own rows (expected self-appearance).
Reason: Consistent with direct promoter binding by MexT.
Supporting Evidence:
PMID:20727012
The mexT-proximal nod box was identified as the MexT-binding site by gel-shift assays using purified MexT.
GO:0000976 transcription cis-regulatory region binding
IDA
PMID:31722511
Crystal Structure of the Regulatory Domain of MexT, a Transc...
ACCEPT
Summary: DNase I footprinting of full-length MexT on the mexEF-oprN promoter.
Reason: Direct binding evidence; core.
Supporting Evidence:
PMID:31722511
A DNase I footprinting assay of full-length MexT identified two MexT-binding sequence in the mexEF oprN promoter.
GO:0000976 transcription cis-regulatory region binding
IMP
PMID:19846594
Transcriptome profiling defines a novel regulon modulated by...
ACCEPT
Summary: CollecTF row; motif mutagenesis and EMSA on the MexT regulon.
Reason: Core; consistent with the IDA row.
Supporting Evidence:
PMID:19846594
Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified.
GO:0000976 transcription cis-regulatory region binding
IMP
PMID:20727012
Transcriptional regulation of the mexEF-oprN multidrug efflu...
ACCEPT
Summary: CollecTF row; EMSA with purified MexT and promoter deletions.
Reason: Core; direct binding to the mexE promoter.
Supporting Evidence:
PMID:20727012
The mexT-proximal nod box was identified as the MexT-binding site by gel-shift assays using purified MexT.
GO:0001216 DNA-binding transcription activator activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN001248361, seeded by S. Typhimurium LeuO and MexT.
Reason: Core activity of MexT.
Supporting Evidence:
PMID:19846594
Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified.
GO:0001216 DNA-binding transcription activator activity
IMP
PMID:19846594
Transcriptome profiling defines a novel regulon modulated by...
ACCEPT
Summary: CollecTF row; MexT binds and activates its regulon promoters.
Reason: Core activity.
Supporting Evidence:
PMID:19846594
Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified.
GO:0001216 DNA-binding transcription activator activity
IMP
PMID:20727012
Transcriptional regulation of the mexEF-oprN multidrug efflu...
ACCEPT
Summary: CollecTF row; MexT binds the mexE promoter and is required for its expression.
Reason: Core activity.
Supporting Evidence:
PMID:20727012
The mexT-proximal nod box was identified as the MexT-binding site by gel-shift assays using purified MexT.
GO:0001216 DNA-binding transcription activator activity
IMP
PMID:39708318
Mutations in mexT bypass the stringent response dependency o...
ACCEPT
Summary: UniProt row; mexT mutant transcriptomics.
Reason: Consistent with the direct-binding rows.
Supporting Evidence:
PMID:39708318
However, MexT is an activator of mexEF-oprN expression
GO:0001217 DNA-binding transcription repressor activity
IMP
PMID:41128522
Modulation of the Pseudomonas aeruginosa quorum sensing casc...
MARK AS OVER ANNOTATED
Summary: UniProt row from the increased pqsE expression of the mexT deletion. The full text attributes this to MexEF-OprN (quinolone export), not to MexT binding the pqs promoter.
Reason: No direct DNA-binding repression is shown; the repression is downstream of MexT activating mexEF-oprN. Curators read the full text, so this is not removed, but it over-states MexT's own activity.
Supporting Evidence:
PMID:41128522
we hypothesized that constitutive MexT activity induces mexEF-oprN expression, leading to the repression of PQS QS, delayed pqsE expression, and delayed RhlR activation.
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000002
TOO GENERAL
Summary: InterPro2GO from the LysR HTH domain.
Reason: Entailed by the accepted GO:0001216 (is_a GO:0003700).
GO:0005667 transcription regulator complex
IDA
PMID:31722511
Crystal Structure of the Regulatory Domain of MexT, a Transc...
KEEP AS NON CORE
Summary: UniProt row; full-length MexT is a homotetramer by SEC-MALS.
Reason: True for a homotetrameric LysR regulator, but it records oligomerisation rather than a distinct complex.
Supporting Evidence:
PMID:31722511
FL MexT and MexT RD were homotetrameric and homodimeric in solution, respectively, as determined using SEC-MALS
GO:0006355 regulation of DNA-templated transcription
IBA
GO_REF:0000033
TOO GENERAL
Summary: IBA from PTN001248361, seeded by E. coli LeuO (IMP), S. Typhimurium LeuO (CollecTF) and this gene's PseudoCAP row. Sound at the node.
Reason: True, but entailed by the accepted GO:0045893.
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
TOO GENERAL
Summary: InterPro2GO from the LysR HTH domain.
Reason: Entailed by the accepted GO:0045893.
GO:0009372 quorum sensing
IMP
PMID:39708318
Mutations in mexT bypass the stringent response dependency o...
KEEP AS NON CORE
Summary: UniProt row. mexT mutants reactivate QS-dependent virulence; MexT shapes QS signalling mostly through MexEF-OprN export of quinolones.
Reason: A genuine but indirect, pump-mediated influence on QS.
Supporting Evidence:
PMID:41128522
we hypothesized that constitutive MexT activity induces mexEF-oprN expression, leading to the repression of PQS QS, delayed pqsE expression, and delayed RhlR activation.
GO:0010629 negative regulation of gene expression
IMP
PMID:9044268
Characterization of MexE-MexF-OprN, a positively regulated m...
KEEP AS NON CORE
Summary: UniProt row, probably for the coregulated decrease of the OprD porin in nfxC-type (MexT-active) strains.
Reason: Plausible indirect effect (UniProt calls the OprD down-regulation probable and post-transcriptional); not the core activity.
GO:0032993 protein-DNA complex
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: IBA from PTN001248361 recording the regulator-promoter complex.
Reason: True (EMSA complexes) but adds little beyond the cis-regulatory binding rows.
GO:0032993 protein-DNA complex
IMP
PMID:19846594
Transcriptome profiling defines a novel regulon modulated by...
KEEP AS NON CORE
Summary: CollecTF standard row.
Reason: True but adds little beyond GO:0000976.
GO:0032993 protein-DNA complex
IMP
PMID:20727012
Transcriptional regulation of the mexEF-oprN multidrug efflu...
KEEP AS NON CORE
Summary: CollecTF standard row.
Reason: True but adds little beyond GO:0000976.
GO:0045861 negative regulation of proteolysis
IMP
PMID:21075931
MexT regulates the type III secretion system through MexS an...
REMOVE
Summary: PseudoCAP row. The PAO1 mexT mutant produces more elastase; MexT is a transcription factor and does not act on protein hydrolysis.
Reason: Increased protease output in a regulator mutant is an indirect phenotype, not regulation of proteolysis. The transcriptional role is captured by the accepted regulation-of-transcription rows.
Supporting Evidence:
PMID:21075931
the mexS and mexT mutants of PAO1 shared the same phenotype of increased elastase and pyocyanin production compared to that in wild-type PAO1
GO:0045892 negative regulation of DNA-templated transcription
IMP
PMID:41128522
Modulation of the Pseudomonas aeruginosa quorum sensing casc...
KEEP AS NON CORE
Summary: UniProt row; pqsE and other genes rise in the mexT deletion, largely through MexEF-OprN.
Reason: True in the indirect sense; MexT's direct activity is activation.
Supporting Evidence:
PMID:41128522
we hypothesized that constitutive MexT activity induces mexEF-oprN expression, leading to the repression of PQS QS, delayed pqsE expression, and delayed RhlR activation.
GO:0045893 positive regulation of DNA-templated transcription
EXP
PMID:19846594
Transcriptome profiling defines a novel regulon modulated by...
ACCEPT
Summary: CollecTF row; MexT directly activates its regulon.
Reason: Core process.
Supporting Evidence:
PMID:19846594
Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified.
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:10515918
Characterization of MexT, the regulator of the MexE-MexF-Opr...
ACCEPT
Summary: PseudoCAP seed row for PTN001248361. Reporter fusions show MexT activates mexE and qrh transcription. Seed verdict SOUND.
Reason: Core process; later shown to be direct.
Supporting Evidence:
PMID:10515918
Expression of a qrh::lacZ fusion was also found to be activated by MexT.
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:39708318
Mutations in mexT bypass the stringent response dependency o...
ACCEPT
Summary: UniProt row from mexT mutant transcriptomics.
Reason: Consistent with the other rows.
Supporting Evidence:
PMID:39708318
However, MexT is an activator of mexEF-oprN expression
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:9044268
Characterization of MexE-MexF-OprN, a positively regulated m...
ACCEPT
Summary: UniProt row; the upstream LysR gene positively regulates mexEF-oprN.
Reason: Consistent with the other rows.
Supporting Evidence:
PMID:9044268
Expression of the mexEF-oprN operon was shown to be positively regulated by a protein encoded on a 1.5 kb DNA fragment located upstream of mexE
GO:0046677 response to antibiotic
IMP
PMID:39708318
Mutations in mexT bypass the stringent response dependency o...
MARK AS OVER ANNOTATED
Summary: UniProt row from altered aminoglycoside, colistin and ciprofloxacin susceptibility of mexT mutants.
Reason: Changed resistance in a regulator mutant is not a response to antibiotic; MexT is not shown to be triggered by the antibiotics.
Supporting Evidence:
PMID:39708318
leads to elevated aminoglycoside resistance
GO:0046677 response to antibiotic
IMP
PMID:9044268
Characterization of MexE-MexF-OprN, a positively regulated m...
MARK AS OVER ANNOTATED
Summary: UniProt row from the multidrug phenotype conferred by the regulator plasmid.
Reason: Resistance via pump expression, not a response to the antibiotic.
Supporting Evidence:
PMID:9044268
Expression of the mexEF-oprN operon was shown to be positively regulated by a protein encoded on a 1.5 kb DNA fragment located upstream of mexE
GO:0050709 negative regulation of protein secretion
IMP
PMID:21075931
MexT regulates the type III secretion system through MexS an...
KEEP AS NON CORE
Summary: PseudoCAP row. A PAO1 mexT mutant secretes much more ExoS; MexT represses the T3SS through MexS.
Reason: An indirect but genuine regulatory effect on T3SS-dependent secretion; peripheral to the core activator function.
Supporting Evidence:
PMID:21075931
However, a mexT mutant of PAO1 (PAO1 mexT ::Gm) resulted in much higher ExoS secretion than that of its parental strain PAO1
GO:1900377 negative regulation of secondary metabolite biosynthetic process
IMP
PMID:21075931
MexT regulates the type III secretion system through MexS an...
MODIFY
Summary: PseudoCAP row. The PAO1 mexT mutant makes more pyocyanin.
Reason: Correct but general; the secondary metabolite is pyocyanin, a phenazine. No negative regulation of pyocyanine biosynthesis term exists, so the specific supported term is GO:1900981. Non-core.
Supporting Evidence:
PMID:21075931
the mexS and mexT mutants of PAO1 shared the same phenotype of increased elastase and pyocyanin production compared to that in wild-type PAO1

Core Functions

LysR-type activator that binds nod-box-like sites and activates transcription of mexEF-oprN, mexS and a small directly regulated regulon.

Supporting Evidence:
  • PMID:20727012
    The mexT-proximal nod box was identified as the MexT-binding site by gel-shift assays using purified MexT.
  • PMID:19846594
    Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified.

References

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Suggested Questions for Experts

Q: What ligand binds the MexT regulatory-domain pocket, and does MexS act by producing or removing it?

πŸ“š Additional Documentation

Notes

(mexT-notes.md)

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