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nfxB

negative regulator of MexCD-OprJ efflux pump

NCBI Pathogen Isolates

Bacterial genomes carrying this gene

NCBI Reference Gene Catalog

Known alleles and reference sequences

Protein entries specific to nfxB

Browse AMR rules for nfxB

Validation StatusSupported

Overview

Mechanism: mutations in nfxB lead to hyperexpression of MexCD-OprJ efflux pump
Validation Method: characterization of nfxB and mexD knockout mutants
Drug Classes: Azithromycin, Ciprofloxacin, Cefepime, Fluoroquinolone, Tetracycline, Kanamycin, Aminoglycoside, Levofloxacin, Chloramphenicol, Erythromycin, Tigecycline, QUINOLONE, Delafloxacin|Gepotidacin|Omadacycline, Tobramycin|Aztreonam, Ciprofloxacin|Levofloxacin|Amikacin|Aztreonam|Fosfomycin, Ceftazidime-avibactam|Ceftolozane/tazobactam, COLISTIN, Ciprofloxacin|Norfloxacin, Azithromycin|Ciprofloxacin|Cefepime, Aminoglycoside|Colistin
Organisms: Pseudomonas aeruginosa, Pseudomonas aeruginosa PAO1, Pseudomonas aeruginosa PA14, Pseudomonas aeruginosa clinical isolates, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii
Geographic Location: China|Other countries, India
Papers: 24
Databases: Reslit
Mutations: 36

Mutations

Protein Change	Nucleotide Change	Mechanism	Organism	Resistance To	Database	Validation Status
T39P	-	efflux pump transcriptional repressor NfxB	Pseudomonas aeruginosa	QUINOLONE	Reference Gene Catalog	Established
D56G	-	-	-	Ciprofloxacin	Reslit	Candidate
G133S	-	-	-	Ciprofloxacin	Reslit

Papers24

1

Azithromycin in Pseudomonas aeruginosa biofilms: bactericidal activity and selection of nfxB mutants.

PMID 19188376 · 2009

The study identified nfxB mutations as a key mechanism for azithromycin resistance in Pseudomonas aeruginosa biofilms, leading to hyperexpression of the MexCD-OprJ efflux pump and cross-resistance to ciprofloxacin and cefepime.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: negative regulator of MexCD-OprJ efflux pump
Source Database: Reslit
Mechanism: mutations in nfxB lead to hyperexpression of MexCD-OprJ efflux pump
Confers Resistance To: AzithromycinCiprofloxacinCefepime
Organisms Tested In: • Pseudomonas aeruginosa
Validation Method: characterization of nfxB and mexD knockout mutants

2

Mechanisms decreasing in vitro susceptibility to the LpxC inhibitor CHIR-090 in the gram-negative pathogen Pseudomonas aeruginosa.

PMID 22024823 · 2012

The study identifies several mechanisms by which Pseudomonas aeruginosa can reduce susceptibility to the LpxC inhibitor CHIR-090, including mutations in efflux pump regulators (mexR, nfxB, mexS), overexpression of LpxC, and mutations in the fatty acid biosynthesis gene fabG.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: transcriptional repressor of MexCD-OprJ efflux pump
Source Database: Reslit
Organisms Tested In: • Pseudomonas aeruginosa
Validation Method: mutant generation and MIC testing

3

Genomics of adaptation during experimental evolution of the opportunistic pathogen Pseudomonas aeruginosa.

PMID 23028345 · 2012

The study identifies several chromosomal mutations in P. aeruginosa that confer resistance to ciprofloxacin and adaptation to a CF-like environment, including mutations in gyrA, gyrB, nfxB, orfN, morA, wspF, and Pa14_56280.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: transcriptional repressor
Source Database: Reslit
Confers Resistance To: Fluoroquinolone
Organisms Tested In: • Pseudomonas aeruginosa
Validation Method: whole-genome sequencing and MIC testing
Sequence Accession: NC_008463.1

4

Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa.

PMID 25034696 · 2014

VqsM directly binds to the promoter regions of exsA and nfxB, regulating their expression and contributing to antibiotic resistance in Pseudomonas aeruginosa.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: regulator
Source Database: Reslit
Mechanism: directly binds to the promoter region and regulates expression
Confers Resistance To: TetracyclineKanamycin
Organisms Tested In: • Pseudomonas aeruginosa
Validation Method: EMSAs and promoter-lux fusion assays

5

Evolution of Cost-Free Resistance under Fluctuating Drug Selection in Pseudomonas aeruginosa.

PMID 28744479 · 2017

The study identifies mutations in nfxB, gyrA, and gyrB as key drivers of ciprofloxacin resistance in Pseudomonas aeruginosa under fluctuating drug selection, demonstrating that second-site mutations contribute to cost-free resistance.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: efflux pump regulator
Source Database: Reslit
Mechanism: mutations in the nfxB efflux pump regulator increase resistance
Confers Resistance To: Ciprofloxacin
Organisms Tested In: • Pseudomonas aeruginosa
Validation Method: whole-genome sequencing and allelic exchange

6

History of antibiotic adaptation influences microbial evolutionary dynamics during subsequent treatment.

PMID 28792497 · 2017

The study identifies various mutations in Pseudomonas aeruginosa that contribute to resistance against piperacillin, tobramycin, and ciprofloxacin, highlighting the impact of historical antibiotic exposure on subsequent resistance development.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: transcriptional repressor that regulates MexCD-OprJ
Source Database: Reslit
Mechanism: inactivation leads to up-regulation of MexCD-OprJ and increased ciprofloxacin resistance
Confers Resistance To: Ciprofloxacin
Organisms Tested In: • Pseudomonas aeruginosa
Validation Method: genomic mutations and experimental validation
Sequence Accession: NCBI BioProject PRJNA375123|NCBI:PRJNA567890

7

Application of six multiplex PCR's among 200 clinical isolates of Pseudomonas aeruginosa for the detection of 20 drug resistance encoding genes.

PMID 29413231 · 2018

The study identified several beta-lactamase genes (blaTem, blaOXA, blaCTX-M-15, blaVim, blaGes, blaVeb, blaDIM, AmpC) and efflux pump genes (MexA, MexB, OprM, MexC, MexD, OprJ, MexX, MexY, OprN, nfxB, MexR, OprD) in Pseudomonas aeruginosa clinical isolates, highlighting their roles in mediating resistance to various antibiotics.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: Regulator of efflux pump
Source Database: Reslit
Confers Resistance To: FluoroquinoloneAminoglycoside
Organisms Tested In: • Pseudomonas aeruginosa
Geographic Location: India
Validation Method: multiplex PCR

8

A Large-Scale Whole-Genome Comparison Shows that Experimental Evolution in Response to Antibiotics Predicts Changes in Naturally Evolved Clinical Pseudomonas aeruginosa.

PMID 31570397 · 2019

The study identifies multiple genes and mutations associated with antibiotic resistance in Pseudomonas aeruginosa through experimental evolution and whole-genome sequencing, highlighting the clinical relevance of these findings.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: efflux pump regulator
Source Database: Reslit
Confers Resistance To: Ciprofloxacin
Organisms Tested In: • Pseudomonas aeruginosa PAO1
Validation Method: whole-genome sequencing and experimental evolution
Sequence Accession: PRJNA542028

9

Low Ciprofloxacin Concentrations Select Multidrug-Resistant Mutants Overproducing Efflux Pumps in Clinical Isolates of Pseudomonas aeruginosa.

PMID 36000896 · 2022

Low ciprofloxacin concentrations select for multidrug-resistant mutants in Pseudomonas aeruginosa clinical isolates, primarily through overproduction of efflux pumps mexCD-oprJ and mexEF-oprN, along with mutations in gyrA, parE, mexS, and nfxB.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: efflux pump regulator
Source Database: Reslit
Mechanism: overexpression of MexCD-OprJ and MexEF-OprN efflux pumps
Confers Resistance To: CiprofloxacinLevofloxacinChloramphenicolErythromycinTetracyclineTigecycline
Organisms Tested In: • Pseudomonas aeruginosa PA14
• Pseudomonas aeruginosa clinical isolates
Validation Method: sequencing of genes and expression analysis

10

Promoter regulatory mode evolution enhances the high multidrug resistance of tmexCD1-toprJ1.

PMID 38564664 · 2024

The study identifies the tmexCD1-toprJ1 efflux pump gene cluster and its regulatory elements, showing that variations in the TNfxB and NfxB regulators and promoter regions contribute to multidrug resistance. Key mutations, such as T39R in TNfxB1, TNfxB3, and NfxB, weaken repressor function, enhancing efflux pump expression and resistance.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: local regulator
Source Database: Reslit
Organisms Tested In: • Escherichia coli
• Pseudomonas aeruginosa
Geographic Location: China|Other countries
Validation Method: antibiotics susceptibility testing, RT-qPCR, β-galactosidase assay

11

Targeting efflux pumps prevents the multi-step evolution of high-level resistance to fluoroquinolone in Pseudomonas aeruginosa.

PMID 39982069 · 2025

The study identifies mutations in nfxB, gyrA, and gyrB as contributing to high-level fluoroquinolone resistance in Pseudomonas aeruginosa, with nfxB mutations playing a key role in antibiotic tolerance.

Gene Information

Gene Name: nfxB
Allele: nfxB
Encodes: negative regulator of efflux pumps
Source Database: Reslit
Confers Resistance To: Fluoroquinolone
Organisms Tested In: • Pseudomonas aeruginosa
Validation Method: whole-genome sequencing and MIC testing
Sequence Accession: PRJNA998700|PXD044054