ArticleThe Journal of antimicrobial chemotherapy2015
Clinically relevant fluoroquinolone resistance due to constitutive overexpression of the PatAB ABC transporter in Streptococcus pneumoniae is conferred by disruption of a transcriptional attenuator.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Medicinal Plants: A Promising Therapeutic Approach for Addressing Antimicrobial Resistance.International journal of molecular sciences · 2026Review
- Article
- Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024Review
- ATP-binding cassette (ABC) transporters: structures and roles in bacterial pathogenesis.Journal of Zhejiang University. Science. B · 2024Review
- Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.ACS infectious diseases · 2024Review
- Convergent impact of vaccination and antibiotic pressures on pneumococcal populations.Cell chemical biology · 2024Review
- Antibiotic Potentiation Through Phytochemical-Based Efflux Pump Inhibitors to Combat Multidrug Resistance Bacteria.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- Advances in the Discovery of Efflux Pump Inhibitors as Novel Potentiators to Control Antimicrobial-Resistant Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps.Antibiotics (Basel, Switzerland) · 2023Review
- The culmination of multidrug-resistant efflux pumps vs. meager antibiotic arsenal era: Urgent need for an improved new generation of EPIs.Frontiers in microbiology · 2023Review
- Role of PatAB Transporter in Efflux of Levofloxacin inAntibiotics (Basel, Switzerland) · 2022Article
- What Approaches to Thwart Bacterial Efflux Pumps-Mediated Resistance?Antibiotics (Basel, Switzerland) · 2022Review
- Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae.The FEBS journal · 2022Article
- Role of the Two-Component System CiaRH in the Regulation of Efflux Pump SatAB and Its Correlation with Fluoroquinolone Susceptibility.Microbiology spectrum · 2022Article
- Bacterial Multidrug Efflux Pumps at the Frontline of Antimicrobial Resistance: An Overview.Antibiotics (Basel, Switzerland) · 2022Review
- Identification of Promoter Region Markers Associated With Altered Expression of Resistance-Nodulation-Division Antibiotic Efflux Pumps inFrontiers in microbiology · 2022Article
- Gain- and Loss-of-Function Screens Coupled to Next-Generation Sequencing for Antibiotic Mode of Action and Resistance Studies inAntimicrobial agents and chemotherapy · 2019Article
- Functionality of membrane proteins overexpressed and purified from E. coli is highly dependent upon the strain.Scientific reports · 2019Article
- Article
- Upregulation of the PatAB Transporter Confers Fluoroquinolone Resistance toFrontiers in microbiology · 2017Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesConstitutive overexpression of patAB has been observed in several unrelated fluoroquinolone-resistant laboratory mutants and clinical isolates; therefore, we sought to identify the cause of this overexpression.
methodsConstitutive patAB overexpression in two clinical isolates and a laboratory-selected mutant was investigated using a whole-genome transformation approach. To determine the effect of the detected terminator mutations, the WT and mutated patA leader sequences were cloned upstream of a GFP reporter. Finally, mutation of the opposing base in the stem-loop structure was carried out.
resultsWe identified three novel mutations causing up-regulation of patAB. All three of these were located in the upstream region of patA and affected the same Rho-independent transcriptional terminator structure. Each mutation was predicted to destabilize the terminator stem-loop to a different degree, and there was a strong correlation between predicted terminator stability and patAB expression level. Using a GFP reporter of patA transcription, these terminator mutations led to increased transcription of a downstream gene. For one mutant sequence, terminator stability could be restored by mutation of the opposing base in the stem-loop structure, demonstrating that transcriptional suppression of patAB is mediated by the terminator stem-loop structure.
conclusionsThis study showed that a mutation in a Rho-independent transcriptional terminator structure confers overexpression of patAB and fluoroquinolone resistance. Understanding how levels of the PatAB efflux pump are regulated increases our knowledge of pneumococcal biology and how the pneumococcus can respond to various stresses, including antimicrobials.
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