ArticleBMC microbiology2015
Impact of efflux in the development of multidrug resistance phenotypes in Staphylococcus aureus.
Article in BMC microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
- Designing Antibiotics with Inherent Resistance to Efflux as a Strategy to Revive Discovery against Multidrug-Resistant Pathogens.Journal of medicinal chemistry · 2026Article
- Antimicrobial Resistance inAntibiotics (Basel, Switzerland) · 2026Review
- Discovery of Coerumycin, a Cinnamycin-like Lantibiotic fromAntibiotics (Basel, Switzerland) · 2026Article
- Occurrence, variability and evolutionary relations of efflux pump determinants across five pathogenicFrontiers in pharmacology · 2026Article
- Drug Repurposing: An Emerging Strategy inJournal of microbiology and biotechnology · 2025Review
- Reprogramming resistance: phage-antibiotic synergy targets efflux systems in ESKAPEE pathogens.mBio · 2025Review
- A Mechanistic Insight into the Anti-Staphylococcal Mode of Action of (+)-Usnic Acid and Its Synergy with Norfloxacin Against Methicillin-ResistantBiomolecules · 2025Article
- Evaluation of Amlodipine and Imipramine Efficacy to TreatAntibiotics (Basel, Switzerland) · 2025Article
- Influence of antibiotic resistance on disinfectant tolerance of Escherichia coli, Staphylococcus aureus, Enterococcus faecium and Campylobacter jejuni.Access microbiology · 2025Article
- Plant-Derived Antimicrobials and Their Crucial Role in Combating Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2024Review
- Exploring Efflux as a Mechanism of Reduced Susceptibility towards Biocides and Fluoroquinolones inAnimals : an open access journal from MDPI · 2023Article
- Recent Trends of Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2023Article
- Genomic alterations involved in fluoroquinolone resistance development in Staphylococcus aureus.PloS one · 2023Article
- Occurrence and Variability of the Efflux Pump GeneInternational journal of molecular sciences · 2022Article
- Identification of Mobile Colistin Resistance GeneAntibiotics (Basel, Switzerland) · 2022Article
- Synergistic Role of Plant Extracts and Essential Oils against Multidrug Resistance and Gram-Negative Bacterial Strains Producing Extended-Spectrum β-Lactamases.Antibiotics (Basel, Switzerland) · 2022Review
- Mutations in SilS and CusS/OmpC represent different routes to achieve high level silver ion tolerance in Klebsiella pneumoniae.BMC microbiology · 2022Article
- Long-Term Exposure to Octenidine in a Simulated Sink Trap Environment Results in Selection of Pseudomonas aeruginosa,Applied and environmental microbiology · 2021Article
- Whole Genome Sequencing of Staphylococci Isolated From Bovine Milk Samples.Frontiers in microbiology · 2021Article
- Design and Characterisation of Inhibitory Peptides against Bleg1_2478, an Evolutionary Divergent B3 Metallo-β-lactamase.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEfflux has been recognized as a resistance mechanism to antimicrobials in Staphylococcus aureus; however its role on the development of clinically relevant resistance is still poorly characterized. This study aimed to examine the impact of efflux on development of resistance to fluoroquinolones and other antimicrobials in S. aureus strains representing relevant phenotypes in terms of antibiotic susceptibility and efflux activity.
methodsTwo closely related methicillin- and ciprofloxacin-resistant Staphylococcus aureus clinical strains, with different efflux capacity and the pan-susceptible strain ATCC25923 were exposed to constant concentrations of the efflux pump (EP) substrates ciprofloxacin, ethidium bromide and cetrimide. Parental and exposed strains were tested regarding their susceptibility towards antibiotics, biocides and ethidium bromide, efflux capacity and levels of EP gene expression. Occurrence of resistance-associated mutations was screened by sequencing.
resultsMultidrug resistance phenotypes emerged upon exposure, independently of the substrate or its concentration, which were correlated with increased efflux capacity of the exposed strains. The temporal pattern of EP gene expression disclosed an early-response with high expression of several genes, followed by a late-response, characterized by overexpression of specific genes. The overall cell response was more pronounced for strains with an initial basal efflux activity. Remarkably, detection of the IS256 element in the promoter regions of mgrA and norA, in some cases associated with increased gene expression, suggests that these genes may be hot spots for IS256 insertion events. The results obtained with exposure of ATCC25923 to ciprofloxacin were particularly striking, revealing a step-wise development of fluoroquinolone resistance, with a first efflux-mediated response, followed by the occurrence of a mutation in grlA that resulted in phenotypic resistance. Additionally, challenge by non-fluoroquinolone agents, particularly cetrimide, promoted cross resistance to fluoroquinolones, revealing the potential role of biocides as selective pressure for the emergence of resistance to these antibiotics.
conclusionsThis study reveals efflux as a significant component of S. aureus resistance to fluoroquinolones and biocides and as a primary mechanism to withstand stress imposed by antimicrobials. This efflux-mediated response can result in the emergence of multidrug resistance in healthcare environments and should be taken into account in the management of this major pathogen.
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