Increased Expression of Efflux Pump
            <i>norA</i>
            Drives the Rapid Evolutionary Trajectory from Tolerance to Resistance against Ciprofloxacin in Staphylococcus aureus

Yu, Xiaohui; Hao, Zehua; Liu, P L; Liu, M M; Zhao, L L; Zhao, Xin

doi:10.1128/aac.00594-22

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…As observed here, while CIP-E1 developed resistance to ciprofloxacin, it also showed increased sensitivity to gentamicin (Table S2). Many studies have explored efflux pump inhibitors as a possible strategy for postponing resistance development [47] or drugs targeting alternative sigma factors to reduce virulence [48]. There have been clinical trials for drugs targeting metabolic pathways that can reduce virulence and potentiate antibiotic activity against P. aeruginosa in cystic fibrosis patients [49].…”

Section: The Development Of Ciprofloxacin Resistance Is Multifactoria...mentioning

confidence: 99%

Adaptive response of Pseudomonas aeruginosa under serial ciprofloxacin exposure

Huynh,

Tran,

Pham

et al. 2024

Microbiology

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Graphical Abstract Sub-MICs of ciprofloxacin result in DNA breakage, triggering DNA damage stress and the SOS stress response. This, in turn, induces changes in regulatory factors and the translation machinery. Modifications to regulatory components, including MvaT, RpoS and RpoB, lead to the upregulation (depicted in green) of efflux pumps such as MexEF-OprN and the downregulation (depicted in red) of porins. Additionally, there are alterations in the expression of virulence factors. Concurrently, ciprofloxacin affects metabolic processes, shortens cell lengths and induces the formation of multinucleated filaments due to disruptions in cell replication.

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Section: The Development Of Ciprofloxacin Resistance Is Multifactoria...mentioning

confidence: 99%

Adaptive response of Pseudomonas aeruginosa under serial ciprofloxacin exposure

Huynh,

Tran,

Pham

et al. 2024

Microbiology

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“…Oleh karena itu, deteksi keberadaan Staphylococcus aureus di lingkungan sarana kesehatan sangat penting dilakukan dengan segera, karena potensi infeksi nosocomial, penyebaran infeksi, adanya strain yang resistensi antibiotik sebagai upaya dalam pengendalian infeksi (Willis et al, 2022;Yu et al, 2022). Dengan mengetahui keberadaan bakteri ini, langkah-langkah pencegahan dan pengendalian yang tepat dapat diambil, seperti meningkatkan kebersihan dan sanitasi, melaksanakan tindakan isolasi yang sesuai, dan memperkuat praktek kebersihan tangan (Howden et al, 2023;Khan et al, 2017;Nurlan et al, 2023;Tarigan et al, 2023).…”

Section: Pendahuluanunclassified

Pengembangan Protokol Deteksi Staphylococcus aureus Berbasis Molekuler

Koentjoro,

Alviani,

Jatmiko

et al. 2024

Bioscientist j. ilm. bosbiol.

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Staphylococcus aureus becomes a normal flora in humans, especially on the skin and in the nose. However, if it becomes excessive or if there are pathogenic variants, it can cause various health problems. The purpose of the study is to develop a molecular-based detection method for Staphylococcus aureus using the norA primer gene. The norA gene in Staphylococcus aureus is known to play a role in pathogenesis with its antibiotic resistance ability. This type of research is analytical observational with a cross-sectional method. The methods in the study include the isolation and identification of Staphylococcus aureus from healthcare facility equipment. Isolation and identification include bacterial isolation using Blood Agar Plate (BAP) media; isolate purification, Gram staining; biochemical tests using Mannitol Salt Agar (MSA) media, glucose tests, Voges Proskauer (VP) tests, catalase tests, and coagulase tests. Furthermore, S. aureus isolates were tested using a molecular-based method, namely Polymerase Chain Reaction (PCR). This method includes DNA isolation stages, qualitative testing with agarose gel electrophoresis, semi-quantitative testing with image J software, amplification with Real-Time Polymerase Chain Reaction (RT-PCR) using norA gene primers. The Mann-Whitney test results gave a value of p = 0.334 (p> 0.05) indicating the suitability between the culture method and the PCR method with the developed protocol in detecting Staphylococcus aureus. The developed method includes the use of base sequences in the norA gene primer, optimization of annealing and extension temperatures, and the concentration of DNA templates used.

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“…The need to address antimicrobial resistance mediated by NorA, one of the most studied EPs in Staphylococcus aureus [5][6][7], led to the identification of potent EPIs by exploitation of in silico drug repositioning approaches and medicinal chemistry campaigns [8][9][10]. We have been working for years on the design and synthesis of novel S. aureus NorA EPIs by comparing their biological activity on strains overexpressing norA or norA-deleted, resulting in the identification of several molecules able to fully restore the susceptibility to fluoroquinolone ciprofloxacin (CIP) of resistant S. aureus strains overexpressing NorA EP [8].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Staphylococcus pseudintermedius Efflux Pumps by Using Staphylococcus aureus NorA Efflux Pump Inhibitors

et al. 2023

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One promising approach in treating antibiotic-resistant bacteria is to “break” resistances connected with antibacterial efflux by co-administering efflux pump inhibitors (EPIs) with antibiotics. Here, ten compounds, previously optimized to restore the susceptibility to ciprofloxacin (CIP) of norA-overexpressing Staphylococcus aureus, were evaluated for their ability to inhibit norA-mediated efflux in Staphylococcus pseudintermedius and synergize with CIP, ethidium bromide (EtBr), gentamycin (GEN), and chlorhexidine digluconate (CHX). We focused efforts on S. pseudintermedius as a pathogenic bacterium of concern within veterinary and human medicine. By combining data from checkerboard assays and EtBr efflux inhibition experiments, the hits 2-arylquinoline 1, dihydropyridine 6, and 2-phenyl-4-carboxy-quinoline 8 were considered the best EPIs for S. pseudintermedius. Overall, most of the compounds, except for 2-arylquinoline compound 2, were able to fully restore the susceptibility of S. pseudintermedius to CIP and synergize with GEN as well, while the synergistic effect with CHX was less significant and often did not show a dose-dependent effect. These are valuable data for medicinal chemistry optimization of EPIs for S. pseudintermedius and lay the foundation for further studies on successful EPIs to treat staphylococcal infections.

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Increased Expression of Efflux Pump norA Drives the Rapid Evolutionary Trajectory from Tolerance to Resistance against Ciprofloxacin in Staphylococcus aureus

Cited by 5 publications

References 44 publications

Adaptive response of Pseudomonas aeruginosa under serial ciprofloxacin exposure

Adaptive response of Pseudomonas aeruginosa under serial ciprofloxacin exposure

Pengembangan Protokol Deteksi Staphylococcus aureus Berbasis Molekuler

Inhibition of Staphylococcus pseudintermedius Efflux Pumps by Using Staphylococcus aureus NorA Efflux Pump Inhibitors

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