Diclofenac mitigates virulence of multidrug-resistant Staphylococcus aureus
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ORIGINAL PAPER
Diclofenac mitigates virulence of multidrug‑resistant Staphylococcus aureus Hisham A. Abbas1 · Hamada Atallah1 · Mona A. El‑Sayed1 · Amira M. El‑Ganiny1 Received: 17 May 2020 / Revised: 17 July 2020 / Accepted: 21 July 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Staphylococcus aureus is an opportunistic pathogen that has the ability to cause a wide range of diseases including superficial infection and severe invasive life threatening infections. The pathogenicity of S. aureus is mediated by a group of virulence factors that mediate the colonization and penetration. The antibiotic resistance of S. aureus has evolved due to the abuse of antibiotics rendering the cure of infection very difficult especially with the shortage in new antibiotic production. To combat this shortage, repurposing of FDA-approved drugs against the virulence factors is a new strategy. The analgesic drug Diclofenac was found to have anti-virulence activity against Pseudomonas aeruginosa and Proteus mirabilis. This study aimed to demonstrate the anti-virulence effect of diclofenac against clinical MRSA isolates phenotypically and genotypically using qRT-PCR. In this study, diclofenac showed significant reduction in biofilm formation when compared to controls, the inhibition ranged between 22.67% and 70%. Also, remarkable inhibition of hemolysin activity was found (5.4–66.34%). Additionally, diclofenac has inhibitory activity against the staphyloxanthin production (8–57.2%). The results were confirmed by qRT-PCR that showed significant down-regulation of tested virulence genes. The down-regulation ranged from 43 to 64.05% for SarA, 36.85–64.75% for AgrA, 50–63.2% for hla, 38.55–60.35% for FnbA, 46.75–61.05% for IcaA, 27.55–64% for SigB and 51.05–72.8% for CrtM. In conclusion, diclofenac can be used in combination with antibiotics as anti-virulence agent against MDR-MRSA which will enhance the ability of immune system to eradicate infection. Keywords Staphylococcus aureus · Multidrug resistance · Virulence · Diclofenac sodium
Introduction Staphylococcus aureus (S. aureus) is a frequent pathogenic bacteria that can cause both community-acquired and hospital-acquired infection and prolong the hospital stay with high risk of morbidity and mortality (Gould et al. 2012; El Aila et al. 2017). Methicillin-resistant Staphylococcus aureus (MRSA) is also considered as normal flora colonizing onethird of the population globally especially in nose (Mimica et al. 2007). MRSA strains developed by acquisition of mecA gene involved in the mobile element staphylococcal cassette chromosome mec (SCCmec).
Communicated by Erko Stackebrandt. * Amira M. El‑Ganiny [email protected] 1
Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
MRSA can cause many infections that vary from skin and soft tissue infections to invasive infections including osteoarticular infection, bacteremia, meningitis, endocarditis, pneumonia and implanted devices associated infection
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