Inhibition of Bacterial Multidrug Resistance by Celecoxib, a Cyclooxygenase-2 Inhibitor

Kalle, Arunasree M.; Rizvi, Arshad

doi:10.1128/aac.00735-10

Cited by 71 publications

(50 citation statements)

References 16 publications

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“…Exposure of S. aureus to celecoxib at the MIC of 32 μg/mL after 24 h resulted in a 6-log decrease in CFU relative to that of control (data not shown). In light of the absence of COX-2-like gene in bacteria, 11 this finding suggests that celecoxib’s anti- Staphylococcus activity was dissociated from it effects on COX-2.…”

Section: Resultsmentioning

confidence: 99%

“…8-10 This anti-bacterial effect, however, was not noted with rofecoxib, a more potent COX-2 inhibitor, suggesting the dissociation of these two pharmacological activities. In addition, celecoxib was recently reported to inhibit multidrug resistance in pathogenic bacteria, 11 and has been used to develop a new class of efflux pump inhibitors. 12 In this study, we further demonstrated the unique ability of celecoxib to directly suppress, though with modest potency, the growth of S. aureus, S. epidermidis and MRSA.…”

Section: Introductionmentioning

confidence: 99%

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Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus

Chiu

Su-Lin

Kapuriya

et al. 2012

Bioorganic & Medicinal Chemistry

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Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus

Chiu

Su-Lin

Kapuriya

et al. 2012

Bioorganic & Medicinal Chemistry

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“…We have shown that celecoxib, a cyclooxygenase-2 (COX-2)-specific inhibitor, in combination with an antibiotic increased bacterial sensitivity to the antibiotic [1]. Recently it has been demonstrated that a combination therapy using antibiotics and already approved drugs can overcome bacterial resistance [2].…”

Section: Introductionmentioning

confidence: 99%

Celecoxib Sensitizes Staphylococcus aureus to Antibiotics in Macrophages by Modulating SIRT1

Annamanedi

Kalle

2014

PLoS ONE

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We have previously shown that celecoxib in combination with an antibiotic, increase the bacterial sensitivity to antibiotics. However, the underlying molecular mechanism remained elusive. Efficacy of the combinatorial treatment of celecoxib and ampicillin in vitro was evaluated on macrophage-phagocytosed S aureus. To elucidate the mechanism, signaling pathway of infection and inflammation involving TLR2, JNK, SIRT1 and NF-κB was studied by FACS, Western blot, ELISA and activity assays. Combinatorial treatment of ampicillin and celecoxib reduced the bacterial load in the macrophages. Further studies clearly suggested the activation of the master regulator of oxidative stress and inflammation SIRT1,, by celecoxib when used alone and/or in combination with ampicillin. Also, the results indicated that celecoxib inhibited JNK phosphorylation thereby stabilizing and activating SIRT1 protein that inhibited the COX-2 gene transcription with a significant decrease in the levels of protein inflammatory cytokines like IL-6, MIP-1α and IL-1β via inhibition of NF-κB. SIRT1 activation by celecoxib also resulted in increase of catalase and peroxidase activity with a decrease in Nitric oxide levels. In conclusion, we demonstrate a novel role of celecoxib in controlling inflammation as an enhancer of antibiotic activity against bacteria by modulating SIRT1.

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“…No data about the direct impact of selective COX-2 blockers on gram-positive pathogenic flora are found, but there is an evidence of potentiating effect of celecoxib on sensitivity of S.aureus to antibiotics through increasing of SIRT1 protein regulatory level in macrophages [10] and through inhibiting efflux of antibiotics from a microbial cell [11].…”

Section: оригінальні дослідженняmentioning

confidence: 99%

NSAIDs: can the presence of infectious agent influence the choice of analgesic drug?

Podpletnya¹,

Khomiak²,

Koshova³

2017

Patologìâ

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Purpose. Considering the significant prevalence of comorbid pathology there is a high probability of NSAID use in patients with concomitant infection. In view of this screening of antimicrobial properties of their main groups was conducted for the purpose of selecting the most promising ones for further in-depth study. Materials and methods.The study of microorganisms' sensitivity was conducted using standard research methods -the method of "wells" and by determining the antibacterial properties of drugs, using tablets, based on the ability of the drug to diffuse into agar, used for sowing the test-culture. As the test cultures S. aureus, S. mutans, S. pyogenes, P. aeruginosa, E. Coli, isolated from patients who were treated in hospital were used. Predominant blocker of COX-1 (acetylsalicylic acid, ASA), nonselective blockers of COX-1 and COX-2 (ketorolac, diclofenac sodium, ibuprofen, mefenamic acid, dexketoprofen), predominant blockers of COX-2 (meloxicam and nimesulide), selective blockers of COX-2 (celecoxib), selective blockers of COX-3 (COX-1 in the brain) paracetamol and metamizole were tested.Results. The studies found that most of the tested NSAIDs have antimicrobial activity. Leader drugs in expressiveness of antimicrobial effects are drugs that have sufficient COX-1 (3) -activity: ASA, diclofenac, dexketoprofen, metamizole and lesser extent -paracetamol. Tested NSAIDs showed the highest activity against gram-positive coccal flora, mostly affecting S. Pyogenes. Blockers of COX-3 paracetamol and metamizole, unlike other studied drugs, showed stronger antipseudomonal (both -moderate) and antistaphylococcal action (metamizole).Conclusions. NSAIDs with antimicrobial activity can potentially increase the activity of antiinfectious therapy. At the same time, the antimicrobial activity of NSAIDs, theoretically, can promote microbial resistance because of existence of microorganisms in a medium with subthreshold concentrations of drugs with antimicrobial activity. Considering this, further clinical and pharmacological research of this problem has a great practical importance.НПЗП: чи може наявність інфекційного агента впливати на вибір знеболювального препарату?О. А. Подплетня, О. В. Хомяк, І. П. Кошова Мета роботи -у зв'язку із значною поширеністю коморбідної патології великою є ймовірність застосування НПЗП у хворих, що мають супутній інфекційний процес. З урахуванням цього здійснене скринінгове дослідження антимікробних власти-востей основних груп цих препаратів із ціллю відбору найперспективніших із них для дальшого поглибленого вивчення.Матеріали та методи. Чутливість МО вивчали з використанням стандартних методів дослідження: методу «колодязів» і методу визначення антибактеріальних властивостей препаратів за допомогою таблеток, що заснований на здатності лікарської речовини дифундувати в агар, на який висівали тест-культури. Як тест-культури використовували S. aureus, S. mutans, S. pyogenes, P. aeruginоsa, E. сoli, що виділені від хворих, які перебували на лікуванні у стаціонарі. Протесто-вані переважний...

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Inhibition of Bacterial Multidrug Resistance by Celecoxib, a Cyclooxygenase-2 Inhibitor

Cited by 71 publications

References 16 publications

Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus

Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus

Celecoxib Sensitizes Staphylococcus aureus to Antibiotics in Macrophages by Modulating SIRT1

NSAIDs: can the presence of infectious agent influence the choice of analgesic drug?

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