Control of extensively drug-resistant Pseudomonas aeruginosa co-harboring metallo-β-lactamase enzymes with oprD gene downregulation

El-Sherbiny, Gamal M.; Basha, Amr Mohamad; Mabrouk, Mona I.

doi:10.1016/j.ijmmb.2021.11.002

Cited by 1 publication

(1 citation statement)

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“…Even in cases where the antibiotics had no inhibitory effect, the combination showed some inhibition. This suggests that the selected combination strategy plays a role in reversing drug resistance in P. aeruginosa , and has great potential to fight infections in certain populations because any small or modest increase in antimicrobial activity with combination therapy may contribute to clinical success and recovery in actual clinical practice [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Virtual Screening of Potential RoxS Inhibitors and Evaluation of Their Antimicrobial Activity in Combination with Antibiotics against Clinically Resistant Bacteria

Huang,

Li,

Liang

et al. 2023

Antibiotics

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Pseudomonas aeruginosa with difficult-to-treat resistance has been designated as an urgent or serious threat by the CDC in the United States; therefore, novel antibacterial drugs and combination strategies are urgently needed. The sensor kinase RoxS is necessary for the aerobic growth of Pseudomonas aeruginosa. This study aimed to screen candidate RoxS inhibitors and evaluate their efficacy in treating multi-drug-resistant and extensively drug-resistant Pseudomonas aeruginosa in combination with meropenem and amikacin to identify promising combination strategies. RoxS protein structures were constructed using homology modeling and potential RoxS inhibitors, including Ezetimibe, Deferasirox, and Posaconazole, were screened from the FDA-approved ZINC drug database using molecular docking and molecular dynamics simulations. MIC and checkerboard assays were used to determine the in vitro antimicrobial efficacy of the three drugs in combination with antibiotics. The results of in vitro experiments showed an additive effect of 100 μg/mL Deferasirox or 16 μg/mL Posaconazole in combination with meropenem and a synergistic effect of 1.5 μg/mL Deferasirox and amikacin. In summary, these three drugs are potential inhibitors of RoxS, and their combination with meropenem or amikacin is expected to reverse the resistance of P. aeruginosa, providing new combination strategies for the treatment of clinically difficult-to-treat Pseudomonas aeruginosa.

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Section: Discussionmentioning

confidence: 99%