Repurposing Candesartan Cilexetil as Antibacterial Agent for MRSA Infection

Abstract

Staphylococcus aureus is an important pathogen causing hospital-acquired infections. Methicillin-resistant S. aureus (MRSA), biofilms, and persisters are highly tolerant to traditional antibiotics and make it difficult to treat. Therefore, new antimicrobial agents are urgently needed to treat hard-to-eradicate diseases caused by this bacterium. In this study, candesartan cilexetil (CC), an angiotensin hypertension drug, had strong antimicrobial activity against S. aureus with minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 8–16 μg/ml and 16–32 μg/ml. CC exhibited limited cytotoxicity and low potential to induce drug resistance. In addition, it showed a synergistic antibacterial effect when combined with gentamicin and tobramycin. The effective concentrations to inhibit MRSA biofilm formation were 16–64 μg/ml, and intractable persisters were killed at 4–8 × MIC. Through the analysis of its mechanism of action, it was evident that the membrane permeability was disrupted as well as the cell structure was damaged. Furthermore, we demonstrated that CC had antibacterial effects in vivo in MRSA-infected murine skin abscess models. In conclusion, these results imply that CC might be a potential antibacterial agent for the treatment of S. aureus-associated infections.

Repurposing of the antimalarial agent tafenoquine to combat MRSA

“…FICI ≤0.5 indicates synergism; 0.5 < FICI < 1 indicates partial synergism; FICI = 1 indicates addition; 1 < FICI ≤ 4 indicates indifference; and FICI >4 indicates antagonism ( 25 ).…”

“…S. aureus was grown for 24 h at 37°C and 180 rpm to the stationary phase to obtain persister cells ( 25 ). The persister cells were washed three times with 1 × phosphate-buffered saline (PBS) (pH 7.4), and adjusted to OD 630 = 0.2.…”

Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus

“…Concurrently, the COVID-19 pandemic has potentially diminished the efficacy of certain medications against specific pathogens ( Singh and Sodhi, 2023 ). Consequently, there is heightened concern about multidrug-resistant (MDR) bacteria, especially in bacterial communities frequently exposed to antibiotics ( Xu et al, 2021 ). In recent decades, MDR bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) have become predominant in causing persistent infections across hospitals, communities, and livestock, leading to severe health issues like sepsis, pneumonia, and endocarditis with considerable morbidity and mortality ( Hu et al, 2017 ; Qin et al, 2023 ).…”