Abstract
Recently, the problem of bacterial resistance has been brought into focus, which makes the development of new antibiotics become a necessity. Compared with traditional development approaches, drug repurposing provides a faster and more effective approach to find new antimicrobial agents. In this study, we found that antispasmodic agent otilonium bromide had strong antibacterial ability and bactericidal activity against Staphylococcus aureus, with minimal inhibitory concentrations (MICs) of 4–8 μg/ml, and bacteria could be killed completely after treatment with 2× MIC of otilonium bromide for 5 h. Furthermore, it had a potent effect on eradicating biofilm at concentrations ranging from 16 to 64 μg/ml. At the same time, it had low tendency to develop resistance and possessed limited cytotoxicity. In the methicillin-resistant S. aureus–infected mouse peritonitis model, it was also effective to cure mice and improve their survival rate. In addition, we observed that otilonium bromide changed the permeability of bacterial membrane and caused membrane damage, and it is probably the antibacterial mechanism of otilonium bromide. Taken together, our results indicated that otilonium bromide could be a new antimicrobial agent to treat S. aureus infections more safely and efficiently.
Highlights
Staphylococcus aureus is a common pathogen that can cause hospital-acquired infections, and its isolation rate was very high among Gram-positive bacteria (Gould et al, 2012)
We found that compared with Gram-negative bacteria, otilonium bromide (OB) had stronger antibacterial activity against Grampositive bacteria, which might be a result of the differences in the composition and structure of the cell wall
polymyxin B nonapeptide (PMBN) had no obvious antibacterial activity as well as bactericidal activity, but it increased the permeability of the outer membrane and promoted the entry of OB into the Gram-negative bacteria (Tsubery et al, 2000)
Summary
Staphylococcus aureus is a common pathogen that can cause hospital-acquired infections, and its isolation rate was very high among Gram-positive bacteria (Gould et al, 2012). It can cause various diseases such as pneumonia, catheter-related infections, and sepsis (David and Daum, 2017). The detection rate of methicillin-resistant S. aureus (MRSA) has risen continuously, which poses a huge challenge to clinical treatment. Most of the drugs discovered through this approach have detailed information about safety and pharmacokinetic profiles, which reduces the cost and time for developing new drugs and accelerates its application in clinical treatment (Miró-Canturri et al, 2019)
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