Abstract
Serious infections caused by multidrug-resistant Staphylococcus aureus clearly urge the development of new antimicrobial agents. Drug repositioning has emerged as an alternative approach that enables us to rapidly identify effective drugs. We first reported a guanidine compound, isopropoxy benzene guanidine, had potent antibacterial activity against S. aureus. Unlike conventional antibiotics, repeated use of isopropoxy benzene guanidine had a lower probability of resistance section. We found that isopropoxy benzene guanidine triggered membrane damage by disrupting the cell membrane potential and cytoplasmic membrane integrity. Furthermore, we demonstrated that isopropoxy benzene guanidine is capable of treating invasive MRSA infections in vivo studies. These findings provided strong evidence that isopropoxy benzene guanidine represents a new chemical lead for novel antibacterial agent against multidrug-resistant S. aureus infections.
Highlights
Antibiotic resistance is one of the most prominent public health challenges (Årdal et al, 2019)
The kill kinetics of isopropoxy benzene guanidine (IBG) was similar to VAN, which greatly reduced the number of bacteria within 4 h (Figures 1B,C)
Staphylococcus aureus infections pose a significant challenge to public health due to the diminishing arsenal of effective antibiotics available
Summary
Antibiotic resistance is one of the most prominent public health challenges (Årdal et al, 2019). Staphylococcus aureus is the most clinically important multidrug-resistant pathogen and a leading cause of bacteremia, endocarditis, osteomyelitis and skin, and soft tissue infections (Tacconelli et al, 2018; Turner et al, 2019). The alarming increase in the prevalence of global spread clones in S. aureus resistant to most antibiotics is a major public health concern (Lakhundi and Zhang, 2018). Antimicrobial drug discovery is under constant challenge. The decreasing rate and huge cost of antibiotic discovery has led to alternative strategies being introduced to the clinic (Antibiotics Currently in Global Clinical Development, 2019). The majority of recently approved agents against S. aureus infections have been developed from existing drug classes, including tetracycline, fluoroquinolone, and pleuromutilin (Talbot et al, 2019). In order to rescue last-resort antibiotics, researchers synthesized vancomycin derivatives by respective or combined modifications, which greatly improved
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