Montelukast treats Streptococcus pneumoniae-induced sepsis via antibacterial and anti-inflammatory activities
Abstract
Streptococcus pneumoniae is a leading causative pathogen of community-acquired pneumonia and sepsis. The increasing prevalence of antibiotic resistance among S. pneumoniae strains poses a major challenge to conventional antibiotic therapies. This study aimed to systematically evaluate the antibacterial, anti-biofilm, and in vivo therapeutic effects of montelukast against S. pneumoniae and to explore its potential for drug repurposing as an anti-infective agent. In vitro susceptibility testing revealed that montelukast exhibited inhibitory activity against both standard reference strains and 11 clinical multidrug-resistant (MDR) S. pneumoniae isolates, with minimum inhibitory concentrations (MICs) ranging from 4 to 32 µg/mL. Time-kill assays using the representative MDR strain S12 showed that montelukast at 16 µg/mL could completely eradicate bacteria within 8 h. And biofilm assays further demonstrated that montelukast at concentrations of 8-16 µg/mL significantly disrupted preformed biofilms and reduced viable bacterial counts within mature biofilms, suggesting its potential to combat chronic infections. In a mouse model of sepsis, montelukast treatment significantly improved survival rates of infected mice, with the 10 mg/kg dosage group achieving a 7-day survival rate of 80%. Quantification of bacterial burden revealed a marked reduction in colony-forming units (CFUs) in both blood and lung of montelukast-treated mice. Furthermore, analysis of serum inflammatory cytokines…
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