Treatment of severe pneumonia by hinokitiol in a murine antimicrobial-resistant pneumococcal pneumonia model

Abstract

Streptococcus pneumoniae is often isolated from patients with community-acquired pneumonia. Antibiotics are the primary line of treatment for pneumococcal pneumonia; however, rising antimicrobial resistance is becoming more prevalent. Hinokitiol, which is isolated from trees in the cypress family, has been demonstrated to exert antibacterial activity against S . pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model. Male 8-week-old BALB/c mice were intratracheally infected with S . pneumoniae strains D39 (antimicrobial susceptible) and NU4471 (macrolide resistant). After 1 h, hinokitiol was injected via the tracheal route. Hinokitiol significantly decreased the number of S . pneumoniae in the bronchoalveolar lavage fluid (BALF) and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the infiltration of neutrophils in the lungs, as well as the concentration of inflammatory cytokines in the BALF and serum. Repeated hinokitiol injection at 18 h intervals showed downward trend in the number of S . pneumoniae in the BALF and the concentration of S . pneumoniae DNA in the serum with the number of hinokitiol administrations. These findings suggest that hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Accordingly, hinokitiol warrants further exploration as a potential candidate for the treatment of pneumococcal pneumonia.

Clarithromycin Inhibits Pneumolysin Production via Downregulation of ply Gene Transcription despite Autolysis Activation

“…Following the administration of anesthesia (a mixture of medetomidine hydrochloride [Orion Corporation, Espoo, Finland], midazolam [Sandoz, Tokyo, Japan], and butorphanol [Meiji Seika Pharma Co., Ltd.]), BALB/c mice were intratracheally infected with S. pneumoniae strain NU4471 (5.0 × 10 8 CFU in 50 μl PBS) using a MicroSprayer aerosolizer (Penn-Century, Inc., Philadelphia, PA, USA) as described previously ( 53 ). CLR or ERY powder was dissolved in 5% gum arabic solution.…”

Is Hinokitiol Efficacious Against an Antimicrobial-Resistant Strain of Streptococcus pyogenes? A Research Protocol

“…Considering S. pyogenes (A458) genetic similarity to S. pneumoniae and S. pyogenes (SSI-9), it was found that hinokitiol may have antibacterial effects according to previous studies [4,6]. Therefore, there is reason to believe that hinokitiol affects S. pyogenes (A458) as well.…”

“…Therefore, there is reason to believe that hinokitiol affects S. pyogenes (A458) as well. Hinokitiol has shown to have strong antibacterial effects, making it a suitable candidate [4,6].…”

“…Additionally, A458 is another, highly resistant strain of S. pyogenes, which makes it ideal for comparisons with emm1 when it comes to drug response [2,8]. These two strains will be cultured in Todd Hewitt Broth, an enrichment medium favouring the growth of hemolytic bacteria, such as S. pyogenes, within an Anaerobic Jar at 37°C, as S. pyogenes is an anaerobic coccus and would fail to grow in the presence of oxygen, and 37°C is the most optimal temperature for microbial growth [6].…”

“…Upon reviewing previous literature, hinokitiol has been found to be efficacious against gram-positive bacteria and likely has a different mechanism of action compared to macrolides and penicillin. This makes it a possible alternative and novel treatment in combating a concerning AMR, gram-positive strain of S. pyogenes (A458) with a dwindling number of efficacious treatments [4,[6][7].…”