Mechanism of macrolide-induced inhibition of pneumolysin release involves impairment of autolysin release in macrolide-resistant Streptococcus pneumoniae [Mechanisms of Action]

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia. Over the past two decades, macrolide resistance among S. pneumoniae has been increasing steadily and has escalated at an alarming rate worldwide. However, the use of macrolides in the treatment of community-acquired pneumonia has been reported to be effective regardless of antibiotic susceptibility of the causative pneumococci. Although previous studies suggested that sub-minimum inhibitory concentrations of macrolides inhibit the production of pneumolysin, a pneumococcal pore-forming toxin, by macrolide-resistant S. pneumoniae (MRSP), the underlying mechanisms of the inhibitory effect have not been fully elucidated. Here, we showed that the release of pneumococcal autolysin, which promotes cell lysis and the release of pneumolysin, was inhibited by treatment with azithromycin and erythromycin, whereas replenishing recombinant autolysin restored the release of pneumolysin from MRSP. Additionally, macrolides significantly downregulated ply transcription followed by a slight decrease of intracellular pneumolysin level. These findings suggested the mechanisms involved in the inhibition of pneumolysin in MRSP, which may provide additional explanation for the benefits of macrolides on the outcome of treatment for pneumococcal diseases.

https://ift.tt/2oHVTvu