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Mechanisms of Action: Physiological Effects

Mechanism of Macrolide-Induced Inhibition of Pneumolysin Release Involves Impairment of Autolysin Release in Macrolide-Resistant Streptococcus pneumoniae

Hisanori Domon, Tomoki Maekawa, Daisuke Yonezawa, Kosuke Nagai, Masataka Oda, Katsunori Yanagihara, Yutaka Terao
Hisanori Domon
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, JapanResearch Center for Advanced Oral Science, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan
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Tomoki Maekawa
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, JapanResearch Center for Advanced Oral Science, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, JapanDivision of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Daisuke Yonezawa
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, JapanResearch Center for Advanced Oral Science, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, JapanDivision of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Kosuke Nagai
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Masataka Oda
Department of Microbiology and Infection Control Sciences, Kyoto Pharmaceutical University, Kyoto, Japan
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Katsunori Yanagihara
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Yutaka Terao
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, JapanResearch Center for Advanced Oral Science, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan
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DOI: 10.1128/AAC.00161-18
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ABSTRACT

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia. Over the past 2 decades, macrolide resistance among S. pneumoniae organisms 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 the antibiotic susceptibility of the causative pneumococci. Although previous studies suggested that sub-MICs of macrolides inhibit the production of the pneumococcal pore-forming toxin pneumolysin by macrolide-resistant S. pneumoniae (MRSP), the underlying mechanisms of the inhibitory effect have not been fully elucidated. Here, we show 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 with recombinant autolysin restored the release of pneumolysin from MRSP. Additionally, macrolides significantly downregulated ply transcription followed by a slight decrease of the intracellular pneumolysin level. These findings suggest the mechanisms involved in the inhibition of pneumolysin in MRSP, which may provide an additional explanation for the benefits of macrolides on the outcome of treatment for pneumococcal diseases.

FOOTNOTES

    • Received 24 January 2018.
    • Returned for modification 18 March 2018.
    • Accepted 27 August 2018.
    • Accepted manuscript posted online 4 September 2018.
  • Supplemental material for this article may be found at https://doi.org/10.1128/AAC.00161-18.

  • Copyright © 2018 American Society for Microbiology.

All Rights Reserved.

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Mechanism of Macrolide-Induced Inhibition of Pneumolysin Release Involves Impairment of Autolysin Release in Macrolide-Resistant Streptococcus pneumoniae
Hisanori Domon, Tomoki Maekawa, Daisuke Yonezawa, Kosuke Nagai, Masataka Oda, Katsunori Yanagihara, Yutaka Terao
Antimicrobial Agents and Chemotherapy Oct 2018, 62 (11) e00161-18; DOI: 10.1128/AAC.00161-18

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Mechanism of Macrolide-Induced Inhibition of Pneumolysin Release Involves Impairment of Autolysin Release in Macrolide-Resistant Streptococcus pneumoniae
Hisanori Domon, Tomoki Maekawa, Daisuke Yonezawa, Kosuke Nagai, Masataka Oda, Katsunori Yanagihara, Yutaka Terao
Antimicrobial Agents and Chemotherapy Oct 2018, 62 (11) e00161-18; DOI: 10.1128/AAC.00161-18
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KEYWORDS

autolysin
azithromycin
community-acquired pneumonia
erythromycin
macrolide-resistant Streptococcus pneumoniae
pneumolysin

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