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Effects of macrolides on ultrastructure of Staphylococcus aureus during postantibiotic phase
T Watanabe1, M Kanno, E Tejima
1Pharmaceutical Research Centre, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Abstract:
The postantibiotic effects (PAEs) of macrolide antibiotics, such as midecamycin acetate (Miocamycin, MOM), erythromycin (EM), josamycin (JM) and clarithromycin (CAM), on Staphylococcus aureus and the ultrastructure of the pathogen during the postantibiotic phase were investigated. After exposure to 2 x MIC for 2 h, MOM showed the longest PAE of 3.9 h, while EM, JM and CAM showed PAE durations 1.2, 2.5 and 1.9 h, respectively. On examining the serum levels of these agents in man, the longest PAE of 2.4 h was induced by exposure to MOM. JM and CAM induced PAEs for durations of 1.4 and 1.3 h, but EM hardly induced the PAE. The ultrastructure was examined by transmission electron microscopy, and thick cell walls with an undulating outer layer and a multiple thick cross-section were observed for 4 h after exposure to 2 x MIC of MOM for 2 h. After exposure to 2 x MIC of EM, JM and CAM for 2 h, ultrastructural changes were observed for 1, 2 and 2 h, respectively. The size of these cells was about 1.5 to 2 times larger than the normal cells. Ultrastructural changes in S. aureus were observed during the PAE phase of each macrolide.
Insights
Midecamycin acetate demonstrated the longest postantibiotic effect (PAE) against Staphylococcus aureus, impacting bacterial cell wall structure. Other macrolides like josamycin and clarithromycin also showed significant PAEs and ultrastructural changes.
Area of Science:
- Microbiology
- Pharmacology
- Cell Biology
Background:
- Macrolide antibiotics are crucial for treating bacterial infections.
- Understanding their postantibiotic effects (PAEs) and impact on bacterial ultrastructure is vital for optimizing therapy.
- Staphylococcus aureus is a significant human pathogen requiring effective treatment strategies.
Purpose of the Study:
- To investigate the postantibiotic effects (PAEs) of midecamycin acetate (MOM), erythromycin (EM), josamycin (JM), and clarithromycin (CAM) on Staphylococcus aureus.
- To examine the ultrastructural changes in S. aureus during the PAE phase induced by these macrolides.
- To compare the PAE durations and morphological alterations caused by different macrolide antibiotics.
Main Methods:
- In vitro exposure of Staphylococcus aureus to 2x Minimum Inhibitory Concentration (MIC) of macrolides for 2 hours.
- Measurement of postantibiotic effect (PAE) durations for each antibiotic.
- Transmission electron microscopy (TEM) to analyze ultrastructural changes in bacterial cells during the PAE.
- Evaluation of serum levels and corresponding PAEs in humans.
Main Results:
- Midecamycin acetate (MOM) exhibited the longest PAE in vitro (3.9 h) and in human serum (2.4 h).
- Josamycin (JM) and clarithromycin (CAM) showed moderate PAEs (in vitro: 2.5 h and 1.9 h; serum: 1.4 h and 1.3 h, respectively).
- Erythromycin (EM) demonstrated a shorter PAE (in vitro: 1.2 h; serum: minimal effect).
- Ultrastructural changes, including thickened cell walls and enlarged cell size (1.5-2x), were observed during the PAE phase for all tested macrolides, with MOM inducing changes for a longer duration (4 h).
Conclusions:
- Midecamycin acetate possesses a potent and prolonged postantibiotic effect against Staphylococcus aureus, accompanied by significant and lasting ultrastructural alterations.
- Macrolide antibiotics induce observable changes in Staphylococcus aureus ultrastructure during their respective PAE phases.
- The findings suggest that midecamycin acetate may offer advantages in managing S. aureus infections due to its extended PAE and impact on bacterial morphology.