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Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on Streptococcus sanguinis
Kazuya Takada1,2, Yoshie Yoshioka1, Kazumasa Morikawa2
1Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan.
Abstract:
Background: Streptococcus sanguinis is a leading cause of infective endocarditis (IE), which causes diverse clinical symptoms and even death. Recurrence after treatment is a crucial problem in IE, possibly caused by the presence of "persister" cells, a small bacterial population that can survive antimicrobials. In this study, the residual risk for penicillin G (PCG) and gentamicin (GM), used for treating IE, to induce Streptococcus sanguinis persisters, was investigated. Methods: The bactericidal effects of PCG and GM on S. sanguinis were evaluated. Furthermore, we confirmed whether the S. sanguinis that survived following combination treatment with PCG and GM were persisters. The bactericidal effect of the combination of PCG and GM against S. sanguinis was measured after the addition of glucose or arginine. Results: Following 48 h of treatment with PCG (1600 μg/mL) and GM (64 μg/mL), S. sanguinis survived, albeit with a low bacterial count, indicating the presence of persisters. The addition of glucose or arginine to PCG and GM increased the bactericidal effect on residual persister cells and reduced the number of persister cells. Moreover, the addition of glucose at concentrations of 10 mg/mL or higher was substantially effective in achieving sterilization. Conclusions: Our findings demonstrate that persisters of S. sanguinis that survive antimicrobial treatment may make the treatment of IE challenging, and that combining antimicrobial treatment with glucose is effective for eliminating persisters of S. sanguinis. Taken together, these findings may facilitate the development of novel therapeutic strategies against IE caused by oral streptococcal infection.
Insights
Persister cells of Streptococcus sanguinis can survive antibiotic treatment for infective endocarditis. Combining antibiotics with glucose effectively eliminates these persister cells, offering a new therapeutic strategy.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- *Streptococcus sanguinis* is a primary cause of infective endocarditis (IE), a serious condition with potential for recurrence.
- Recurrence in IE is often linked to antibiotic-tolerant "persister" cells.
- Investigating the role of these persisters in IE treatment failure is critical.
Purpose of the Study:
- To evaluate the efficacy of penicillin G (PCG) and gentamicin (GM) in eradicating *Streptococcus sanguinis* persisters.
- To determine if combining PCG and GM with glucose or arginine enhances bactericidal activity against persisters.
- To explore novel therapeutic approaches for IE caused by oral streptococci.
Main Methods:
- Assessing the bactericidal effects of PCG and GM on *S. sanguinis*.
- Confirming the identification of surviving bacteria as persister cells after combination therapy.
- Measuring the impact of glucose or arginine addition on the efficacy of PCG and GM against persisters.
Main Results:
- *S. sanguinis* persister cells were observed to survive 48-hour treatment with PCG and GM.
- The addition of glucose or arginine significantly enhanced the bactericidal effect of PCG and GM on persister cells.
- Glucose, at concentrations of 10 mg/mL or higher, demonstrated substantial effectiveness in sterilizing persister cells.
Conclusions:
- *S. sanguinis* persisters pose a significant challenge in treating IE, contributing to treatment failure.
- Combining standard antibiotic therapy with glucose presents a promising strategy for eliminating IE-associated persister cells.
- These findings may pave the way for developing improved therapeutic regimens for IE.
