Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> Persisters

<b>Background</b>: <i>Streptococcus sanguinis</i> 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 bac...

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Main Authors: Kazuya Takada, Yoshie Yoshioka, Kazumasa Morikawa, Wataru Ariyoshi, Ryota Yamasaki
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/1/36
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author Kazuya Takada
Yoshie Yoshioka
Kazumasa Morikawa
Wataru Ariyoshi
Ryota Yamasaki
author_facet Kazuya Takada
Yoshie Yoshioka
Kazumasa Morikawa
Wataru Ariyoshi
Ryota Yamasaki
author_sort Kazuya Takada
collection DOAJ
description <b>Background</b>: <i>Streptococcus sanguinis</i> 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 <i>Streptococcus sanguinis</i> persisters, was investigated. <b>Methods</b>: The bactericidal effects of PCG and GM on <i>S. sanguinis</i> were evaluated. Furthermore, we confirmed whether the <i>S. sanguinis</i> that survived following combination treatment with PCG and GM were persisters. The bactericidal effect of the combination of PCG and GM against <i>S. sanguinis</i> was measured after the addition of glucose or arginine. <b>Results</b>: Following 48 h of treatment with PCG (1600 μg/mL) and GM (64 μg/mL), <i>S. sanguinis</i> 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. <b>Conclusions</b>: Our findings demonstrate that persisters of <i>S. sanguinis</i> that survive antimicrobial treatment may make the treatment of IE challenging, and that combining antimicrobial treatment with glucose is effective for eliminating persisters of <i>S. sanguinis</i>. Taken together, these findings may facilitate the development of novel therapeutic strategies against IE caused by oral streptococcal infection.
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institution Kabale University
issn 2079-6382
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spelling doaj-art-15618137fe214a4196530c323f8b39242025-01-24T13:18:39ZengMDPI AGAntibiotics2079-63822025-01-011413610.3390/antibiotics14010036Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> PersistersKazuya Takada0Yoshie Yoshioka1Kazumasa Morikawa2Wataru Ariyoshi3Ryota Yamasaki4Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, JapanDivision of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, JapanDivision of Oral Functional Development, Department of Health Promotion, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, JapanDivision of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, JapanDivision of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan<b>Background</b>: <i>Streptococcus sanguinis</i> 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 <i>Streptococcus sanguinis</i> persisters, was investigated. <b>Methods</b>: The bactericidal effects of PCG and GM on <i>S. sanguinis</i> were evaluated. Furthermore, we confirmed whether the <i>S. sanguinis</i> that survived following combination treatment with PCG and GM were persisters. The bactericidal effect of the combination of PCG and GM against <i>S. sanguinis</i> was measured after the addition of glucose or arginine. <b>Results</b>: Following 48 h of treatment with PCG (1600 μg/mL) and GM (64 μg/mL), <i>S. sanguinis</i> 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. <b>Conclusions</b>: Our findings demonstrate that persisters of <i>S. sanguinis</i> that survive antimicrobial treatment may make the treatment of IE challenging, and that combining antimicrobial treatment with glucose is effective for eliminating persisters of <i>S. sanguinis</i>. Taken together, these findings may facilitate the development of novel therapeutic strategies against IE caused by oral streptococcal infection.https://www.mdpi.com/2079-6382/14/1/36<i>Streptococcus sanguinis</i>persisterinfective endocarditis
spellingShingle Kazuya Takada
Yoshie Yoshioka
Kazumasa Morikawa
Wataru Ariyoshi
Ryota Yamasaki
Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> Persisters
Antibiotics
<i>Streptococcus sanguinis</i>
persister
infective endocarditis
title Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> Persisters
title_full Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> Persisters
title_fullStr Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> Persisters
title_full_unstemmed Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> Persisters
title_short Glucose Supplementation Enhances the Bactericidal Effect of Penicillin and Gentamicin on <i>Streptococcus sanguinis</i> Persisters
title_sort glucose supplementation enhances the bactericidal effect of penicillin and gentamicin on i streptococcus sanguinis i persisters
topic <i>Streptococcus sanguinis</i>
persister
infective endocarditis
url https://www.mdpi.com/2079-6382/14/1/36
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AT kazumasamorikawa glucosesupplementationenhancesthebactericidaleffectofpenicillinandgentamicinonistreptococcussanguinisipersisters
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