Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo

ABSTRACT Caries are chronic infections in which the cariogenic biofilm plays a critical role in disease occurrence and progression. Photodynamic therapy (PDT) is a new effective treatment that is receiving wide attention in the antibacterial field, but it can lead to the upregulation of heat shock p...

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Main Authors: Zichen Zhang, Yaoting Ji, Danfeng Liu, Shuhui Zhou, Zijun Wang, Rourong Chen, Ting Li, Boxuan Zhao, Hantao Yao, Minquan Du
Format: Article
Language:English
Published: American Society for Microbiology 2023-04-01
Series:mSphere
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/msphere.00679-22
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author Zichen Zhang
Yaoting Ji
Danfeng Liu
Shuhui Zhou
Zijun Wang
Rourong Chen
Ting Li
Boxuan Zhao
Hantao Yao
Minquan Du
author_facet Zichen Zhang
Yaoting Ji
Danfeng Liu
Shuhui Zhou
Zijun Wang
Rourong Chen
Ting Li
Boxuan Zhao
Hantao Yao
Minquan Du
author_sort Zichen Zhang
collection DOAJ
description ABSTRACT Caries are chronic infections in which the cariogenic biofilm plays a critical role in disease occurrence and progression. Photodynamic therapy (PDT) is a new effective treatment that is receiving wide attention in the antibacterial field, but it can lead to the upregulation of heat shock proteins (HSPs), which enhances bacterial resistance. Herein, we incorporated HSP inhibitors with PDT to evaluate the effect on Streptococcus mutans, Streptococcus sobrinus, and Streptococcus sanguinis under planktonic conditions and on cariogenic biofilms. Additionally, a model of caries was established in 2-week-old rats, and anticaries properties were evaluated by Keyes’ scoring. Importantly, the combination of HSP inhibitors and PDT had outstanding efficiency in inhibiting the growth of tested Streptococcus strains and the formation of either monomicrobial or multispecies biofilms in vitro. In addition, the quantity of colonized streptococci and the severity of carious lesions were also distinctly suppressed in vivo. Overall, the synergistic application of HSP inhibitors and PDT has promising potential in the prevention and treatment of dental caries. IMPORTANCE Effective therapies for the prevention and control of caries are urgently needed. Cariogenic streptococci play a key role in the occurrence and progression of caries. Recently, photodynamic therapy has been demonstrated to have good antibacterial efficiency, but it can cause a heat shock response in bacteria, which may weaken its practical effects. We indicate here an effective therapeutic strategy of combining heat shock protein inhibitors and photodynamic therapy, which shows excellent inhibition toward three dominant streptococci related to caries and suppression of carious progression in a rat model. Further development for clinical application is promising.
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spelling doaj.art-21920600e1fa4863a3950de27f1bc08b2023-04-20T13:01:45ZengAmerican Society for MicrobiologymSphere2379-50422023-04-018210.1128/msphere.00679-22Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In VivoZichen Zhang0Yaoting Ji1Danfeng Liu2Shuhui Zhou3Zijun Wang4Rourong Chen5Ting Li6Boxuan Zhao7Hantao Yao8Minquan Du9The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaABSTRACT Caries are chronic infections in which the cariogenic biofilm plays a critical role in disease occurrence and progression. Photodynamic therapy (PDT) is a new effective treatment that is receiving wide attention in the antibacterial field, but it can lead to the upregulation of heat shock proteins (HSPs), which enhances bacterial resistance. Herein, we incorporated HSP inhibitors with PDT to evaluate the effect on Streptococcus mutans, Streptococcus sobrinus, and Streptococcus sanguinis under planktonic conditions and on cariogenic biofilms. Additionally, a model of caries was established in 2-week-old rats, and anticaries properties were evaluated by Keyes’ scoring. Importantly, the combination of HSP inhibitors and PDT had outstanding efficiency in inhibiting the growth of tested Streptococcus strains and the formation of either monomicrobial or multispecies biofilms in vitro. In addition, the quantity of colonized streptococci and the severity of carious lesions were also distinctly suppressed in vivo. Overall, the synergistic application of HSP inhibitors and PDT has promising potential in the prevention and treatment of dental caries. IMPORTANCE Effective therapies for the prevention and control of caries are urgently needed. Cariogenic streptococci play a key role in the occurrence and progression of caries. Recently, photodynamic therapy has been demonstrated to have good antibacterial efficiency, but it can cause a heat shock response in bacteria, which may weaken its practical effects. We indicate here an effective therapeutic strategy of combining heat shock protein inhibitors and photodynamic therapy, which shows excellent inhibition toward three dominant streptococci related to caries and suppression of carious progression in a rat model. Further development for clinical application is promising.https://journals.asm.org/doi/10.1128/msphere.00679-22carieschlorin e6heat shock protein inhibitorsphotodynamic therapyStreptococcus
spellingShingle Zichen Zhang
Yaoting Ji
Danfeng Liu
Shuhui Zhou
Zijun Wang
Rourong Chen
Ting Li
Boxuan Zhao
Hantao Yao
Minquan Du
Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo
mSphere
caries
chlorin e6
heat shock protein inhibitors
photodynamic therapy
Streptococcus
title Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo
title_full Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo
title_fullStr Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo
title_full_unstemmed Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo
title_short Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo
title_sort heat shock protein inhibitors show synergistic antibacterial effects with photodynamic therapy on caries related streptococci in vitro and in vivo
topic caries
chlorin e6
heat shock protein inhibitors
photodynamic therapy
Streptococcus
url https://journals.asm.org/doi/10.1128/msphere.00679-22
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