Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalis

Calcium hydroxide (Ca(OH)2) is commonly used as a root canal disinfectant, but its effectiveness against Enterococcus faecalis is limited, likely due to the bacterium’s ability to tolerate it. This study aimed to investigate the underlying mechanism of E. faecalis tolerance to repeated exposure to C...

Full description

Saved in:
Bibliographic Details
Main Authors: Zhibo Xu, Haonan Ma, Xinmiao Jiang, Quzhen Baima, Yuqi Zhen, Shipeng Yang, Xiuping Meng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1551824/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850171505350017024
author Zhibo Xu
Zhibo Xu
Haonan Ma
Xinmiao Jiang
Quzhen Baima
Yuqi Zhen
Shipeng Yang
Xiuping Meng
author_facet Zhibo Xu
Zhibo Xu
Haonan Ma
Xinmiao Jiang
Quzhen Baima
Yuqi Zhen
Shipeng Yang
Xiuping Meng
author_sort Zhibo Xu
collection DOAJ
description Calcium hydroxide (Ca(OH)2) is commonly used as a root canal disinfectant, but its effectiveness against Enterococcus faecalis is limited, likely due to the bacterium’s ability to tolerate it. This study aimed to investigate the underlying mechanism of E. faecalis tolerance to repeated exposure to Ca(OH)2. Initially, E. faecalis was exposed to Ca(OH)2 for 10 successive passages. The survival rate of the bacteria increased progressively, suggesting the development of tolerance to Ca(OH)2. Crystal violet staining revealed that calcium hydroxide-tolerant strains formed more robust biofilms compared to standard strains. To delve into the mechanisms of Ca(OH)2 tolerance in E. faecalis, RNA sequencing was employed for a preliminary investigation. Transcriptome sequencing identified 683 differentially expressed genes (DEGs) in the calcium hydroxide-tolerant strain, with 368 genes upregulated and 315 downregulated compared to the standard strain. Bioinformatics analysis revealed that the upregulated genes were associated with carbohydrate transport and metabolism, starch and sucrose metabolism, quorum sensing, aminoacyl-tRNA biosynthesis, and two-component systems signaling pathways. In contrast, the downregulated genes were primarily linked to lipoic acid metabolism, degradation of valine, leucine, and isoleucine, and the citric acid cycle (tricarboxylic acid cycle) signaling pathways. The findings suggest that prolonged exposure to Ca(OH)2 induces tolerance in E. faecalis. RNA sequencing further revealed that this tolerance involves multiple interconnected signaling pathways, providing a critical foundation for future research into therapeutic strategies for E. faecalis infections.
format Article
id doaj-art-436edd56e19a4501bf8de69da64f8669
institution OA Journals
issn 1664-302X
language English
publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Microbiology
spelling doaj-art-436edd56e19a4501bf8de69da64f86692025-08-20T02:20:16ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15518241551824Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalisZhibo Xu0Zhibo Xu1Haonan Ma2Xinmiao Jiang3Quzhen Baima4Yuqi Zhen5Shipeng Yang6Xiuping Meng7Department of Endodontics, Hospital of Stomatology, Jilin University, Changchun, ChinaSchool of Stomatology, Bengbu Medical University, Bengbu, ChinaDepartment of Periodontology, Hospital of Stomatology, Jilin University, Changchun, ChinaDepartment of Endodontics, Hospital of Stomatology, Jilin University, Changchun, ChinaDepartment of Endodontics, Hospital of Stomatology, Jilin University, Changchun, ChinaDepartment of Endodontics, Hospital of Stomatology, Jilin University, Changchun, ChinaDepartment of Endodontics, Hospital of Stomatology, Jilin University, Changchun, ChinaDepartment of Endodontics, Hospital of Stomatology, Jilin University, Changchun, ChinaCalcium hydroxide (Ca(OH)2) is commonly used as a root canal disinfectant, but its effectiveness against Enterococcus faecalis is limited, likely due to the bacterium’s ability to tolerate it. This study aimed to investigate the underlying mechanism of E. faecalis tolerance to repeated exposure to Ca(OH)2. Initially, E. faecalis was exposed to Ca(OH)2 for 10 successive passages. The survival rate of the bacteria increased progressively, suggesting the development of tolerance to Ca(OH)2. Crystal violet staining revealed that calcium hydroxide-tolerant strains formed more robust biofilms compared to standard strains. To delve into the mechanisms of Ca(OH)2 tolerance in E. faecalis, RNA sequencing was employed for a preliminary investigation. Transcriptome sequencing identified 683 differentially expressed genes (DEGs) in the calcium hydroxide-tolerant strain, with 368 genes upregulated and 315 downregulated compared to the standard strain. Bioinformatics analysis revealed that the upregulated genes were associated with carbohydrate transport and metabolism, starch and sucrose metabolism, quorum sensing, aminoacyl-tRNA biosynthesis, and two-component systems signaling pathways. In contrast, the downregulated genes were primarily linked to lipoic acid metabolism, degradation of valine, leucine, and isoleucine, and the citric acid cycle (tricarboxylic acid cycle) signaling pathways. The findings suggest that prolonged exposure to Ca(OH)2 induces tolerance in E. faecalis. RNA sequencing further revealed that this tolerance involves multiple interconnected signaling pathways, providing a critical foundation for future research into therapeutic strategies for E. faecalis infections.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1551824/fullEnterococcus faecaliscalcium hydroxidetolerancepersistent apical periodontitistranscriptomics
spellingShingle Zhibo Xu
Zhibo Xu
Haonan Ma
Xinmiao Jiang
Quzhen Baima
Yuqi Zhen
Shipeng Yang
Xiuping Meng
Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalis
Frontiers in Microbiology
Enterococcus faecalis
calcium hydroxide
tolerance
persistent apical periodontitis
transcriptomics
title Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalis
title_full Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalis
title_fullStr Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalis
title_full_unstemmed Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalis
title_short Transcriptome analysis of calcium hydroxide tolerance in Enterococcus faecalis
title_sort transcriptome analysis of calcium hydroxide tolerance in enterococcus faecalis
topic Enterococcus faecalis
calcium hydroxide
tolerance
persistent apical periodontitis
transcriptomics
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1551824/full
work_keys_str_mv AT zhiboxu transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis
AT zhiboxu transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis
AT haonanma transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis
AT xinmiaojiang transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis
AT quzhenbaima transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis
AT yuqizhen transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis
AT shipengyang transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis
AT xiupingmeng transcriptomeanalysisofcalciumhydroxidetoleranceinenterococcusfaecalis