The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>

Chlorhexidine (CHX) is widely considered to be the gold standard for preventing dental caries. However, it is possible to induce resistance to CHX. The LiaSR two-component system has been identified that contributed to CHX resistance in <i>Streptococcus mutans</i>, which is one of the ma...

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Main Authors: Shan Huang, Jing Huang, Jingyun Du, Yijun Li, Minjing Wu, Shuai Chen, Ling Zhan, Xiaojing Huang
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/12/3/468
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author Shan Huang
Jing Huang
Jingyun Du
Yijun Li
Minjing Wu
Shuai Chen
Ling Zhan
Xiaojing Huang
author_facet Shan Huang
Jing Huang
Jingyun Du
Yijun Li
Minjing Wu
Shuai Chen
Ling Zhan
Xiaojing Huang
author_sort Shan Huang
collection DOAJ
description Chlorhexidine (CHX) is widely considered to be the gold standard for preventing dental caries. However, it is possible to induce resistance to CHX. The LiaSR two-component system has been identified that contributed to CHX resistance in <i>Streptococcus mutans</i>, which is one of the major pathogens in dental caries. However, the underlying mechanisms remain unclear. In this study, an MIC assay and a viability assessment demonstrated that after deleting the <i>liaS</i> and <i>liaR</i> genes, the sensitivity of mutants could increase. The Nile Red efflux assay exhibited that the efflux rates of mutants were significantly decreased. The RT-qPCR results indicated that the LiaSR two-component system-mediating influence on the expression of <i>lmrB</i> in <i>S. mutans</i> contributed to the efflux rate. The hydrophobicity assay and membrane potential assay showed that the mutants had higher levels of hydrophobicity and depolarization, suggesting that their membranes were more easily disturbed. The TEM graphs revealed that the border of the cell membrane was unclear in mutants compared with the wild-type strain, indicating that the cell envelope’s stress response may have been inhibited. While the surface charge of mutants showed no significant difference in the wild-type strain according to the result of cytochrome c-based charged determination. This study provides valuable novel insights into the mechanisms of the LiaSR two-component system in the CHX resistance of <i>S. mutans</i>.
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spelling doaj.art-deeb7c0106a440bd99b97724fdae52e12024-03-27T13:55:33ZengMDPI AGMicroorganisms2076-26072024-02-0112346810.3390/microorganisms12030468The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>Shan Huang0Jing Huang1Jingyun Du2Yijun Li3Minjing Wu4Shuai Chen5Ling Zhan6Xiaojing Huang7Fujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial, Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, ChinaFujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial, Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, ChinaFujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial, Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, ChinaFujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial, Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, ChinaFujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial, Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, ChinaFujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial, Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, ChinaDivision of Pediatric Dentistry, Department of Orofacial Sciences, University of California, San Francisco, CA 94143, USAFujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial, Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou 350002, ChinaChlorhexidine (CHX) is widely considered to be the gold standard for preventing dental caries. However, it is possible to induce resistance to CHX. The LiaSR two-component system has been identified that contributed to CHX resistance in <i>Streptococcus mutans</i>, which is one of the major pathogens in dental caries. However, the underlying mechanisms remain unclear. In this study, an MIC assay and a viability assessment demonstrated that after deleting the <i>liaS</i> and <i>liaR</i> genes, the sensitivity of mutants could increase. The Nile Red efflux assay exhibited that the efflux rates of mutants were significantly decreased. The RT-qPCR results indicated that the LiaSR two-component system-mediating influence on the expression of <i>lmrB</i> in <i>S. mutans</i> contributed to the efflux rate. The hydrophobicity assay and membrane potential assay showed that the mutants had higher levels of hydrophobicity and depolarization, suggesting that their membranes were more easily disturbed. The TEM graphs revealed that the border of the cell membrane was unclear in mutants compared with the wild-type strain, indicating that the cell envelope’s stress response may have been inhibited. While the surface charge of mutants showed no significant difference in the wild-type strain according to the result of cytochrome c-based charged determination. This study provides valuable novel insights into the mechanisms of the LiaSR two-component system in the CHX resistance of <i>S. mutans</i>.https://www.mdpi.com/2076-2607/12/3/468<i>Streptococcus mutans</i>LiaSR two-component systemchlorhexidine resistanceefflux pumpcells envelope stress responses
spellingShingle Shan Huang
Jing Huang
Jingyun Du
Yijun Li
Minjing Wu
Shuai Chen
Ling Zhan
Xiaojing Huang
The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>
Microorganisms
<i>Streptococcus mutans</i>
LiaSR two-component system
chlorhexidine resistance
efflux pump
cells envelope stress responses
title The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>
title_full The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>
title_fullStr The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>
title_full_unstemmed The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>
title_short The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in <i>Streptococcus mutans</i>
title_sort liasr two component system regulates resistance to chlorhexidine in i streptococcus mutans i
topic <i>Streptococcus mutans</i>
LiaSR two-component system
chlorhexidine resistance
efflux pump
cells envelope stress responses
url https://www.mdpi.com/2076-2607/12/3/468
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