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Repositioning of a mucolytic drug to a selective antibacterial against Vibrio cholerae
In-Young Chung† , Bi-o Kim† , Hye-Jeong Jang† , You-Hee Cho
J. Microbiol. 2020;58(1):61-66.   Published online January 2, 2020
DOI: https://doi.org/10.1007/s12275-020-9590-9
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  • 1 Web of Science
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AbstractAbstract
Drug repositioning, the approach to explore existing drugs for use in new therapeutic indications, has emerged as an alternative drug development strategy. In this study, we found that a mucolytic drug, N-acetylcysteine (NAC) showed antibacterial activity against Vibrio cholerae. NAC can provide acid stress that selectively inhibited the growth of V. cholerae among other bacterial pathogens. To address the antibacterial mechanism of NAC against V. cholerae, six acr (acetylcysteine- resistant) mutants were isolated from 3,118 random transposon insertion clones. The transposon insertion sites of the six mutants were mapped at the five genes. All these mutants did not display NAC resistance under acidic conditions, despite their resistance to NAC under alkaline conditions, indicating that the NAC resistance directed by the acr mutations was independent of the unusual pH-sensitivity of V. cholerae. Furthermore, all these mutants displayed attenuated virulence and reduced biofilm formation, suggesting that the acr genes are required for pathogenesis of V. cholerae. This study validates the relevance of drug repositioning for antibacterials with new modes of action and will provide an insight into a novel antibacterial therapy for V. cholerae infections to minimize side effects and resistance emergence.

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  • Identification of brevinin-1EMa-derived stapled peptides as broad-spectrum virus entry blockers
    Mi Il Kim, Thanh K. Pham, Dahee Kim, Minkyung Park, Bi-o Kim, You-Hee Cho, Young-Woo Kim, Choongho Lee
    Virology.2021; 561: 6.     CrossRef
N-acetylcysteine prevents the development of gastritis induced by Helicobacter pylori infection
Sungil Jang , Eun-Jung Bak , Jeong-Heon Cha
J. Microbiol. 2017;55(5):396-402.   Published online April 29, 2017
DOI: https://doi.org/10.1007/s12275-017-7089-9
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  • 13 Crossref
AbstractAbstract
Helicobacter pylori (H. pylori) is a human gastric pathogen, causing various gastric diseases ranging from gastritis to gas-tric adenocarcinoma. It has been reported that combining N-acetylcysteine (NAC) with conventional antibiotic therapy increases the success rate of H. pylori eradication. We evalu-ated the effect of NAC itself on the growth and coloniza-tion of H. pylori, and development of gastritis, using in vitro liquid culture system and in vivo animal models. H. pylori growth was evaluated in broth culture containing NAC. The H. pylori load and histopathological scores of stomachs were measured in Mongolian gerbils infected with H. pylori strain 7.13, and fed with NAC-containing diet. In liquid culture, NAC inhibited H. pylori growth in a concentration-depen-dent manner. In the animal model, 3-day administration of NAC after 1 week from infection reduced the H. pylori load; 6-week administration of NAC after 1 week from infection prevented the development of gastritis and reduced H. pylori colonization. However, no reduction in the bacterial load or degree of gastritis was observed with a 6-week administ-ration of NAC following 6-week infection period. Our results indicate that NAC may exert a beneficial effect on reduction of bacterial colonization, and prevents the development of severe inflammation, in people with initial asymptomatic or mild H. pylori infection.

Citations

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  • Role of N-acetylcysteine and vitamin B complex in improving outcomes of corrosive ingestion
    Heidi El-Sobky, Safaa Mostafa El-Shanawany, Maha Ghanem, Maram Atef
    Toxicology Research.2024;[Epub]     CrossRef
  • Helicobacter pylori: Routes of Infection, Antimicrobial Resistance, and Alternative Therapies as a Means to Develop Infection Control
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    Maia J. Baskerville, Yekaterina Kovalyova, Raquel Mejías-Luque, Markus Gerhard, Stavroula K. Hatzios, William Navarre
    PLOS Pathogens.2023; 19(7): e1011526.     CrossRef
  • Helicobacter pylori-mediated gastric pathogenesis is attenuated by treatment of 2-deoxyglucose and metformin
    Hanfu Su, Eun-Jung Bak, Aeryun Kim, Kavinda Tissera, Jeong-Heon Cha, Sungil Jang
    Journal of Microbiology.2022; 60(8): 849.     CrossRef
  • Population Pharmacokinetics of Doxycycline, Administered Alone or with N-Acetylcysteine, in Chickens with Experimental Mycoplasma gallisepticum Infection
    Tsvetelina Petkova, Antoaneta Yordanova, Aneliya Milanova
    Pharmaceutics.2022; 14(11): 2440.     CrossRef
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    Gerry K. Schwalfenberg, Tatiana Emanuelli
    Journal of Nutrition and Metabolism.2021; 2021: 1.     CrossRef
  • Enhanced Eradication of Mucin‐Embedded Bacterial Biofilm by Locally Delivered Antibiotics in Functionalized Microcontainers
    Stine Egebro Birk, Laura Serioli, Valentina Cavallo, Janus Anders Juul Haagensen, Søren Molin, Line Hagner Nielsen, Kinga Zór, Anja Boisen
    Macromolecular Bioscience.2021;[Epub]     CrossRef
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    Micaely Cristina dos Santos Tenório, Nayara Gomes Graciliano, Fabiana Andréa Moura, Alane Cabral Menezes de Oliveira, Marília Oliveira Fonseca Goulart
    Antioxidants.2021; 10(6): 967.     CrossRef
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    Ana I Rodríguez-Rosado, Estela Ynés Valencia, Alexandro Rodríguez-Rojas, Coloma Costas, Rodrigo S Galhardo, Jerónimo Rodríguez-Beltrán, Jesús Blázquez
    Journal of Antimicrobial Chemotherapy.2019; 74(8): 2188.     CrossRef
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    Jing Cui, Li Tang, Quan Hong, Shupeng Lin, Xuefeng Sun, Guangyan Cai, Xue-Yuan Bai, Xiangmei Chen
    Shock.2019; 52(6): 622.     CrossRef
  • Allantoin improves histopathological evaluations in a rat model of gastritis
    M Eslami-farsani, A Moslehi, A Hatami-shahmir
    Physiology International.2018; 105(4): 325.     CrossRef
  • N‐Acetylcysteine Reduces ROS‐Mediated Oxidative DNA Damage and PI3K/Akt Pathway Activation Induced by Helicobacter pylori Infection
    Chuan Xie, Jian Yi, Jing Lu, Muwen Nie, Meifang Huang, Jianfang Rong, Zhenhua Zhu, Jiang Chen, Xiaoliang Zhou, Bimin Li, Haiming Chen, Nonghua Lu, Xu Shu, Rômulo D. Novaes
    Oxidative Medicine and Cellular Longevity.2018;[Epub]     CrossRef
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    Le Guo, Hua Yang, Feng Tang, Runting Yin, Hongpeng Liu, Xiaojuan Gong, Jun Wei, Ying Zhang, Guangxian Xu, Kunmei Liu
    Frontiers in Cellular and Infection Microbiology.2017;[Epub]     CrossRef
Research Support, Non-U.S. Gov't
Antibacterial effects of N-acetylcysteine against endodontic pathogens
Ji-Hoi Moon , Young-Suk Choi , Hyeon-Woo Lee , Jung Sun Heo , Seok Woo Chang , Jin-Yong Lee
J. Microbiol. 2016;54(4):322-329.   Published online April 1, 2016
DOI: https://doi.org/10.1007/s12275-016-5534-9
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  • 0 Download
  • 30 Crossref
AbstractAbstract
The success of endodontic treatment depends on the eradication of microorganisms from the root canal system and the prevention of reinfection. The purpose of this investigation was to evaluate the antibacterial and antibiofilm efficacy of N-acetylcysteine (NAC), an antioxidant mucolytic agent, as an intracanal medicament against selected endodontic pathogens. Minimum inhibitory concentrations (MICs) of NAC for Actinomyces naeslundii, Lactobacillus salivarius, Streptococcus mutans, and Enterococcus faecalis were determined using the broth microdilution method. NAC showed antibacterial activity, with MIC values of 0.78–1.56 mg/ml. The effect of NAC on biofilm formation of each bacterium and a multispecies culture consisting of the four bacterial species was assessed by crystal violet staining. NAC significantly inhibited biofilm formation by all the monospecies and multispecies bacteria at minimum concentrations of 0.78–3.13 mg/ml. The efficacy of NAC for biofilm disruption was evaluated by scanning electron microscopy and ATP-bioluminescence quantification using mature multispecies biofilms. Preformed mature multispecies biofilms on saliva-coated hydroxyapatite disks were disrupted within 10 min by treatment with NAC at concentrations of 25 mg/ml or higher. After 24 h of treatment, the viability of mature biofilms was reduced by > 99% compared with the control. Moreover, the biofilm disrupting activity of NAC was significantly higher than that of saturated calcium hydroxide or 2% chlorhexidine solution. Within the limitations of this in vitro study, we conclude that NAC has excellent antibacterial and antibiofilm efficacy against endodontic pathogens and may be used as an alternative intracanal medicament in root canal therapies.

Citations

Citations to this article as recorded by  
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    Rayana Duarte Khoury, Amjad Abu Hasna, Carolina Fedel Gagliardi, Renata Marques de Melo Marinho, Cláudio Antonio Talge Carvalho, Eduardo Bresciani, Marcia Carneiro Valera
    PeerJ.2024; 12: e18331.     CrossRef
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    Pranjali S. Narvekar, Shruthi Velmurugan, Preeti K Doddwad, Sunita Shivanand
    IP Indian Journal of Conservative and Endodontics.2024; 9(2): 70.     CrossRef
  • In Vitro Antimicrobial Activity of N-Acetylcysteine against Pathogens Most Commonly Associated with Infectious Keratitis in Dogs and Cats
    Hanna Walter, Jutta Verspohl, Jessica Meißner, Hilke Oltmanns, Anna Karoline Geks, Claudia Busse
    Antibiotics.2023; 12(3): 559.     CrossRef
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    Kai Zhang, Cheng He, Yuan Qiu, Xiuyang Li, Jian Hu, Baiping Fu
    Journal of Evidence-Based Dental Practice.2023; 23(3): 101897.     CrossRef
  • Effect of Nebulized BromAc on Rheology of Artificial Sputum: Relevance to Muco-Obstructive Respiratory Diseases
    Krishna Pillai, Ahmed H. Mekkawy, Javed Akhter, David L. Morris
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    Sophie Tieu, Armen Charchoglyan, Lauryn Paulsen, Lauri C. Wagter-Lesperance, Umesh K. Shandilya, Byram W. Bridle, Bonnie A. Mallard, Niel A. Karrow
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    Current Microbiology.2022;[Epub]     CrossRef
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    Alireza Adl, Mohammad Motamedifar, Parastoo Malekzadeh, Mahdi Sedigh‐Shams
    Australian Endodontic Journal.2022; 48(3): 386.     CrossRef
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    B. J. M. Corazza, F. C. Martinho, R. D. Khoury, C. C. Toia, E. I. F. Orozco, R. F. Prado, F. P. Machado, M. C. Valera
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