Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism
The increasing incidence of drug-resistant tuberculosis is still an emergency for global public health and a major obstacle to tuberculosis treatment. Therefore, deciphering the novel mechanisms of mycobacterial antibiotic resistance is crucial for combatting the rapid emergence of drug-resistant st...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.919538/full |
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| author | Wanyan Deng Wanyan Deng Wanyan Deng Zengzhang Zheng Zengzhang Zheng Yi Chen Maoyi Yang Jun Yan Wu Li Wu Li Jie Zeng Jie Zeng Jianping Xie Sitang Gong Sitang Gong Huasong Zeng Huasong Zeng |
| author_facet | Wanyan Deng Wanyan Deng Wanyan Deng Zengzhang Zheng Zengzhang Zheng Yi Chen Maoyi Yang Jun Yan Wu Li Wu Li Jie Zeng Jie Zeng Jianping Xie Sitang Gong Sitang Gong Huasong Zeng Huasong Zeng |
| author_sort | Wanyan Deng |
| collection | DOAJ |
| description | The increasing incidence of drug-resistant tuberculosis is still an emergency for global public health and a major obstacle to tuberculosis treatment. Therefore, deciphering the novel mechanisms of mycobacterial antibiotic resistance is crucial for combatting the rapid emergence of drug-resistant strains. In this study, we identified an unexpected role of Mycobacterium smegmatis GntR family transcriptional regulator MSMEG_5174 and its homologous gene Mycobacterium tuberculosis Rv1152 in aminoglycoside antibiotic resistance. Deficiency of MSMEG_5174 rendered Mycobacterium smegmatis highly resistant to aminoglycoside antibiotic treatment, and ectopic expression of Rv1152 in MSMEG_5174 mutants restored antibiotic-induced bacterial killing. We further demonstrated that MSMEG_5174 negatively regulates the expression of purine metabolism-related genes and the accumulation of purine metabolites. Moreover, overexpression of xanthine dehydrogenase MSMEG_0871 or xanthine treatment elicited a significant decrease in aminoglycoside antibiotic lethality for Mycobacterium smegmatis. Together, our findings revealed MSMEG_5174 as a metabolic regulator and hint toward unexplored crosstalk between purine metabolism and antibiotic resistance. |
| first_indexed | 2024-04-13T14:11:54Z |
| format | Article |
| id | doaj.art-30919d70550b49ac94810b8a5bd68e01 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T14:11:54Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-30919d70550b49ac94810b8a5bd68e012022-12-22T02:43:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-07-011310.3389/fmicb.2022.919538919538Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine MetabolismWanyan Deng0Wanyan Deng1Wanyan Deng2Zengzhang Zheng3Zengzhang Zheng4Yi Chen5Maoyi Yang6Jun Yan7Wu Li8Wu Li9Jie Zeng10Jie Zeng11Jianping Xie12Sitang Gong13Sitang Gong14Huasong Zeng15Huasong Zeng16The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaThe Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaThe Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Respiratory Medicine, The First People’s Hospital of Yunnan Province, Kunming, ChinaAffiliated Hospital of Kunming University of Science and Technology, Kunming, ChinaState Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, ChinaThe Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaThe Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaThe increasing incidence of drug-resistant tuberculosis is still an emergency for global public health and a major obstacle to tuberculosis treatment. Therefore, deciphering the novel mechanisms of mycobacterial antibiotic resistance is crucial for combatting the rapid emergence of drug-resistant strains. In this study, we identified an unexpected role of Mycobacterium smegmatis GntR family transcriptional regulator MSMEG_5174 and its homologous gene Mycobacterium tuberculosis Rv1152 in aminoglycoside antibiotic resistance. Deficiency of MSMEG_5174 rendered Mycobacterium smegmatis highly resistant to aminoglycoside antibiotic treatment, and ectopic expression of Rv1152 in MSMEG_5174 mutants restored antibiotic-induced bacterial killing. We further demonstrated that MSMEG_5174 negatively regulates the expression of purine metabolism-related genes and the accumulation of purine metabolites. Moreover, overexpression of xanthine dehydrogenase MSMEG_0871 or xanthine treatment elicited a significant decrease in aminoglycoside antibiotic lethality for Mycobacterium smegmatis. Together, our findings revealed MSMEG_5174 as a metabolic regulator and hint toward unexplored crosstalk between purine metabolism and antibiotic resistance.https://www.frontiersin.org/articles/10.3389/fmicb.2022.919538/fullMycobacterium smegmatisGntRMSMEG_5174purine metabolismaminoglycoside antibiotics resistance |
| spellingShingle | Wanyan Deng Wanyan Deng Wanyan Deng Zengzhang Zheng Zengzhang Zheng Yi Chen Maoyi Yang Jun Yan Wu Li Wu Li Jie Zeng Jie Zeng Jianping Xie Sitang Gong Sitang Gong Huasong Zeng Huasong Zeng Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism Frontiers in Microbiology Mycobacterium smegmatis GntR MSMEG_5174 purine metabolism aminoglycoside antibiotics resistance |
| title | Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism |
| title_full | Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism |
| title_fullStr | Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism |
| title_full_unstemmed | Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism |
| title_short | Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism |
| title_sort | deficiency of gntr family regulator msmeg 5174 promotes mycobacterium smegmatis resistance to aminoglycosides via manipulating purine metabolism |
| topic | Mycobacterium smegmatis GntR MSMEG_5174 purine metabolism aminoglycoside antibiotics resistance |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.919538/full |
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