Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions
Abstract Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent...
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doaj-b89ff17c9d134ae8b29d4b5f0a91e65e2020-12-08T02:19:18ZengNature Publishing GroupScientific Reports2045-23222017-07-017111110.1038/s41598-017-06480-wMycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functionsShymaa Enany0Yutaka Yoshida1Yoshitaka Tateishi2Yuriko Ozeki3Akihito Nishiyama4Anna Savitskaya5Takehiro Yamaguchi6Yukiko Ohara7Tadashi Yamamoto8Manabu Ato9Sohkichi Matsumoto10Department of Bacteriology, Niigata University School of MedicineDepartment of Structural Pathology, Kidney Research CenterDepartment of Bacteriology, Niigata University School of MedicineDepartment of Bacteriology, Niigata University School of MedicineDepartment of Bacteriology, Niigata University School of MedicineDepartment of Bacteriology, Niigata University School of MedicineDepartment of Bacteriology, Niigata University School of MedicineDepartment of Bacteriology, Niigata University School of MedicineBiofluid Biomarker Center, Institute of Social innovation and Co-operation, Niigata UniversityDepartment of Immunology, National Institute of Infectious DiseasesDepartment of Bacteriology, Niigata University School of MedicineAbstract Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent infections. However, the fundamental mechanisms of the long-term living of mycobacteria are unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein 1 (MDP1), a histone-like nucleoid associated protein. Mycobacterium smegmatis is a saprophytic fast grower and used as a model of mycobacterial persistence, since it shares the characteristics of the long-term survival observed in pathogenic mycobacteria. Here we show that MDP1-deficient M. smegmatis dies more rapidly than the parental strain after entering stationary phase. Proteomic analyses revealed 21 upregulated proteins with more than 3-fold in MDP1-deficient strain, including DnaA, a replication initiator, NDH, a NADH dehydrogenase that catalyzes downhill electron transfer, Fas1, a critical fatty acid synthase, and antioxidants such as AhpC and KatG. Biochemical analyses showed elevated levels of DNA and ATP syntheses, a decreased NADH/NAD+ ratio, and a loss of resistance to oxidative stress in the MDP1-knockout strain. This study suggests the importance of MDP1-dependent simultaneous control of the cellular functions in the long-term survival of mycobacteria.https://doi.org/10.1038/s41598-017-06480-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shymaa Enany Yutaka Yoshida Yoshitaka Tateishi Yuriko Ozeki Akihito Nishiyama Anna Savitskaya Takehiro Yamaguchi Yukiko Ohara Tadashi Yamamoto Manabu Ato Sohkichi Matsumoto |
spellingShingle |
Shymaa Enany Yutaka Yoshida Yoshitaka Tateishi Yuriko Ozeki Akihito Nishiyama Anna Savitskaya Takehiro Yamaguchi Yukiko Ohara Tadashi Yamamoto Manabu Ato Sohkichi Matsumoto Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions Scientific Reports |
author_facet |
Shymaa Enany Yutaka Yoshida Yoshitaka Tateishi Yuriko Ozeki Akihito Nishiyama Anna Savitskaya Takehiro Yamaguchi Yukiko Ohara Tadashi Yamamoto Manabu Ato Sohkichi Matsumoto |
author_sort |
Shymaa Enany |
title |
Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions |
title_short |
Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions |
title_full |
Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions |
title_fullStr |
Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions |
title_full_unstemmed |
Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions |
title_sort |
mycobacterial dna-binding protein 1 is critical for long term survival of mycobacterium smegmatis and simultaneously coordinates cellular functions |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-07-01 |
description |
Abstract Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent infections. However, the fundamental mechanisms of the long-term living of mycobacteria are unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein 1 (MDP1), a histone-like nucleoid associated protein. Mycobacterium smegmatis is a saprophytic fast grower and used as a model of mycobacterial persistence, since it shares the characteristics of the long-term survival observed in pathogenic mycobacteria. Here we show that MDP1-deficient M. smegmatis dies more rapidly than the parental strain after entering stationary phase. Proteomic analyses revealed 21 upregulated proteins with more than 3-fold in MDP1-deficient strain, including DnaA, a replication initiator, NDH, a NADH dehydrogenase that catalyzes downhill electron transfer, Fas1, a critical fatty acid synthase, and antioxidants such as AhpC and KatG. Biochemical analyses showed elevated levels of DNA and ATP syntheses, a decreased NADH/NAD+ ratio, and a loss of resistance to oxidative stress in the MDP1-knockout strain. This study suggests the importance of MDP1-dependent simultaneous control of the cellular functions in the long-term survival of mycobacteria. |
url |
https://doi.org/10.1038/s41598-017-06480-w |
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