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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Autores principales: Shymaa Enany, Yutaka Yoshida, Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Ohara, Tadashi Yamamoto, Manabu Ato, Sohkichi Matsumoto
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:b89ff17c9d134ae8b29d4b5f0a91e65e2021-12-02T15:05:26ZMycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions10.1038/s41598-017-06480-w2045-2322https://doaj.org/article/b89ff17c9d134ae8b29d4b5f0a91e65e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06480-whttps://doaj.org/toc/2045-2322Abstract 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.Shymaa EnanyYutaka YoshidaYoshitaka TateishiYuriko OzekiAkihito NishiyamaAnna SavitskayaTakehiro YamaguchiYukiko OharaTadashi YamamotoManabu AtoSohkichi MatsumotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
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.
format article
author Shymaa Enany
Yutaka Yoshida
Yoshitaka Tateishi
Yuriko Ozeki
Akihito Nishiyama
Anna Savitskaya
Takehiro Yamaguchi
Yukiko Ohara
Tadashi Yamamoto
Manabu Ato
Sohkichi Matsumoto
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 Portfolio
publishDate 2017
url https://doaj.org/article/b89ff17c9d134ae8b29d4b5f0a91e65e
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