DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae

Abstract Leprosy, an important infectious disease in humans caused by Mycobacterium leprae (Mle), remains endemic in many countries. Notably, the pathogen cannot be cultured in vitro, except in mouse footpads in vivo. The molecular basis of these characteristics and the mechanisms remain unknown. Co...

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Autores principales:	Hyun Kim, Yasuo Fukutomi, Chie Nakajima, Youn Uck Kim, Shigetarou Mori, Keigo Shibayama, Noboru Nakata, Yasuhiko Suzuki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a3a72a913ac349d5ac56b35039dcfd52
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spelling	oai:doaj.org-article:a3a72a913ac349d5ac56b35039dcfd522021-12-02T16:07:53ZDNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae10.1038/s41598-019-47364-52045-2322https://doaj.org/article/a3a72a913ac349d5ac56b35039dcfd522019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47364-5https://doaj.org/toc/2045-2322Abstract Leprosy, an important infectious disease in humans caused by Mycobacterium leprae (Mle), remains endemic in many countries. Notably, the pathogen cannot be cultured in vitro, except in mouse footpads in vivo. The molecular basis of these characteristics and the mechanisms remain unknown. Consequently, analysis of Mle growth and survival is urgently needed to develop novel therapies against leprosy, including rapid, simple, and specific methods to detect infection. Here, we demonstrated the functional role and contribution of Mle-DNA gyrase, which regulates DNA topology, DNA replication, and chromosome segregation to promote bacterial growth and survival, in Mle growth and survival in vitro and in vivo. The optimum temperature for Mle-DNA gyrase activity was 30 °C. When the DNA gyrB-gyrA genes in Mycobacterium smegmatis were replaced with the Mle gyrase genes by allelic exchange, the recombinants could not grow at 37 °C. Moreover, using radiorespirometry analysis for viability of Mle bacilli, we found that Mle growth was more vigorous at 25–30 °C than at 37 °C, but was inhibited above 40 °C. These results propose that DNA gyrase is a crucial factor for Mle growth and survival and its sensitivity to temperature may be exploited in heat-based treatment of leprosy.Hyun KimYasuo FukutomiChie NakajimaYoun Uck KimShigetarou MoriKeigo ShibayamaNoboru NakataYasuhiko SuzukiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyun Kim Yasuo Fukutomi Chie Nakajima Youn Uck Kim Shigetarou Mori Keigo Shibayama Noboru Nakata Yasuhiko Suzuki DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae
description	Abstract Leprosy, an important infectious disease in humans caused by Mycobacterium leprae (Mle), remains endemic in many countries. Notably, the pathogen cannot be cultured in vitro, except in mouse footpads in vivo. The molecular basis of these characteristics and the mechanisms remain unknown. Consequently, analysis of Mle growth and survival is urgently needed to develop novel therapies against leprosy, including rapid, simple, and specific methods to detect infection. Here, we demonstrated the functional role and contribution of Mle-DNA gyrase, which regulates DNA topology, DNA replication, and chromosome segregation to promote bacterial growth and survival, in Mle growth and survival in vitro and in vivo. The optimum temperature for Mle-DNA gyrase activity was 30 °C. When the DNA gyrB-gyrA genes in Mycobacterium smegmatis were replaced with the Mle gyrase genes by allelic exchange, the recombinants could not grow at 37 °C. Moreover, using radiorespirometry analysis for viability of Mle bacilli, we found that Mle growth was more vigorous at 25–30 °C than at 37 °C, but was inhibited above 40 °C. These results propose that DNA gyrase is a crucial factor for Mle growth and survival and its sensitivity to temperature may be exploited in heat-based treatment of leprosy.
format	article
author	Hyun Kim Yasuo Fukutomi Chie Nakajima Youn Uck Kim Shigetarou Mori Keigo Shibayama Noboru Nakata Yasuhiko Suzuki
author_facet	Hyun Kim Yasuo Fukutomi Chie Nakajima Youn Uck Kim Shigetarou Mori Keigo Shibayama Noboru Nakata Yasuhiko Suzuki
author_sort	Hyun Kim
title	DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae
title_short	DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae
title_full	DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae
title_fullStr	DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae
title_full_unstemmed	DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae
title_sort	dna gyrase could be a crucial regulatory factor for growth and survival of mycobacterium leprae
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/a3a72a913ac349d5ac56b35039dcfd52
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DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae

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