Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.

Mycoplasmas are minute bacteria controlled by very small genomes ranging from 0.6 to 1.4 Mbp. They encompass several important medical and veterinary pathogens that are often associated with a wide range of chronic diseases. The long persistence of mycoplasma cells in their hosts can exacerbate the...

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Autores principales:	Virginia Hill, Hatice Akarsu, Rubén Sánchez Barbarroja, Valentina L Cippà, Peter Kuhnert, Martin Heller, Laurent Falquet, Manfred Heller, Michael H Stoffel, Fabien Labroussaa, Joerg Jores
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/cbe8f8f61d5b4ecf874e6a333c7b4b94
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spelling	oai:doaj.org-article:cbe8f8f61d5b4ecf874e6a333c7b4b942021-12-02T20:03:30ZMinimalistic mycoplasmas harbor different functional toxin-antitoxin systems.1553-73901553-740410.1371/journal.pgen.1009365https://doaj.org/article/cbe8f8f61d5b4ecf874e6a333c7b4b942021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009365https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Mycoplasmas are minute bacteria controlled by very small genomes ranging from 0.6 to 1.4 Mbp. They encompass several important medical and veterinary pathogens that are often associated with a wide range of chronic diseases. The long persistence of mycoplasma cells in their hosts can exacerbate the spread of antimicrobial resistance observed for many species. However, the nature of the virulence factors driving this phenomenon in mycoplasmas is still unclear. Toxin-antitoxin systems (TA systems) are genetic elements widespread in many bacteria that were historically associated with bacterial persistence. Their presence on mycoplasma genomes has never been carefully assessed, especially for pathogenic species. Here we investigated three candidate TA systems in M. mycoides subsp. capri encoding a (i) novel AAA-ATPase/subtilisin-like serine protease module, (ii) a putative AbiEii/AbiEi pair and (iii) a putative Fic/RelB pair. We sequence analyzed fourteen genomes of M. mycoides subsp. capri and confirmed the presence of at least one TA module in each of them. Interestingly, horizontal gene transfer signatures were also found in several genomic loci containing TA systems for several mycoplasma species. Transcriptomic and proteomic data confirmed differential expression profiles of these TA systems during mycoplasma growth in vitro. While the use of heterologous expression systems based on E. coli and B. subtilis showed clear limitations, the functionality and neutralization capacities of all three candidate TA systems were successfully confirmed using M. capricolum subsp. capricolum as a host. Additionally, M. capricolum subsp. capricolum was used to confirm the presence of functional TA system homologs in mycoplasmas of the Hominis and Pneumoniae phylogenetic groups. Finally, we showed that several of these M. mycoides subsp. capri toxins tested in this study, and particularly the subtilisin-like serine protease, could be used to establish a kill switch in mycoplasmas for industrial applications.Virginia HillHatice AkarsuRubén Sánchez BarbarrojaValentina L CippàPeter KuhnertMartin HellerLaurent FalquetManfred HellerMichael H StoffelFabien LabroussaaJoerg JoresPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 10, p e1009365 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Virginia Hill Hatice Akarsu Rubén Sánchez Barbarroja Valentina L Cippà Peter Kuhnert Martin Heller Laurent Falquet Manfred Heller Michael H Stoffel Fabien Labroussaa Joerg Jores Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.
description	Mycoplasmas are minute bacteria controlled by very small genomes ranging from 0.6 to 1.4 Mbp. They encompass several important medical and veterinary pathogens that are often associated with a wide range of chronic diseases. The long persistence of mycoplasma cells in their hosts can exacerbate the spread of antimicrobial resistance observed for many species. However, the nature of the virulence factors driving this phenomenon in mycoplasmas is still unclear. Toxin-antitoxin systems (TA systems) are genetic elements widespread in many bacteria that were historically associated with bacterial persistence. Their presence on mycoplasma genomes has never been carefully assessed, especially for pathogenic species. Here we investigated three candidate TA systems in M. mycoides subsp. capri encoding a (i) novel AAA-ATPase/subtilisin-like serine protease module, (ii) a putative AbiEii/AbiEi pair and (iii) a putative Fic/RelB pair. We sequence analyzed fourteen genomes of M. mycoides subsp. capri and confirmed the presence of at least one TA module in each of them. Interestingly, horizontal gene transfer signatures were also found in several genomic loci containing TA systems for several mycoplasma species. Transcriptomic and proteomic data confirmed differential expression profiles of these TA systems during mycoplasma growth in vitro. While the use of heterologous expression systems based on E. coli and B. subtilis showed clear limitations, the functionality and neutralization capacities of all three candidate TA systems were successfully confirmed using M. capricolum subsp. capricolum as a host. Additionally, M. capricolum subsp. capricolum was used to confirm the presence of functional TA system homologs in mycoplasmas of the Hominis and Pneumoniae phylogenetic groups. Finally, we showed that several of these M. mycoides subsp. capri toxins tested in this study, and particularly the subtilisin-like serine protease, could be used to establish a kill switch in mycoplasmas for industrial applications.
format	article
author	Virginia Hill Hatice Akarsu Rubén Sánchez Barbarroja Valentina L Cippà Peter Kuhnert Martin Heller Laurent Falquet Manfred Heller Michael H Stoffel Fabien Labroussaa Joerg Jores
author_facet	Virginia Hill Hatice Akarsu Rubén Sánchez Barbarroja Valentina L Cippà Peter Kuhnert Martin Heller Laurent Falquet Manfred Heller Michael H Stoffel Fabien Labroussaa Joerg Jores
author_sort	Virginia Hill
title	Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.
title_short	Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.
title_full	Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.
title_fullStr	Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.
title_full_unstemmed	Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.
title_sort	minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/cbe8f8f61d5b4ecf874e6a333c7b4b94
work_keys_str_mv	AT virginiahill minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT haticeakarsu minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT rubensanchezbarbarroja minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT valentinalcippa minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT peterkuhnert minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT martinheller minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT laurentfalquet minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT manfredheller minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT michaelhstoffel minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT fabienlabroussaa minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems AT joergjores minimalisticmycoplasmasharbordifferentfunctionaltoxinantitoxinsystems
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Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems.

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