Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system

Jose Maria Urtasun-Elizari; Ruoyao Ma; Hayleah Pickford; Damien Farrell; Gabriel Gonzalez; Viktor Perets; Chie Nakajima; Yasuhiko Suzuki; David E. MacHugh; Apoorva Bhatt; Stephen V. Gordon

doi:10.1016/j.tube.2024.102544

Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system

Jose Maria Urtasun-Elizari, Ruoyao Ma, Hayleah Pickford, Damien Farrell, Gabriel Gonzalez, Viktor Perets, Chie Nakajima, Yasuhiko Suzuki, David E. MacHugh, Apoorva Bhatt, Stephen V. Gordon^*

^*Corresponding author for this work

Computer Science

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional. We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.

Original language	English
Article number	102544
Pages (from-to)	1-8
Number of pages	8
Journal	Tuberculosis
Volume	148
Early online date	14 Jul 2024
DOIs	https://doi.org/10.1016/j.tube.2024.102544
Publication status	Published - Sept 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

This study was supported by Science Foundation Ireland (SFI) Investigator Programme SFI/15/IA/3154 (DEM and SVG); a Biotechnology and Biological Sciences Research Council (BBSRC, UK) award BB/N004574/1 (AB and SVG); and the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP23jm0110021, JP23wm0125008 and JP233fa627005 (YS and CN). Funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.

Funders	Funder number
Japan Agency for Medical Research and Development
Science Foundation Ireland	SFI/15/IA/3154
Biotechnology and Biological Sciences Research Council	BB/N004574/1
AMED	JP23jm0110021, JP23wm0125008, JP233fa627005

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title = "Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system",

abstract = "The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional. We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.",

author = "Urtasun-Elizari, {Jose Maria} and Ruoyao Ma and Hayleah Pickford and Damien Farrell and Gabriel Gonzalez and Viktor Perets and Chie Nakajima and Yasuhiko Suzuki and MacHugh, {David E.} and Apoorva Bhatt and Gordon, {Stephen V.}",

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doi = "10.1016/j.tube.2024.102544",

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AU - Urtasun-Elizari, Jose Maria

AU - Ma, Ruoyao

AU - Pickford, Hayleah

AU - Farrell, Damien

AU - Gonzalez, Gabriel

AU - Perets, Viktor

AU - Nakajima, Chie

AU - Suzuki, Yasuhiko

AU - MacHugh, David E.

AU - Bhatt, Apoorva

AU - Gordon, Stephen V.

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AB - The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional. We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.

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Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system

Abstract

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