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Natural mutations in the sensor kinase of the PhoPR two-component regulatory system modulate virulence of ancestor-like tuberculosis bacilli

ABSTRACT: Natural mutations in the sensor kinase of the PhoPR two-component regulatory system modulate virulence of ancestor-like tuberculosis bacilli

PROVIDER: PRJNA955279 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24163400.fastq.gz	Fastqsanger.gz
	SRR24163401.fastq.gz	Fastqsanger.gz
	SRR24163402.fastq.gz	Fastqsanger.gz
	SRR24163403.fastq.gz	Fastqsanger.gz
	SRR24163404.fastq.gz	Fastqsanger.gz

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Similar Datasets

Natural mutations in the sensor kinase of the PhoPR two-component regulatory system modulate virulence of ancestor-like tuberculosis bacilli

Project description:In Mycobacterium tuberculosis, the PhoPR two-component regulatory system controls production and secretion of proteins and lipid virulence effectors. Several mutations, present in phoR of Mycobacterium canettii relative to M. tuberculosis, impact the expression of the PhoP regulon and the pathogenicity of the strains. Here, we analyse by RNA-seq the expression profile of PhoP-regulated genes between the two M. tuberculosis strains H37Rv and HN878 and the two M. canettii isolates STB-Ks and STB-Kr.

2023-05-24 | GSE229680 | GEO

Natural mutations in the sensor kinase of the PhoPR two-component regulatory system modulate virulence of ancestor-like tuberculosis bacilli.

Project description:The molecular factors and genetic adaptations that contributed to the emergence of Mycobacterium tuberculosis (MTB) from an environmental Mycobacterium canettii-like ancestor, remain poorly investigated. In MTB, the PhoPR two-component regulatory system controls production and secretion of proteins and lipid virulence effectors. Here, we describe that several mutations, present in phoR of M. canettii relative to MTB, impact the expression of the PhoP regulon and the pathogenicity of the strains. First, we establish a molecular model of PhoR and show that some substitutions found in PhoR of M. canettii are likely to impact the structure and activity of this protein. Second, we show that STB-K, the most attenuated available M. canettii strain, displays lower expression of PhoP-induced genes than MTB. Third, we demonstrate that genetic swapping of the phoPR allele from STB-K with the ortholog from MTB H37Rv enhances expression of PhoP-controlled functions and the capacities of the recombinant strain to colonize human macrophages, the MTB target cells, as well as to cause disease in several mouse infection models. Fourth, we extended these observations to other M. canettii strains and confirm that PhoP-controlled functions are expressed at lower levels in most M. canettii strains than in M. tuberculosis. Our findings suggest that distinct PhoR variants have been selected during the evolution of tuberculosis bacilli, contributing to higher pathogenicity and persistence of MTB in the mammalian host.

| S-EPMC10348564 | biostudies-literature

Bacilli

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Bacilli bacterium

Project description:Bacilli bacterium overview

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Evolutionary conserved mutations in PhoPR attenuate the virulence of animal-adapted tuberculosis strains for humans

2014-07-07 | GSE54421 | GEO

Gram negative bacilli

Project description:Gram negative bacilli Genome sequencing

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Ralstonia solanacearum strain:Ancestor

Project description:Ralstonia solanacearum strain:Ancestor Genome sequencing

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Evolutionary conserved mutations in PhoPR attenuate the virulence of animal-adapted tuberculosis strains for humans

Project description:By genome comparison of 30 MTBC strains, we identified three SNPs affecting the phoPR genes of members of the animal and M. africanum lineages that were not seen in the M. tuberculosis sensu-stricto genomes. The genes phoPR encode a two component regulatory system that is known for its strong impact on virulence and immunogenicity of M. tuberculosis due to its key role in the regulation of genes involved in lipid synthesis and secretion of the 6 kDa secreted antigenic target ESAT-6. To explore whether these SNPs affect the expression of the PhoP regulon, we compared the transcriptome of M. tuberculosis mutants lacking the endogenous phoPR genes (M-NM-^TphoPR) and their complemented derivatives expressing either the M. bovis or M. tuberculosis allele of phoPR (phoPR-bovis and phoPR-TB respectively). These comparisons were performed in parallel in two M. tuberculosis strains from distinct genetic backgrounds, i.e. strain GC1237 from lineage 2 (also named East-Asia or Beijing cluster) and the H37Rv reference strain from lineage 4 (also named Euro-American cluster). To perform the transcriptomic comparison of the different M. tuberculosis variants (M-NM-^TphoPR, complemented and wt) from the two distinct genetic background, a customized micro-array has been designed then manufactured by Agilent (8 x 15k format). The design of oligonucleotides covering all protein coding sequences was done using OligoArray version 2.1 on the basis of the 3924 predicted coding sequences composing the entire M. tuberculosis H37Rv reference genome. The experimental data for each of the comparison consisted of 4 hybridizations (2 biological replicates with dye-swap); 16 in the end for each genetic background.

2014-07-07 | E-GEOD-54421 | biostudies-arrayexpress

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