The MtZ Strain: Molecular Characteristics and Outbreak Investigation of the Most Successful Mycobacterium tuberculosis Strain in Aragon Using Whole-Genome Sequencing

Comín, Jéssica; Madacki, Jan; Rabanaque, Isabel; Antón, María Zúñiga; Ibarz, Daniel; Cebollada, A.; Viñuelas, Jesús; Torres, Luís; Sahagún, Juan; Klopp, Christophe; Gonzalo-Asensio, Jesús; Brosch, Roland; Iglesias, M. Bártulos; Samper, Sofía

doi:10.3389/fcimb.2022.887134

Cited by 4 publications

(6 citation statements)

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“…One important fact in MtZ strain is the inactivation of desA3 gene due to an IS 6110 insertion (point 3606308 in H37Rv genome) ( 3 , 4 ). desA3 encodes a stearoyl-CoA Δ9 desaturase that produces oleic acid, a precursor for mycobacterial membrane phospholipids and triglycerides ( 39 ) and considered essential ( 40 ) because it is the only enzyme with this activity described in M. tuberculosis ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…MtZ belongs to the modern lineage L4.10, with an undefined spoligotype (SIT-773) and 12 IS 6110 . Previous analyses of this strain detected eight SNPs in genes considered as virulence factors, as well as an increase in the secretion of PE_PGRS family proteins ( 4 ). Absence of secretion of these factors has been related with an increase in virulence in the Beijing family ( 5 ), but how oversecretion, as observed in MtZ, affects virulence remains unknown.…”

Section: Introductionmentioning

confidence: 94%

“…The largest outbreak in Aragon was caused by a strain called Mycobacterium tuberculosis Zaragoza (MtZ), described in previous works ( 2 – 4 ). The outbreak started in the 90s and continues today, with more than 240 cases reported to date and representing around 10% of the total cases in our community.…”

Section: Introductionmentioning

confidence: 99%

“…Absence of secretion of these factors has been related with an increase in virulence in the Beijing family ( 5 ), but how oversecretion, as observed in MtZ, affects virulence remains unknown. Furthermore, we carried out the transcriptomic study using three MtZ isolates that differed in the location of an IS 6110 copy in order to identify differences in the expression of the adjacent genes next to IS 6110 , where no significant differences were detected ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic profile of the most successful Mycobacterium tuberculosis strain in Aragon, the MtZ strain, during exponential and stationary growth phases

Comín,

Campos,

Gonzalo-Asensio

et al. 2023

Microbiol Spectr

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The Mycobacterium tuberculosis Zaragoza (MtZ) strain has produced the largest outbreak in Aragon Community, Spain, as it started in the 90s and continues today, contributing with more than 240 cases of tuberculosis, around 10% of the TB cases. Previous studies were carried out to identify the reasons for its successful spread capacity among the population. Some single nucleotide polymorphisms (SNPs) in genes considered as virulence factors were found, as well as an oversecretion of PE_PGRS factors. Different copies of IS 6110 have been localized, and a transcriptomic study was carried out to study how the different IS 6110 copies could affect the adjacent gene expression. In this work, we analyzed the transcriptomic profile of the MtZ, strain trying to delve into the mechanisms behind its success. We found that ESX-1 system is upregulated during both exponential and stationary growth phases in vitro , as well as the virulence pathways of cholesterol degradation and peptidoglycan biosynthesis. In addition, MtZ has the iron uptake genes downregulated in exponential growth phase (mycobactin biosynthesis and IrtAB transporters), while the iron storage could be upregulated. The desA3 gene transcription was interrupted by the insertion of an IS 6110 copy. This gene codes for a stearoyl-coenzyme A (CoA) Δ9 desaturase involved in the production of oleic acid, which is necessary for the metabolism of the bacteria. In spite of this, although MtZ strain has an initial long lag phase growing in liquid media, it is capable of achieving normal growth, suggesting the existence of an alternative route for obtaining oleic acid. IMPORTANCE Aragon Community suffered, during the first years of the beginning of this century, a large outbreak caused by the MtZ strain, producing more than 240 cases to date. MtZ strain and the outbreak have been previously studied from an epidemiological and molecular point of view. In this work, we analyzed the transcriptomic profile of the strain for better understanding of its success among our population. We have discovered that MtZ has some upregulated virulence pathways, such as the ESX-1 system, the cholesterol degradation pathway or the peptidoglycan biosynthesis. Interestingly, MtZ has downregulated the uptake of iron. Another special feature of MtZ strain is the interruption of desA3 gene, essential for producing oleic acid. Although the strain takes a long time to grow in the initial culture media, eventually it is able to reach normal optical densities, suggestive of the presence of another route for obtaining oleic acid in Mycobacterium tuberculosis .

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptomic profile of the most successful Mycobacterium tuberculosis strain in Aragon, the MtZ strain, during exponential and stationary growth phases

Comín,

Campos,

Gonzalo-Asensio

et al. 2023

Microbiol Spectr

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“…More than 10 million cases are confirmed per year. Other than COVID-19, TB is the second leading cause of death due to infectious disease (2,3). TB remains a major public health concern, particularly in developing countries, and indeed it cannot be ignored or underestimated.…”

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confidence: 99%

Devising novel near-infrared aggregation-induced-emission luminogen labeling for point-of-care diagnosis of <i>Mycobacterium tuberculosis </i>

Griffiths

Zhao

Song

et al. 2023

BST

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Detecting and appropriately diagnosing a Mycobacterium tuberculosis infection remains technologically difficult because the pathogen commonly hides in macrophages in a dormant state. Described here is novel near-infrared aggregation-induced-emission luminogen (AIEgen) labeling developed by the current authors' laboratory for point-of-care (POC) diagnosis of an M. tuberculosis infection. The selectivity of AIEgen labeling, the labeling of intracellular M. tuberculosis by AIEgen, and the labeling of M. tuberculosis in sputum samples by AIEgen, along with its accuracy, sensitivity, and specificity, were preliminarily evaluated. Results indicated that this near-infrared AIEgen labeling had satisfactory selectivity and it labeled intracellular M. tuberculosis and M. tuberculosis in sputum samples. It had a satisfactory accuracy (95.7%), sensitivity (95.5%), and specificity (100%) for diagnosis of an M. tuberculosis infection in sputum samples. The current results indicated that near-infrared AIEgen labeling might be a promising novel diagnostic tool for POC diagnosis of M. tuberculosis infection, though further rigorous verification of these findings is required.

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Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes

Comín

Cebollada

Ibarz

et al. 2022

Sci Rep

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The incidence of tuberculosis in Aragon, Spain, is around ten cases per 100,000 inhabitants. Since 2004, a molecular surveillance protocol has been carried out; therefore, all M. tuberculosis strains are genotyped. Recently, whole-genome sequencing has been implemented for relevant isolates. The aim of this work is to characterise at the molecular level the causative strains of the 26 largest outbreaks of the community (including ten or more cases), genotyped by IS6110-RFLP and causing 26% of tuberculosis cases. To achieve this objective, two or three isolates of each IS6110-cluster belonging to different years were selected for sequencing. We found that strains of lineages L4.8, L4.3 and L4.1.2 were the most frequent. The threshold of 12 SNPs as the maximum distance for confirming the belonging to an outbreak was met for 18 of the 26 IS6110-clusters. Four pairs of isolates with more than 90 SNPs were identified as not belonging to the same strain, and four other pairs were kept in doubt as the number of SNPs was close to 12, between 14 and 35. The study of Regions of Difference revealed that they are lineage conserved. Moreover, we could analyse the IS6110 locations for all genome-sequenced isolates, finding some frequent locations in isolates belonging to the same lineage and certain IS6110 movements between the paired isolates. In the vast majority, these movements were not captured by the IS6110-RFLP pattern. After classifying the genes containing SNP by their functional category, we could confirm that the number of SNPs detected in genes considered as virulence factors and the number of cases the strain produced were not related, suggesting that a particular SNP is more relevant than the number. The characteristics found in the most successful strains in our community could be useful for other researchers in epidemiology, virulence and pathogenesis.

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The MtZ Strain: Molecular Characteristics and Outbreak Investigation of the Most Successful Mycobacterium tuberculosis Strain in Aragon Using Whole-Genome Sequencing

Cited by 4 publications

References 61 publications

Transcriptomic profile of the most successful Mycobacterium tuberculosis strain in Aragon, the MtZ strain, during exponential and stationary growth phases

Transcriptomic profile of the most successful Mycobacterium tuberculosis strain in Aragon, the MtZ strain, during exponential and stationary growth phases

Devising novel near-infrared aggregation-induced-emission luminogen labeling for point-of-care diagnosis of <i>Mycobacterium tuberculosis </i>

Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes

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