Diversity of Mycobacterium tuberculosis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 11902

Special Issue Editors


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Guest Editor
Lab. Of Ecology, Systematics and Evolution, Université Paris-Saclay, Plateau de Saclay, France
Interests: tuberculosis; evolution; host pathogen interactions; CRISPR; data-mining

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Co-Guest Editor
Centre International de Recherche en Infectiology (CIRI), Lyon University Hospital, Lyon, France
Interests: tuberculosis; micro-diversity; adaptation; host-pathogen interaction; clinical presentation

Special Issue Information

Dear Colleagues,

Although it has gained less attention than COVID-19, tuberculosis (TB) caused by the Mycobacterium tuberculosis (Mtb) complex remains among the most prevalent and deadly infectious diseases worldwide. Infections result in diverse clinical outcomes, from latent asymptomatic infection to pulmonary or extrapulmonary manifestations of disease, with an array of severity symptoms. The origin of the diversity of these clinical presentations remains poorly understood.

Mtb was long considered a functionally monomorphic bacterium, and its diverse clinical outcomes were attributed to host characteristics and/or environment. With the advent of Whole Genome Sequencing, the attainable diversity expanded, from SNPs distinguishing the same strain inside an epidemic event, to diversity inside a clinical sample. Relating this unexpected diversity to clinical characteristics is, however, a particularly difficult task. Indeed, the bacterium is strictly clonal, with no horizontal gene transfer, which critically lowers the power of standard population genetics approaches.

Nevertheless, association studies—in vitro and ex vivo studies—begin to shed light on the functional impact of this diversity. As Co-Guest Editors of this Special Issue, we invite you to submit research articles, review articles, and short communications related to the diversity, microdiversity, and adaptation of the Mycobacterium tuberculosis complex. Reviews should focus on present knowledge on the current diversity of Mtb and its functional consequences. Research articles and short communications may present new exploratory studies or new methods to unravel microdiversity, mechanisms that control diversification, and/or relate diversity to clinical or geographical features of the bacillus.

Dr. Guislaine Réfrégier
Dr. Charlotte Genestet
Guest Editors

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Keywords

  • Mycobacterium tuberculosis
  • diversity
  • micro-diversity
  • Next Generation Sequencing
  • adaptation
  • clinical presentation
  • epidemiology

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Published Papers (5 papers)

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Editorial

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3 pages, 204 KiB  
Editorial
Mycobacterium tuberculosis Diversity Exploration: A Way to Serve the Three Main Weapons against Epidemics, Hygiene, Vaccine Development and Chemotherapy
by Guislaine Refrégier and Charlotte Genestet
Microorganisms 2022, 10(8), 1492; https://doi.org/10.3390/microorganisms10081492 - 25 Jul 2022
Viewed by 1210
Abstract
As highlighted by the SARS pandemic which is still ongoing, the battle against pathogens relies on three main “weapons”: hygiene, vaccine development and chemotherapy strategies [...] Full article
(This article belongs to the Special Issue Diversity of Mycobacterium tuberculosis)

Research

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14 pages, 1157 KiB  
Article
Genetic Diversity and Primary Drug Resistance of Mycobacterium tuberculosis Beijing Genotype Strains in Northwestern Russia
by Anna Vyazovaya, Alena Gerasimova, Regina Mudarisova, Daria Terentieva, Natalia Solovieva, Viacheslav Zhuravlev and Igor Mokrousov
Microorganisms 2023, 11(2), 255; https://doi.org/10.3390/microorganisms11020255 - 19 Jan 2023
Cited by 9 | Viewed by 1853
Abstract
The Beijing genotype is the main family of Mycobacterium tuberculosis in Russia. We analyzed its diversity and drug resistance in provinces across Northwestern Russia to identify the epidemiologically relevant Beijing strains. The study collection included 497 isolates from newly-diagnosed tuberculosis (TB) patients. Bacterial [...] Read more.
The Beijing genotype is the main family of Mycobacterium tuberculosis in Russia. We analyzed its diversity and drug resistance in provinces across Northwestern Russia to identify the epidemiologically relevant Beijing strains. The study collection included 497 isolates from newly-diagnosed tuberculosis (TB) patients. Bacterial isolates were subjected to drug-susceptibility testing and genotyping. The Beijing genotype was detected in 57.5% (286/497); 50% of the Beijing strains were multidrug-resistant (MDR). Central Asian/Russian and B0/W148 groups included 176 and 77 isolates, respectively. MDR was more frequent among B0/W148 strains compared to Central Asian/Russian strains (85.7% vs. 40.3%, p < 0.0001). Typing of 24 minisatellite loci of Beijing strains revealed 82 profiles; 230 isolates were in 23 clusters. The largest Central Asian/Russian types were 94-32 (n = 75), 1065-32 (n = 17), and 95-32 (n = 12). B0/W148 types were 100-32 (n = 59) and 4737-32 (n = 5). MDR was more frequent in types 1065-32 (88.2%), 100-32 (83.1%), and 4737-32 (100%). In contrast, type 9391-32 (n = 9) included only drug-susceptible strains. To conclude, M. tuberculosis Beijing genotype is dominant in Northwestern Russia, and an active transmission of overwhelmingly MDR B0/W148 types explains the reported increase of MDR-TB. The presence of MDR-associated minor variants (type 1071-32/ancient Beijing and Central Asia Outbreak strain) in some of the studied provinces also requires attention. Full article
(This article belongs to the Special Issue Diversity of Mycobacterium tuberculosis)
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15 pages, 2886 KiB  
Article
Features of Mycobacterium bovis Complete Genomes Belonging to 5 Different Lineages
by Ciriac Charles, Cyril Conde, Fabien Vorimore, Thierry Cochard, Lorraine Michelet, Maria Laura Boschiroli and Franck Biet
Microorganisms 2023, 11(1), 177; https://doi.org/10.3390/microorganisms11010177 - 11 Jan 2023
Cited by 4 | Viewed by 3095
Abstract
Mammalian tuberculosis (TB) is a zoonotic disease mainly due to Mycobacterium bovis (M. bovis). A current challenge for its eradication is understanding its transmission within multi-host systems. Improvements in long-read sequencing technologies have made it possible to obtain complete bacterial genomes [...] Read more.
Mammalian tuberculosis (TB) is a zoonotic disease mainly due to Mycobacterium bovis (M. bovis). A current challenge for its eradication is understanding its transmission within multi-host systems. Improvements in long-read sequencing technologies have made it possible to obtain complete bacterial genomes that provide a comprehensive view of species-specific genomic features. In the context of TB, new genomic references based on complete genomes genetically close to field strains are also essential to perform precise field molecular epidemiological studies. A total of 10 M. bovis strains representing each genetic lineage identified in France and in other countries were selected for performing complete assembly of their genomes. Pangenome analysis revealed a “closed” pangenome composed of 3900 core genes and only 96 accessory genes. Whole genomes-based alignment using progressive Mauve showed remarkable conservation of the genomic synteny except that the genomes have a variable number of copies of IS6110. Characteristic genomic traits of each lineage were identified through the discovery of specific indels. Altogether, these results provide new genetic features that improve the description of M. bovis lineages. The availability of new complete representative genomes of M. bovis will be useful to epidemiological studies and better understand the transmission of this clonal-evolving pathogen. Full article
(This article belongs to the Special Issue Diversity of Mycobacterium tuberculosis)
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10 pages, 1437 KiB  
Article
Genomic Diversity of the Rarely Observed Genotype of the Mycobacterium tuberculosis Central Asian (CAS) Lineage 3 from North Brazil
by Emilyn Costa Conceição, Marília Lima da Conceição, Davi Josué Marcon, Johannes Loubser, Gabrielly Leite Andrade, Sandro Patroca da Silva, Ana Cecília Ribeiro Cruz, Abhinav Sharma, Philip Suffys and Karla Valéria Batista Lima
Microorganisms 2023, 11(1), 132; https://doi.org/10.3390/microorganisms11010132 - 4 Jan 2023
Cited by 1 | Viewed by 2806
Abstract
Mycobacterium tuberculosis (Mtb) Central Asian Strain (CAS) Lineage 3 (L3) genotype is predominantly found in East-Africa, Central-Asia, Western-Asia, and South-Asia; however, a new spoligotyping CAS/SIT2545 was found in northern regions of Brazil. We aimed to characterize and describe the genetic diversity [...] Read more.
Mycobacterium tuberculosis (Mtb) Central Asian Strain (CAS) Lineage 3 (L3) genotype is predominantly found in East-Africa, Central-Asia, Western-Asia, and South-Asia; however, a new spoligotyping CAS/SIT2545 was found in northern regions of Brazil. We aimed to characterize and describe the genetic diversity and perform a phylogenetic assessment of this novel genotype. We performed 24-MIRU-VNTR loci and Whole-genome sequencing (WGS) of six Brazilian isolates previously spoligotyped. The libraries were prepared using a Nextera-XT kit and sequenced in a NextSeq 550 Illumina instrument. We performed lineage assignment and genomic characterization. From publicly available genomes of Mtb L3 and other lineages, we created a robust dataset to run the MTBSeq pipeline and perform a phylogenetic analysis. MIRU-VNTR and WGS confirmed CAS/SIT2545 belongs to L3. Out of 1691 genomes, 1350 (79.83%) passed in quality control (genomic coverage > 95%). Strain 431 differed in 52 single nucleotide variants (SNV), confirming it does not belong to the same transmission chain. The eight genomes from a global dataset clustered closer to Brazilian strains differed in >52 SNVs. We hypothesized L3 and L1 were introduced in Brazilian Northern in the same historical event; however, there is a need for additional studies exploring the genetic diversity of Mtb Brazilian Northern. Full article
(This article belongs to the Special Issue Diversity of Mycobacterium tuberculosis)
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12 pages, 2061 KiB  
Article
Use of Whole-Genome Sequencing to Explore Mycobacterium tuberculosis Complex Circulating in a Hotspot Department in France
by Typhaine Billard-Pomares, Julie Marin, Pauline Quagliaro, Frédéric Méchaï, Violaine Walewski, Samira Dziri and Etienne Carbonnelle
Microorganisms 2022, 10(8), 1586; https://doi.org/10.3390/microorganisms10081586 - 6 Aug 2022
Cited by 3 | Viewed by 2076
Abstract
The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients [...] Read more.
The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs. Full article
(This article belongs to the Special Issue Diversity of Mycobacterium tuberculosis)
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