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Tuberculosis Genomics and Transcriptomics: From Epidemiological to Evolutionary Aspects
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Tuberculosis Genomics and Transcriptomics: From Epidemiological to Evolutionary Aspects

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 13749

Special Issue Editors

Prof. Dr. Stefan Niemann

E-Mail Website
Guest Editor
Forschungszentrum Borstel - Zentrum fur Medizin und Biowissenschaften, Molecular and Experimental Mycobacteriology, Borstel, Germany
Interests: tuberculosis; genomics; transcriptomics
Dr. Iñaki Comas

E-Mail Website
Guest Editor
Biomedicine Institute of Valencia (IBV), Spanish Research Council (CSIC), C/ Jaume Roig, 11 46010 - València, Spain
Interests: tuberculosis; genomics; infectious diseases; microbial evolution and ecology; drug resistance; epidemiology

Special Issue Information

Dear Colleagues,

Combating tuberculosis (TB) is a major global health challenge, especially in developing countries, and bacteria of the Mycobacterium tuberculosis complex (Mtbc) remain key pathogens plaguing humanity. The emergence and spread of multidrug-resistant (MDR) Mtbc strains are particularly worrisome, culminating in half a million cases per year. Recently, numerous disruptions in medical services caused by COVID-19 worsened the picture, as exemplified by an increase in TB death indicated in the latest WHO report (WHO 2021).

The success of Mtbc strains is achieved by its peculiar life cycle, metabolism, and tropism for Homo sapiens. Major drivers that shape the adaptive landscape of these pathogens are the accumulation of resistance and compensatory mutations, leading progressively to Mtbc strains that can escape MDR therapy and transmit efficiently. Still, other mechanisms such as variations in the transcriptome, methylome, or metabolome that potentially drive virulence and host–pathogen interaction are not well defined, with nearly 30% of genes of the chromosome having unknown functions.

The growing availability of omics tools such as next-generation sequencing technologies allows for tracking the genetic bases of metabolisms and resistance mechanisms in single strains but also at population scales. Whole genome sequencing also allows to unravel unknown lineages: the evolution of the pathogen through time and space but also to detects chain transmission in the city and the hospital. Genome-wide association studies provide information on evolutionary and adaptive traits of microorganisms, and experimental evolution uncovers the possible modes of host change. At the revival period of Lamarckism, new insights might be obtained from transcriptomics and small RNA studies to decipher the path from genotype to phenotype.

This Special Issue intends to address those questions and to provide the scientific community with an overview of the recent developments and their future implications in the field of evolutionary genetics, molecular epidemiology, and metabolic pathways. Particular attention is paid to genomic and transcriptomic studies.

Prof. Dr. Stefan Niemann
Dr. Iñaki Comas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tuberculosis molecular epidemiology
  • genomics and transcriptomics
  • antibioresistance and compensatory mutations
  • metabolic pathways
  • experimental evolution
  • tuberculosis evolutionary history

Published Papers (4 papers)

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Research

6 pages, 616 KiB  
Article
Mycobacterium tuberculosis Genotypes and Drug Susceptibility Test Results from Timor-Leste: A Pilot Study
by Nevio Sarmento, Ella M. Meumann, Helder M. Pereira, Constantino Lopes, Maria Globan, Charlotte Hall, Matthew Di Palma, Nicole Hersch, Kristy Horan, Anna P. Ralph and Joshua R. Francis
Genes 2022, 13(10), 1733; https://doi.org/10.3390/genes13101733 - 27 Sep 2022
Cited by 1 | Viewed by 1916
Abstract
Tuberculosis (TB) is prevalent and a major public health problem in Timor-Leste. The government of Timor-Leste is prioritising the surveillance of TB and drug-susceptibility testing (DST) to understand the burden of TB and TB drug resistance in the country. Moreover, little is known [...] Read more.
Tuberculosis (TB) is prevalent and a major public health problem in Timor-Leste. The government of Timor-Leste is prioritising the surveillance of TB and drug-susceptibility testing (DST) to understand the burden of TB and TB drug resistance in the country. Moreover, little is known about the origin of Mycobacterium tuberculosis (MTB) in Timor-Leste. This study reports MTB DST and sequencing for Timor-Leste. A pilot study was carried out in which a convenience sample of TB isolates from mucopurulent sputum collected from presumptive TB patients in the capital Dili between July and December 2016 was tested for phenotypic and genotypic evidence of drug resistance. Standard MTB culture was performed at the Timor-Leste National Health Laboratory (NHL). The MTB isolates were sent to the Victorian Infectious Diseases Reference Laboratory (VIDRL) in Australia for DST and sequencing. Overall, 36 MTB isolates were detected at the NHL; 20 isolates were recovered during sub-culturing at VIDRL. All 20 isolates were susceptible to rifampicin, isoniazid, pyrazinamide, and ethambutol, with no genotypic markers of resistance identified. On sequencing, lineage 4 was the most common. The results of this study provide a small snapshot of MTB diversity and resistance in an under-sampled region with very high TB incidence. Future investment in whole-genome sequencing capacity in Timor-Leste will make it possible to undertake further, more representative analyses that may be used to evaluate transmission dynamics and epidemiology of genotypic markers of resistance. Full article
(This article belongs to the Special Issue Tuberculosis Genomics and Transcriptomics: From Epidemiological to Evolutionary Aspects)
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14 pages, 2120 KiB  
Article
Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3
by Yassir A. Shuaib, Christian Utpatel, Thomas A. Kohl, Ivan Barilar, Margo Diricks, Nadia Ashraf, Lothar H. Wieler, Glennah Kerubo, Eyob A. Mesfin, Awa Ba Diallo, Sahal Al-Hajoj, Perpetua Ndung’u, Margaret M. Fitzgibbon, Farzam Vaziri, Vitali Sintchenko, Elena Martinez, Sofia O. Viegas, Yang Zhou, Aya Azmy, Khaled Al-Amry, Sylvain Godreuil, Mandira Varma-Basil, Anshika Narang, Solomon Ali, Patrick Beckert, Viola Dreyer, Mwila Kabwe, Matthew Bates, Michael Hoelscher, Andrea Rachow, Andrea Gori, Emmanuel M. Tekwu, Larissa K. Sidze, Assam A. Jean-Paul, Veronique P. Beng, Francine Ntoumi, Matthias Frank, Aissatou Gaye Diallo, Souleymane Mboup, Belay Tessema, Dereje Beyene, Sadiq N. Khan, Roland Diel, Philip Supply, Florian P. Maurer, Harald Hoffmann, Stefan Niemann and Matthias Merkeradd Show full author list remove Hide full author list
Genes 2022, 13(6), 990; https://doi.org/10.3390/genes13060990 - 31 May 2022
Cited by 14 | Viewed by 4653
Abstract
Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over [...] Read more.
Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates. Full article
(This article belongs to the Special Issue Tuberculosis Genomics and Transcriptomics: From Epidemiological to Evolutionary Aspects)
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14 pages, 416 KiB  
Article
SNPs in Genes Related to DNA Damage Repair in Mycobacterium Tuberculosis: Their Association with Type 2 Diabetes Mellitus and Drug Resistance
by Damián E. Pérez-Martínez, Gustavo A. Bermúdez-Hernández, Carlos F. Madrazo-Moya, Irving Cancino-Muñoz, Hilda Montero, Cuauhtemoc Licona-Cassani, Raquel Muñiz-Salazar, Iñaki Comas and Roberto Zenteno-Cuevas
Genes 2022, 13(4), 609; https://doi.org/10.3390/genes13040609 - 29 Mar 2022
Cited by 3 | Viewed by 2439
Abstract
Genes related to DNA damage repair in Mycobacterium tuberculosis are critical for survival and genomic diversification. The aim of this study is to compare the presence of SNPs in genes related to DNA damage repair in sensitive and drug-resistant M. tuberculosis genomes isolated [...] Read more.
Genes related to DNA damage repair in Mycobacterium tuberculosis are critical for survival and genomic diversification. The aim of this study is to compare the presence of SNPs in genes related to DNA damage repair in sensitive and drug-resistant M. tuberculosis genomes isolated from patients with and without type 2 diabetes mellitus (T2DM). We collected 399 M. tuberculosis L4 genomes from several public repositories; 224 genomes belonging to hosts without T2DM, of which 123 (54.9%) had drug sensitive tuberculosis (TB) and 101 (45.1%) had drug resistance (DR)-TB; and 175 genomes from individuals with T2DM, of which 100 (57.1%) had drug sensitive TB and 75 (42.9%) had DR-TB. The presence of SNPs in the coding regions of 65 genes related to DNA damage repair was analyzed and compared with the resistance profile and the presence/absence of T2DM in the host. The results show the phylogenetic relationships of some SNPS and L4 sub-lineages, as well as differences in the distribution of SNPs present in DNA damage repair-related genes related to the resistance profile of the infecting strain and the presence of T2DM in the host. Given these differences, it was possible to generate two discriminant functions to distinguish between drug sensitive and drug resistant genomes, as well as patients with or without T2DM. Full article
(This article belongs to the Special Issue Tuberculosis Genomics and Transcriptomics: From Epidemiological to Evolutionary Aspects)
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15 pages, 2168 KiB  
Article
Molecular Epidemiology of Mycobacterium tuberculosis Complex Strains in Urban and Slum Settings of Nairobi, Kenya
by Glennah Kerubo, Perpetua Ndungu, Yassir Adam Shuaib, Evans Amukoye, Gunturu Revathi, Susanne Homolka, Samuel Kariuki, Matthias Merker and Stefan Niemann
Genes 2022, 13(3), 475; https://doi.org/10.3390/genes13030475 - 8 Mar 2022
Cited by 4 | Viewed by 3892
Abstract
Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of [...] Read more.
Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients’ demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1–L4). The two dominating lineages were L4 with 55.8% (n = 215) and L3 with 25.7% (n = 99) of all strains, respectively. Genome-based cluster analysis showed that 30.4% (117/385) of the strains were clustered using a ≤5 single-nucleotide polymorphism (SNP) threshold as a surrogate marker for direct patient-to-patient MTBC transmission. Moreover, 5.2% (20/385) of the strains were multidrug-resistant (MDR), and 50.0% (n = 10) were part of a genome-based cluster (i.e., direct MDR MTBC transmission). Notably, 30.0% (6/20) of the MDR strains were resistant to all first-line drugs and are part of one molecular cluster. Moreover, TB patients in urban living setting had 3.8 times the odds of being infected with a drug-resistant strain as compared to patients from slums (p-value = 0.002). Our results show that L4 strains are the main causative agent of TB in Nairobi and MDR strain transmission is an emerging concern in urban settings. This emphasizes the need for more focused infection control measures and contact tracing of patients with MDR TB to break the transmission chains. Full article
(This article belongs to the Special Issue Tuberculosis Genomics and Transcriptomics: From Epidemiological to Evolutionary Aspects)
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