Biological and Epidemiological Consequences of MTBC Diversity.

Published on Jan 1, 2017in Advances in Experimental Medicine and Biology2.126
· DOI :10.1007/978-3-319-64371-7_5
Mireia Coscolla25
Estimated H-index: 25
(Swiss TPH: Swiss Tropical and Public Health Institute)
Tuberculosis is caused by different groups of bacteria belonging to the Mycobacterium tuberculosis complex (MTBC). The combined action of human factors, environmental conditions and bacterial virulence determine the extent and form of human disease. MTBC virulence is a composite of different clinical phenotypes such as transmission rate and disease severity among others. Clinical phenotypes are also influenced by cellular and immunological phenotypes. MTBC phenotypes are determined by the genotype, therefore finding genotypes responsible for clinical phenotypes would allow discovering MTBC virulence factors. Different MTBC strains display different cellular and clinical phenotypes. Strains from Lineage 5 and Lineage 6 are metabolically different, grow slower, and are less virulent. Also, at least certain groups of Lineage 2 and Lineage 4 strains are more virulent in terms of disease severity and human-to-human transmission. Because phenotypic differences are ultimately caused by genotypic differences, different genomic loci have been related to various cellular and clinical phenotypes. However, defining the impact of specific bacterial genomic loci on virulence when other bacterial determinants, human and environmental factors are also impacting the phenotype would contribute to a better knowledge of tuberculosis virulence and ultimately benefit tuberculosis control.
  • References (199)
  • Citations (7)
📖 Papers frequently viewed together
5 Citations
59 Citations
42 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
Abstract Mycobacterium tuberculosis is an adaptable intracellular pathogen, existing in both dormant as well as active disease-causing states. Here, we report systematic proteomic analyses of four strains, H37Ra, H37Rv, and clinical isolates BND and JAL, to determine the differences in protein expression patterns that contribute to their virulence and drug resistance. Resolution of lysates of the four strains by liquid chromatography, coupled to mass spectrometry analysis, identified a total of ...
17 CitationsSource
#1Lingxiang Zhu (Beijing Institute of Genomics)H-Index: 2
#2Jun Zhong (Beijing Institute of Genomics)H-Index: 5
Last. Fei Chen (Beijing Institute of Genomics)H-Index: 16
view all 20 authors...
Tuberculosis (TB) remains one of the most common infectious diseases caused by Mycobacterium tuberculosis complex (MTBC). To panoramically analyze MTBC's genomic methylation, we completed the genomes of 12 MTBC strains (Mycobacterium bovis; M. bovis BCG; M. microti; M. africanum; M. tuberculosis H37Rv; H37Ra; and 6 M. tuberculosis clinical isolates) belonging to different lineages and characterized their methylomes using single-molecule real-time (SMRT) technology. We identified three (m6)A sequ...
35 CitationsSource
#1Anita H. Melnyk (U of O: University of Ottawa)H-Index: 4
#2Alex Wong (Carleton University)H-Index: 27
Last. Rees Kassen (U of O: University of Ottawa)H-Index: 30
view all 3 authors...
Antibiotic resistance is increasing in pathogenic microbial populations and is thus a major threat to public health. The fate of a resistance mutation in pathogen populations is determined in part by its fitness. Mutations that suffer little or no fitness cost are more likely to persist in the absence of antibiotic treatment. In this review, we performed a meta-analysis to investigate the fitness costs associated with single mutational events that confer resistance. Generally, these mutations we...
172 CitationsSource
#1Mireia Coscolla (University of Basel)H-Index: 25
#2Sebastien Gagneux (University of Basel)H-Index: 58
The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically ...
147 CitationsSource
#1Damien Portevin (University of Basel)H-Index: 9
#2Sudarkodi Sukumar (NUS: National University of Singapore)H-Index: 1
Last. Markus R. WenkH-Index: 71
view all 10 authors...
Mycolic acids (MAs) are α-alkyl, β-hydroxy long-chain fatty acids found in abundance in the cell envelope of the Mycobacterium tuberculosis complex (MTBC). MAs form an efficient permeability barrier, modulate host innate immune responses, and are the targets of several anti-tuberculosis drugs. Using mass spectrometry, we measured the relative abundance of 80 MA species across 36 clinical isolates of MTBC covering four major phylogenetic lineages. We found significant variations in the MA pattern...
21 CitationsSource
#1Kirsten I. BosH-Index: 21
#2Kelly M. Harkins (ASU: Arizona State University)H-Index: 5
Last. Johannes Krause (MPG: Max Planck Society)H-Index: 58
view all 28 authors...
Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact1. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World2. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch3, although this has yet t...
209 CitationsSource
#1Jesús Gonzalo-Asensio (University of Zaragoza)H-Index: 15
#2Wladimir Malaga (Paul Sabatier University)H-Index: 17
Last. Christophe Guilhot (Paul Sabatier University)H-Index: 33
view all 11 authors...
Although the bovine tuberculosis (TB) agent, Mycobacterium bovis, may infect humans and cause disease, long-term epidemiological data indicate that humans represent a spill-over host in which infection with M. bovis is not self-maintaining. Indeed, human-to-human transmission of M. bovis strains and other members of the animal lineage of the tubercle bacilli is very rare. Here, we report on three mutations affecting the two-component virulence regulation system PhoP/PhoR (PhoPR) in M. bovis and ...
93 CitationsSource
#1Ruth Stavrum (University of Bergen)H-Index: 10
#2George PrayGod (NIMR: National Institute for Medical Research)H-Index: 17
Last. Harleen M. S. Grewal (University of Bergen)H-Index: 23
view all 12 authors...
Background There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different li...
11 CitationsSource
#1Leopold D. Tientcheu (Medical Research Council)H-Index: 8
#2Jayne S. Sutherland (Medical Research Council)H-Index: 26
Last. Martin O. C. Ota (Medical Research Council)H-Index: 35
view all 9 authors...
In The Gambia, Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum (Maf) are major causes of tuberculosis (TB). Maf is more likely to cause TB in immune suppressed individuals, implying differences in virulence. Despite this, few studies have assessed the underlying immunity to the two pathogens in human. In this study, we analyzed T-cell responses from 19 Maf- and 29 Mtb-infected HIV-negative patients before and after TB chemotherapy following overnight stimulation of whole blood with ...
16 CitationsSource
#1Yih-Yuan Chen (NIH: National Institutes of Health)H-Index: 10
#2Jia-Ru Chang (NIH: National Institutes of Health)H-Index: 8
Last. Horng-Yunn Dou (NIH: National Institutes of Health)H-Index: 11
view all 7 authors...
It is unclear to what extent the host-responses elicited by Beijing versus non-Beijing strains of Mycobacterium tuberculosis (MTB) contribute to the predominance of modern Beijing strains in Taiwan and some other Asian countries. The purpose of this study was to compare the expression profiles of virulence-related genes in human monocyte-derived macrophages infected in vitro with Beijing (ancient and modern strains) and non-Beijing strains (EAI strains) of MTB that are epidemic in Taiwan. We fou...
24 CitationsSource
Cited By7
#1James M. Trauer (Monash University)H-Index: 13
#2Peter J. Dodd (University of Sheffield)H-Index: 17
Last. David W. Dowdy (Johns Hopkins University)H-Index: 40
view all 11 authors...
Although less well-recognised than for other infectious diseases, heterogeneity is a defining feature of TB epidemiology. To advance toward TB elimination, this heterogeneity must be better understood and addressed. Drivers of heterogeneity in TB epidemiology act at the level of the infectious host, organism, susceptible host, environment and distal determinants. These effects may be amplified by social mixing patterns, while the variable latent period between infection and disease may mask hete...
4 CitationsSource
#1Liliana K. Rutaihwa (University of Basel)H-Index: 3
#2Mohamed Sasamalo (University of Basel)H-Index: 9
Last. Sebastien Gagneux (University of Basel)H-Index: 58
view all 18 authors...
BACKGROUND Human tuberculosis (TB) is caused by seven phylogenetic lineages of the Mycobacterium tuberculosis complex (MTBC), Lineage 1-7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, strain variation in the MTBC influences the outco...
1 CitationsSource
#1Sonia BorrellH-Index: 22
#2Andrej TraunerH-Index: 13
Last. Sebastien GagneuxH-Index: 58
view all 14 authors...
The Mycobacterium tuberculosis complex (MTBC) causes tuberculosis (TB) in humans and various other mammals. The human-adapted members of the MTBC comprise seven phylogenetic lineages that differ in their geographical distribution. There is growing evidence that this phylogeographic diversity modulates the outcome of TB infection and disease. For decades, TB research and development has focused on the two canonical MTBC laboratory strains H37Rv and Erdman, both of which belong to Lineage 4. Relyi...
13 CitationsSource
#1Marc WoodmanH-Index: 1
#2Ilsa L. HaeuslerH-Index: 1
view all 3 authors...
There are an estimated 10 million new cases of tuberculosis worldwide annually, with 282,000 new or relapsed cases each year reported from the Americas. With improvements in genome sequencing technology, it is now possible to study the genetic diversity of tuberculosis with much greater resolution. Although tuberculosis bacteria do not engage in horizontal gene transfer, the genome is far more variable than previously thought. The study of genome-wide variation in tuberculosis has improved our u...
#1Paolo Miotto (UniSR: Vita-Salute San Raffaele University)H-Index: 23
#2Ying Zhang (Johns Hopkins University)H-Index: 71
Last. Wing-Cheong Yam (HKU: University of Hong Kong)H-Index: 34
view all 4 authors...
: Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is the deadliest infectious disease and the associated global threat has worsened with the emergence of drug resistance, in particular multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Although the World Health Organization (WHO) End-TB Strategy advocates for universal access to antimicrobial susceptibility testing, this is not widely available and/or it is still underused. The majority of drug resistance in...
4 CitationsSource
#1Sebastien Gagneux (Swiss TPH: Swiss Tropical and Public Health Institute)H-Index: 58
Last. Lukas Fenner (University of Bern)H-Index: 20
view all 17 authors...
Background: Human tuberculosis (TB) is caused by seven phylogenetic lineages of the Mycobacterium tuberculosis complex (MTBC), Lineage 1–7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for rapid and phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, different strains of the MTBC influenc...