A New Phylogenetic Framework for the Animal-adapted<i>Mycobacterium tuberculosis</i>Complex

Brites, Daniela; Loiseau, Chloé; Menardo, Fabrizio; Borrell, Sònia; Boniotti, Maria Beatrice; Warren, Robin M.; Dippenaar, Anzaan; Parsons, Sven D.C.; Beisel, Christian; Behr, Marcel A.; Fyfe, Janet; Coscollá, Mireia; Gagneux, Sébastien

doi:10.1101/384263

Cited by 13 publications

(20 citation statements)

References 89 publications

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“…Similarly, also the closely related human-adapted M. africanum Lineage six seems to have mostly intact RD5 regions (Fig. 5;Brosch et al, 2002;Brites et al, 2018;Ates et al, 2018a). Together, these evolutionary observations suggest an advantage for the loss of the ppe38 locus only under specific conditions.…”

Section: Implications Of Pe and Ppe Gene Variation For The Evolution mentioning

confidence: 68%

“…caprae, M. orygis, M. suricattae and M. mungi, the Dassie Bacillus and a subset of M. microti strains isolated from voles Garnier et al, 2003;Mostowy et al, 2004;Dippenaar et al, 2015;Brites et al, 2018). In fact, the only known animal adapted MTBC members that have retained the RD5 locus are the Chimpanzee bacillus, M. pinnipedii and a subset of M. microti isolates isolated from humans Coscolla et al, 2013;Brites et al, 2018). Similarly, also the closely related human-adapted M. africanum Lineage six seems to have mostly intact RD5 regions (Fig.…”

Section: Implications Of Pe and Ppe Gene Variation For The Evolution mentioning

confidence: 99%

“…The RD1/ESX-1dependent rupture of phagosomal membranes that leads to cellular necrosis and extracellular bacilli may be particularly important for aerosol transmission and may be less important when direct contact between infected and noninfected tissues occurs regularly (van der Wel et al, 2007;Simeone et al, 2012;Houben et al, 2012a;Gröschel et al, 2016;Dallenga et al, 2017). Since the ESX-1 substrates are highly immunogenic, the potential reduction of virulence could be offset by a reduction in antigenic recognition of the pathogen, especially in this context of (Brites et al, 2018). Independent RD5 deletions, with unique remaining flanking sequences, are depicted in the phylogenetic tree.…”

Section: Implications Of Pe and Ppe Gene Variation For The Evolution mentioning

confidence: 99%

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New insights into the mycobacterial PE and PPE proteins provide a framework for future research

Ates

2019

Molecular Microbiology

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The PE and PPE proteins of Mycobacterium tuberculosis have been studied with great interest since their discovery. Named after the conserved proline (P) and glutamic acid (E) residues in their N-terminal domains, these proteins are postulated to perform wide-ranging roles in virulence and immune modulation. However, technical challenges in studying these proteins and their encoding genes have hampered the elucidation of molecular mechanisms and leave many open questions regarding the biological functions mediated by these proteins. Here, I review the shared and unique characteristics of PE and PPE proteins from a molecular perspective linking this information to their functions in mycobacterial virulence. I discuss how the different subgroups (PE_PGRS, PPE-PPW, PPE-SVP and PPE-MPTR) are defined and why this classification of paramount importance to understand the PE and PPE proteins as individuals and or groups. The goal of this MicroReview is to summarize and structure the existing information on this gene family into a simplified framework of thinking about PE and PPE proteins and genes. Thereby, I hope to provide helpful starting points in studying these genes and proteins for researchers with different backgrounds. This has particular implications for the design and monitoring of novel vaccine candidates and in understanding the evolution of the M. tuberculosis complex.

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Section: Implications Of Pe and Ppe Gene Variation For The Evolution mentioning

confidence: 68%

Section: Implications Of Pe and Ppe Gene Variation For The Evolution mentioning

confidence: 99%

Section: Implications Of Pe and Ppe Gene Variation For The Evolution mentioning

confidence: 99%

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New insights into the mycobacterial PE and PPE proteins provide a framework for future research

Ates

2019

Molecular Microbiology

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“…Intense research has been dedicated to decipher the evolutionary history of the MTBC and to understand the causes underlying the worldwide spread of TB [3][4][5] . Current genome data show that the MTBC is comprised of two main branches, one including the five human-adapted lineages representing M. tuberculosis sensu stricto (L1-4, and L7), and the second branch comprising two other human-adapted lineages traditionally referred to as M. africanum (L5-6) and at least nine animal-adapted lineages 6 . Africa is the only continent where all MTBC lineages are present, suggesting that the MTBC emerged from a common ancestor therein and then clonally expanded to the rest of the world following human migrations 3,7,8 .…”

Section: Introductionmentioning

confidence: 99%

A sister lineage of theMycobacterium tuberculosis complexdiscovered in the African Great Lakes region

Ngabonziza

Loiseau

Marceau

et al. 2020

Preprint

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The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to have clonally expanded from a common progenitor in Africa. However, the molecular events that accompanied this emergence remain largely unknown. Here, we describe two MTBC strains isolated from patients with multidrug-resistant tuberculosis, representing an as-yet-unknown lineage, named Lineage 8 (L8), seemingly restricted to the African Great Lakes region. Using genome-based phylogenetic reconstruction, we show that L8 is a sister clade to the known MTBC lineages. Comparison with other complete mycobacterial genomes indicate that the divergence of L8 preceded the loss of the cobF genome region - involved in the cobalamin/vitamin B12 synthesis - and gene interruptions in a subsequent common ancestor shared by all other known MTBC lineages. This discovery further supports an East African origin for the MTBC and provides additional molecular clues on the ancestral genome reduction associated with adaptation to a pathogenic lifestyle.

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“…Mtb is an obligate human pathogen and comprises seven phylogenetic lineages, each with a distinct geographic distribution. Together with several animal-adapted lineages (Brites et al, 2018), these make up the "Mtb complex" (Gagneux, 2018). Even though the Mtb complex harbors little genetic diversity compared to other bacteria (Achtman, 2008), Mtb clinical strains differ significantly in virulence and transmissibility Gagneux, 2010, 2014).…”

Section: Introductionmentioning

confidence: 99%

Network analysis identifies regulators of lineage-specific phenotypes inMycobacterium tuberculosis

Banaei‐Esfahani

Trauner

Borrell

et al. 2020

Preprint

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Highlights Proteomic and transcriptomic characterization of fully sequenced diverse L1 and L2 clinical isolates of Mtb. Post-transcriptional control mechanisms for regulatory and virulence genes are mitigated in Mtb L2. By applying a genome-scale transcriptional framework, DosR, Rv1985c, Lsr2 and Rv0691c are identified as master transcription factors responsible for differential target gene expression in L2 strains compared to L1. L1 and L2 DosR proteins respond differently to nitric oxide stress, thus determining a relevant phenotype. SummaryThe Mycobacterium tuberculosis (Mtb) complex comprises seven phylogenetically distinct human-adapted lineages exhibiting different geographical distribution and degrees of pathogenicity. Among these, Lineage 1 (L1) has been associated with low virulence whereas Lineage 2 (L2) has been linked to hyper-virulence, enhanced transmission and drug resistance.Here, we conducted multi-layer comparative analyses using whole genome sequencing data combined with quantitative transcriptomic and proteomic profiling of a set of L1 and L2 clinical strains, each grown under two different conditions in vitro. Our data revealed different degrees of correlation between transcript and protein abundances across clinical strains and functional gene categories, indicating variable levels of post-transcriptional regulation in the tested lineages. Contrasting genomic and gene expression data showed that the magnitude of the transcriptional and translational changes was proportional to the phylogenetic distance between strains, with one out of three single nucleotide polymorphisms leading to a transcriptional and/or translational change on average. We devised a new genome-scale transcriptional regulatory model and identified several master transcription factors, strongly linked to the sigma factor network, whose targets were differentially regulated between the two lineages. These differences resulted in a higher basal expression of DosR proteins and a stronger response to nitric oxide (NO) exposure in L2 compared to L1. These patterns are most likely responsible for the shorter NO-induced growth arrest in L2 observed. Given the limited genetic variation between strains, it appears that phenotypic differences in Mtb are substantially driven by differences in the regulation of biochemical networks through master transcriptional regulators.

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A New Phylogenetic Framework for the Animal-adaptedMycobacterium tuberculosisComplex

Abstract: 35Tuberculosis (TB) affects humans and other animals and is caused by bacteria from the

Cited by 13 publications

References 89 publications

New insights into the mycobacterial PE and PPE proteins provide a framework for future research

New insights into the mycobacterial PE and PPE proteins provide a framework for future research

A sister lineage of theMycobacterium tuberculosis complexdiscovered in the African Great Lakes region

Network analysis identifies regulators of lineage-specific phenotypes inMycobacterium tuberculosis

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