published in Scientific Reports
Barbara Tizzano, Tobias K. Dallenga, Christian Utpatel, Jochen Behrends, Susanne Homolka, ThomasA. Kohl & Stefan Niemann
In this publication, Barbara Tizzano, Tobias Dallenga, Christian Utpatel, and colleagues showed that clinical isolates of not every lineage belonging to the M. tuberculosis complex are able to resuscitate from prolonged periods of oxygen starvation. Previous text book knowledge was that reactivation from dormanxy under hypoxic conditions was a common feature of all strains of the Mycobacterium tuberculosis complex. While all clinical isolates from different sub-lineages of lineage 4 (Euro-American) re-gained ability to proliferate, those belonging to lineage 1 (East African-Indian), lineage 2 (Beijing), and lineage 3 (Delhi/ Central Asian) did not reactivate upon exposure to oxygen in terms of growth, metabolism, and transcription. Transcriptome analysis showed a distinc gene expression program for H37Rb (L4) and Beijing (L2) upon oxygen starvation. These findings could provide deeper understanding in infection dynamics and epidemiology of different lineages of the Mycobacterium tuberculosis complex and may help to develop host-directed therapies and drugs that target the dormant state of mycobacteria.
Published in Nature Communications
Miguel Moreno-Molina, Natalia Shubladze , Iza Khurtsilava, Zaza Avaliani, Nino Bablishvili, Manuela Torres-Puente, Luis Villamayor, Andrei Gabrielian, Alex Rosenthal, Cristina Vilaplana, Sebastien Gagneux, Russell R. Kempker, Sergo Vashakidze & Iñaki Comas
Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0–5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient’s drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples.
published in International Journal of Systematic and Evolutionary Biology
Conor J. Meehan, Roman A. Barco, Yong-Hwee E. Loh, Sari Cogneau and Leen Rigouts
The definition of a genus has wide-ranging implications both in terms of binomial species names and also evolutionary relationships. In recent years, the definition of the genus Mycobacterium has been debated due to the proposed split of this genus into five new genera (Mycolicibacterium, Mycolicibacter, Mycolicibacillus, Mycobacteroides and an emended Mycobacterium). Since this group of species contains many important obligate and opportunistic pathogens, it is important that any renaming of species does not cause confusion in clinical treatment as outlined by the nomen periculosum rule (56a) of the Prokaryotic Code. In this study, we evaluated the proposed and original genus boundaries for the mycobacteria, to determine if the split into five genera was warranted. By combining multiple approaches for defining genus boundaries (16S rRNA gene similarity, amino acid identity index, average nucleotide identity, alignment fraction and percentage of conserved proteins) we show that the original genus Mycobacterium is strongly supported over the proposed five-way split. Thus, we propose that the original genus label be reapplied to all species within this group, with the proposed five genera potentially used as sub-genus complex names.