Towards the reconstruction of a global TB history using a new pipeline "TB-Annotator".

Mycobacterium tuberculosis complex (MTBC) has a population structure consisting of 9 human and animal lineages. The genomic diversity within these lineages is a pathogenesis factor that affects virulence, transmissibility, host response, and antibiotic resistance. Hence it is important to develop improved information systems for tracking and understanding the spreading and evolution of genomes. We present results obtained thanks to a new informatics platform for computational biology of MTBC, that uses a convenience sample from public/private SRAs, designated as TB-Annotator. Version 1 was a first interactive graphic-based web tool based on 15,901 representative genomes. Version 2, still interactive, is a more sophisticated database, developed using the Snakemake Workflow Management System (WMS) that allows an unsupervised global and scalable analysis of the content of the USA National Center for Biotechnology Information Short Read Archives database. This platform analyzes nucleotide variants, the presence/absence of genes, known regions of difference and detect new deletions, the insertion sites of mobile genetic elements, and allows phylogenetic trees to be built, imported in a graphical interface and interactively analyzed between the data and the tree. The objective of TB-Annotator is triple: detect recent epidemiological links, reconstruct distant phylogeographical histories as well as perform more complex phenotypic/genotypic Genome-Wide Association Studies (GWAS). In this paper, we compare the various taxonomic SNPs-based labels and hierarchies previously described in recent reference papers for L1, and present a comparative analysis that allows identification of alias and thus provides the basis of a future unifying naming scheme for L1 sublineages. We present a global phylogenetic tree built with RAxML-NG, and one on L2; at the time of writing, we characterized about 200 sublineages, with many new ones; a detail tree for Modern L2 and a hierarchical scheme allowing to facilitate L2 lineage assignment are also presented.

Mycobacterium tuberculosis complex drug-resistance, phylogenetics, and evolution in Nigeria: Comparison with Ghana and Cameroon.

In this article, we provide an in-depth analysis on the drug-resistance phenotypic characteristics of a cohort of 325 tuberculosis and characterize by Whole Genome Sequencing 24 isolates from Nigeria belonging to L4, L5 and L6. Our results suggest an alarming rate of drug-resistance of the L4.6.2.2 Mycobacterium tuberculosis complex (MTBC) lineage and a high diversity of L5. We compiled these new Sequence Read Archives (SRAs) to previously published ones from available Bioprojects run in Nigeria. We performed RAxML phylogenetic reconstructions of larger samples that include public NCBI SRAs from some neighboring countries (Cameroon, Ghana). To confront phylogenetic reconstruction to metadata, we used a new proprietary database named TB-Annotator. We show that L5 genomes in Northern Nigeria belong to new clades as the ones described until now and allow an update of the taxonomy of L5. In addition, we describe the L4.6.2.2 lineage in Nigeria, Cameroon and Ghana. We provide computations on the likely divergence time of L4.6.2.2 and suggest a new hypothesis concerning its origin. Finally we provide a short overview on M. bovis diversity in Nigeria. This study constitutes a baseline knowledge on the global genomic diversity, phylogeography and phylodynamics of MTBC in Nigeria, as well as on the natural history of this largely ignored but densely populated country of Africa. These results highlight the need of sequencing additional MTBC genomes in Nigeria and more generally in West-Africa, both for public health and for academic reasons. The likelihood of replacement of L5-L6 by L4.6.2.2 isolates, leave potentially little time to gather historical knowledge informative on the ancient history of tuberculosis in West-Africa.

Antibiotic resistance and the COVID-19 pandemic: A dual crisis with complex challenges in LMICs.

Background and Aims: Antimicrobial resistance (AMR), a global health crisis of mounting urgency, has been further complicated by the ongoing COVID-19 pandemic. The intricate relationship between these two phenomena is especially pronounced in low- and middle-income countries (LMICs) due to the distinct obstacles encountered by their healthcare systems and policy structures. This study aims to explore the complex challenges arising from the coexistence of these two crises in LMICs and proffer specific recommendations for holistic management. Methods: An exhaustive bibliographic survey was executed, employing search queries in specialized databases such as PubMed, SCOPUS, and Web of Science's SCI-EXPANDED index. The timeframe for the literature search extended from January 2020 to January 2023. The search strategy employed key terms including antibiotic resistance, AMR, COVID-19 pandemic, low- and middle-income countries, SARS-CoV-2, and LMICs. Results: The pandemic has aggravated various drivers of AMR in LMICs, including limited capabilities, weak frameworks, and socioeconomic factors. New challenges have emerged, such as disruptions in the antibiotic supply chain and an increased risk of healthcare-associated infections. The interaction between these drivers presents a complex problem that demands a coordinated response. Specific recommendations include strengthening health systems, funding research and innovation, and enhancing infection prevention control measures. Conclusion: The coexistence of AMR and the COVID-19 pandemic in LMICs demands an integrated approach involving multiple stakeholders. Emphasis must be placed on constructing aligned regulatory frameworks, nurturing regional collaborations, and focusing on accessible therapeutic options. The study underscores the necessity for actionable strategies to achieve sustainable access to clean water and sanitation and also highlights the importance of long-term planning, funding, and specialized expertise in emerging modalities like phage therapy.