Large genomic deletions delineate Mycobacterium tuberculosis L4 sublineages in South American countries

Abstract

Mycobacterium tuberculosis (Mtb) is still one of the primary pathogens of humans causing tuberculosis (TB) disease. Mtb embraces nine well-defined phylogenetic lineages with biological and geographical disparities. The lineage L4 is the most globally widespread of all lineages and was introduced to America with European colonization. Taking advantage of many genome projects available in public repositories, we undertake an evolutionary and comparative genomic analysis of 522 L4 Latin American Mtb genomes. Initially, we performed careful quality control of public read datasets and applied several thresholds to filter out low-quality data. Using a genome de novo assembly strategy and phylogenomic methods, we spotted novel south American clades that have not been revealed yet. Additionally, we describe genomic deletion profiles of these strains from an evolutionary perspective and report Mycobacterium tuberculosis L4 sublineages signature-like gene deletions, some of the novel. One is a specific deletion of 6.5 kbp that is only present in sublineage 4.1.2.1. This deletion affects a complex group of 10 genes with putative products annotated, among others, as a lipoprotein, transmembrane protein, and toxin/antitoxin system proteins. The second novel deletion spans for 4.9 kbp and specific of a particular clade of the 4.8 sublineage and affects 7 genes. The last novel deletion affects 4 genes, extends for 4.8 kbp., and is specific to some strains within the 4.1.2.1 sublineage that are present in Colombia, Peru and Brasil.

TheMycobacterium tuberculosiscomplex pangenome is small and driven by sub-lineage-specific regions of difference

“…We showed that MTBC has a compact accessory genome that is acquired verTcally. This finding is consistent with recent research, which found a small accessory genome with a clonal geneTc structure in MTBC (Baena et al, 2023, Ceres et al, 2022, Silva-Pereira et al, 2024. Using a BLASTn analysis approach, we idenTfied core genes that were designated as accessory and further reduced the accessory genome from 613 to 506.…”

“…It comprises both the core genome, which consists of genes shared by all members of the species, and the accessory genome, which includes genes present in some but not all members (Brockhurst et al, 2019). Previous research has focused on pangenomic invesTgaTons of parTcular MTBC lineages (Baena et al, 2023, Ceres et al, 2022. A recent study invesTgated the MTBC pangenome focusing on protein-coding sequences (Silva-Pereira et al, 2024).…”

Phylogenomic discernments into Anaerolineaceae thermal adaptations and the proposal of a candidate genus Mesolinea

“…The number of genes per genome is also reduced in Clade II, aligning with the observed differences in genome sizes. However, the average protein length remains nearly the same in both clades, suggesting that genome reduction in Clade II may be associated with gene losses, possibly through genome deletions observed in other bacteria (Hershberg et al, 2007;Koskiniemi et al, 2012;Bobay and Ochman, 2017;Baena et al, 2023). Given that many genomes in Clade II are metagenomeassembled genomes (MAGs), future confirmatory analyses are crucial to mitigate potential effects of incomplete genomes on statistical analyses.…”

Tuberculosis Severity Predictive Model Using Mtb Variants and Serum Biomarkers in a Colombian Cohort of APTB Patients

“…The Mtb genomes were sequenced by Novogene (Sacramento, CA, USA) using the Illumina Novaseq 6000 platform, analyzed, and deposited in the NCBI SRA database under the bioproject PRJNA867148 [43].…”