Whole genome shotgun sequencing of one Colombian clinical isolate of Mycobacterium tuberculosis reveals DosR regulon gene deletions

Abstract

Several genomes of different Mycobacterium tuberculosis isolates have been completely sequenced around the world. The genomic information obtained have shown higher diversity than originally thought and specific adaptations to different human populations. Within this work, we sequenced the genome of one Colombian M. tuberculosis virulent isolate. Genomic comparison against the reference genome of H37Rv and other strains showed multiple deletion and insertions that ranged between a few bases to thousands. Excluding PPE and PG-PGRS genes, 430 proteins present changes in at least 1 amino acid. Also, novel positions of the IS6110 mobile element were identified. This isolate is also characterized by a large genomic deletion of 3.6 kb, leading to the loss and modification of the dosR regulon genes, Rv1996 and Rv1997. To our knowledge, this is the first report of the genome sequence of a Latin American M. tuberculosis clinical isolate.

Infection of Monocytes From Tuberculosis Patients With Two Virulent Clinical Isolates of Mycobacterium tuberculosis Induces Alterations in Myeloid Effector Functions

“…To investigate the biological pathways and critical processes in the pathogenesis of TB potentially mediated by circulating monocytes, we first analyzed the systemic effect of TB on the baseline genome-wide gene expression profiles of MoTB compared to MoCT. Second, MoCT and MoTB were infected for 6 h at a multiplicity of infection of 10:1 with two Colombian clinical isolates of Mtb, UT127 and UT205, that may differ in virulence (Isaza et al, 2012;Duque et al, 2014;Baena et al, 2019), and then their transcriptional profiles were investigated.…”

“…A posterior study (Duque et al, 2014) indicated that infection of human monocytes (MOI 10:1) with UT205 for 24 h induced a higher proportion of cells with membrane damage compared to UT127, suggesting differences in virulence between these two isolates. We also sequenced the genomes of both isolates (Isaza et al, 2012;Baena et al, 2019), which are 99.6% identical. Interestingly, they display significant transcriptomic differences when growth in axenic media (Baena et al, 2019) besides their extensive genomic similarity.…”

Two-Component Signalling Systems of M. tuberculosis: Regulators of Pathogenicity and More

“…Although this system has been extensively characterized at the molecular level, there are some observations, including one mentioned above, which are yet to be explained. For example, clinical isolates of M. tuberculosis from Colombia have recently shown to harbour a 3.6 kb deletion resulting in a loss of the DevR regulon genes [106]. The strain appears to have retained its virulence despite the lack of this apparently virulence determining gene segment.…”

Bacterial Bio-Resources for Remediation of Hexachlorocyclohexane

“…It is important to note that recently, Isaza et al [100] identify a haloalkane dehalogenasa (LinB) belonging to Mycobacterium tuberculosis CDC1551. This protein of 300 aminoacids, showed 100% homology to Mycobacterium tuberculosis KZN 605, Mycobacterium bobis BCG STR Pasteur 117 and 98% homology to Sphingobiun francensis and Sphingobiun sp.…”