Genetic Basis of Virulence Attenuation Revealed by Comparative Genomic Analysis of Mycobacterium tuberculosis Strain H37Ra versus H37Rv

Bacteria belonging to the genus Aminobacter are metabolically versatile organisms thriving in both natural and anthropized terrestrial environments. To date, the taxonomy of this genus is poorly defined due to the unavailability of the genomic sequence of A. anthyllidis LMG 26462T and the presence of unclassified Aminobacter strains. Here, we determined the genome sequence of A. anthyllidis LMG 26462T and performed phylogenomic, average nucleotide identity and digital DNA-DNA hybridization analyses of 17 members of genus Aminobacter. Our results indicate that 16S rRNA-based phylogeny does not provide sufficient species-level discrimination, since most of the unclassified Aminobacter strains belong to valid Aminobacter species or are putative new species. Since some members of the genus Aminobacter can utilize certain C1 compounds, such as methylamines and methyl halides, a comparative genomic analysis was performed to characterize the genetic basis of some degradative/assimilative pathways in the whole genus. Our findings suggest that all Aminobacter species are heterotrophic methylotrophs able to generate the methylene tetrahydrofolate intermediate through multiple oxidative pathways of C1 compounds and convey it in the serine cycle. Moreover, all Aminobacter species carry genes implicated in the degradation of phosphonates via the C-P lyase pathway, whereas only A. anthyllidis LMG 26462T contains a symbiosis island implicated in nodulation and nitrogen fixation.

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Comparative Genomic Analysis of Two Clonally Related Multidrug Resistant Mycobacterium tuberculosis by Single Molecule Real Time Sequencing

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2017.00478 ◽

2017 ◽

Vol 7 ◽

Cited By ~ 4

Author(s):

Kenneth Siu-Sing Leung ◽

Gilman Kit-Hang Siu ◽

Kingsley King-Gee Tam ◽

Sabrina Wai-Chi To ◽

Rahim Rajwani ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Real Time ◽

Single Molecule ◽

Genomic Analysis ◽

Multidrug Resistant ◽

Comparative Genomic Analysis ◽

Comparative Genomic

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Comparative Genomic Analysis of Mycobacterium tuberculosis Drug Resistant Strains from Russia

PLoS ONE ◽

10.1371/journal.pone.0056577 ◽

2013 ◽

Vol 8 (2) ◽

pp. e56577 ◽

Cited By ~ 32

Author(s):

Elena N. Ilina ◽

Egor A. Shitikov ◽

Larisa N. Ikryannikova ◽

Dmitry G. Alekseev ◽

Dmitri E. Kamashev ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Genomic Analysis ◽

Comparative Genomic Analysis ◽

Comparative Genomic ◽

Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains

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Comparative genomic analysis ofBrucella abortusvaccine strain 104M reveals a set of candidate genes associated with its virulence attenuation

Virulence ◽

10.1080/21505594.2015.1038015 ◽

2015 ◽

Vol 6 (8) ◽

pp. 745-754 ◽

Cited By ~ 10

Author(s):

Dong Yu ◽

Yiming Hui ◽

Xiaodong Zai ◽

Junjie Xu ◽

Long Liang ◽

...

Keyword(s):

Candidate Genes ◽

Genomic Analysis ◽

Comparative Genomic Analysis ◽

Comparative Genomic ◽

Virulence Attenuation

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Comparative genomic analysis of Mycobacterium tuberculosis reveals evolution and genomic instability within Uganda I sub-lineage

10.1101/2020.10.24.353425 ◽

2020 ◽

Author(s):

Stephen Kanyerezi ◽

Patricia Nabisubi

Keyword(s):

Mycobacterium Tuberculosis ◽

Core Genome ◽

Variant Calling ◽

Genomic Analysis ◽

Comparative Genomic Analysis ◽

Genome Wide Association ◽

Comparative Genomic ◽

Pan Genome ◽

Genome Wide

AbstractIntroductionTuberculosis (TB) is the leading cause of morbidity and mortality globally, responsible for an estimated annual 10.0 million new cases and 1.3 million deaths among infectious diseases with Africa contributing a quarter of these cases in 2019. Classification of Mycobacterium tuberculosis (MTB) strains is important in understanding their geographical predominance and pathogenicity. Different studies have gone ahead to classify MTB using different methods. Some of these include; RFLP, spoligotyping, MIRU-VNTR and SNP set based phylogeny. The SNP set based classification has been found to be in concordance with the region of difference (RD) analysis of MTB complex classification system. In Uganda, the most common cause of pulmonary tuberculosis (PTB) is Uganda genotype of MTB and accounts for up to 70 % of isolates.MethodsSequenced MTB genome samples were retrieved from NCBI and others from local sequencing projects. The genomes were subjected to snippy (a rapid haploid variant calling and core genome alignment) to call variants and annotate them. Outputs from snippy were used to classify the isolates into Uganda genotypes and Non Ugandan genotypes based on 62 SNP set. The Ugandan genotype isolates were later subjected to 413 SNP set and then to a pan genome wide association analysis.Results6 Uganda genotype isolates were found not to classify as either Uganda I or II genotypes based on the 62 SNP set. Using the 413 SNP set, the 6 Uganda genotype isolates were found to have only one SNP out of the 7 SNPs that classify the Uganda I genotypes. They were also found to have both missense and frameshift mutations within the ctpH gene whereas the rest of Uganda I that had a mutation within this gene, was a missense.ConclusionAmong the Uganda genotypes genomes, Uganda I genomes are unstable. We used publicly available datasets to perform analysis like mapping, variant calling, mixed infection, pan-genome analysis to investigate and compare evolution of the Ugandan genotype.

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Comparative Genomic Analysis of Mycobacteriaceae Reveals Horizontal Gene Transfer-Mediated Evolution of the CRISPR-Cas System in the Mycobacterium tuberculosis Complex

mSystems ◽

10.1128/msystems.00934-20 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Anoop Singh ◽

Mohita Gaur ◽

Vishal Sharma ◽

Palak Khanna ◽

Ankur Bothra ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Common Ancestor ◽

Genomic Analysis ◽

Comparative Genomic Analysis ◽

Comparative Genomic ◽

Last Common Ancestor ◽

Content Type ◽

Type Iii

ABSTRACT Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes are conserved genetic elements in many prokaryotes, including Mycobacterium tuberculosis, the causative agent of tuberculosis. Although knowledge of CRISPR locus variability has been utilized in M. tuberculosis strain genotyping, its evolutionary path in Mycobacteriaceae is not well understood. In this study, we have performed a comparative analysis of 141 mycobacterial genomes and identified the exclusive presence of the CRISPR-Cas type III-A system in M. tuberculosis complex (MTBC). Our global phylogenetic analysis of CRISPR repeats and Cas10 proteins offers evidence of horizontal gene transfer (HGT) of the CRISPR-Cas module in the last common ancestor of MTBC and Mycobacterium canettii from a Streptococcus-like environmental bacterium. Additionally, our results show that the variation of CRISPR-Cas organization in M. tuberculosis lineages, especially in the Beijing sublineage of lineage 2, is due to the transposition of insertion sequence IS6110. The direct repeat (DR) region of the CRISPR-Cas locus acts as a hot spot for IS6110 insertion. We show in M. tuberculosis H37Rv that the repeat at the 5′ end of CRISPR1 of the forward strand is an atypical repeat made up partly of IS-terminal inverted repeat and partly CRISPR DR. By tracing an undetectable spacer sequence in the DR region, the two CRISPR loci could theoretically be joined to reconstruct the ancestral single CRISPR-Cas locus organization, as seen in M. canettii. This study retracing the evolutionary events of HGT and IS6110-driven genomic deletions helps us to better understand the strain-specific variations in M. tuberculosis lineages. IMPORTANCE Comparative genomic analysis of prokaryotes has led to a better understanding of the biology of several pathogenic microorganisms. One such clinically important pathogen is M. tuberculosis, the leading cause of bacterial infection worldwide. Recent evidence on the functionality of the CRISPR-Cas system in M. tuberculosis has brought back focus on these conserved genetic elements, present in many prokaryotes. Our study advances understanding of mycobacterial CRISPR-Cas origin and its diversity among the different species. We provide phylogenetic evidence of acquisition of CRISPR-Cas type III-A in the last common ancestor shared between MTBC and M. canettii, by HGT-mediated events. The most likely source of HGT was an environmental Firmicutes bacterium. Genomic mapping of the CRISPR loci showed the IS6110 transposition-driven variations in M. tuberculosis strains. Thus, this study offers insights into events related to the evolution of CRISPR-Cas in M. tuberculosis lineages.

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