Dataset Information

Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.

ABSTRACT: BACKGROUND: Mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably Mycobacterium tuberculosis. Considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, the aim of this study was to conduct a comparative genomics analysis of the repertoire of enzymes involved in peptidoglycan (PG) remodelling to determine the potential of exploiting this area of bacterial metabolism for the discovery of new drug targets. RESULTS: We conducted an in silico analysis of 19 mycobacterial species/clinical strains for the presence of genes encoding resuscitation promoting factors (Rpfs), penicillin binding proteins, endopeptidases, L,D-transpeptidases and N-acetylmuramoyl-L-alanine amidases. Our analysis reveals extensive genetic multiplicity, allowing for classification of mycobacterial species into three main categories, primarily based on their rpf gene complement. These include the M. tuberculosis Complex (MTBC), other pathogenic mycobacteria and environmental species. The complement of these genes within the MTBC and other mycobacterial pathogens is highly conserved. In contrast, environmental strains display significant genetic expansion in most of these gene families. Mycobacterium leprae retains more than one functional gene from each enzyme family, underscoring the importance of genetic multiplicity for PG remodelling. Notably, the highest degree of conservation is observed for N-acetylmuramoyl-L-alanine amidases suggesting that these enzymes are essential for growth and survival. CONCLUSION: PG remodelling enzymes in a range of mycobacterial species are associated with extensive genetic multiplicity, suggesting functional diversification within these families of enzymes to allow organisms to adapt.

SUBMITTER: Machowski EE

PROVIDER: S-EPMC3987819 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.

Machowski Edith Erika EE Senzani Sibusiso S Ealand Christopher C Kana Bavesh Davandra BD

BMC microbiology 20140324

<h4>Background</h4>Mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably Mycobacterium tuberculosis. Considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, the aim of this study was to conduct a comparative genomics analysis of the repertoire of enzymes involved in peptidoglycan (PG) remodelling to determine the potential of exploiting this area of bacterial metaboli ...[more]

PMID: 24661741

Similar Datasets

Project description:BackgroundMicrococcus luteus is a group of actinobacteria that is widely used in biotechnology and is being thought as an emerging nosocomial pathogen. With one of the smallest genomes of free-living actinobacteria, it is found in a wide range of environments, but intraspecies genetic diversity and adaptation strategies to various environments remain unclear. Here, comparative genomics, phylogenomics, and genome-wide association studies were used to investigate the genomic diversity, evolutionary history, and the potential ecological differentiation of the species.ResultsHigh-quality genomes of 66?M. luteus strains were downloaded from the NCBI GenBank database and core and pan-genome analysis revealed a considerable intraspecies heterogeneity. Phylogenomic analysis, gene content comparison, and average nucleotide identity calculation consistently indicated that the species has diverged into three well-differentiated clades. Population structure analysis further suggested the existence of an unknown ancestor or the fourth, yet unsampled, clade. Reconstruction of gene gain/loss events along the evolutionary history revealed both early events that contributed to the inter-clade divergence and recent events leading to the intra-clade diversity. We also found convincing evidence that recombination has played a key role in the evolutionary process of the species, with upto two-thirds of the core genes having been affected by recombination. Furthermore, distribution of mammal-associated strains (including pathogens) on the phylogenetic tree suggested that the last common ancestor had a free-living lifestyle, and a few recently diverged lineages have developed a mammal-associated lifestyle separately. Consistently, genome-wide association analysis revealed that mammal-associated strains from different lineages shared genes functionally relevant to the host-associated lifestyle, indicating a recent ecological adaption to the new host-associated habitats.ConclusionsThese results revealed high intraspecies genomic diversity of M. luteus and highlighted that gene gain/loss events and extensive recombination events played key roles in the genome evolution. Our study also indicated that, as a free-living species, some lineages have recently developed or are developing a mammal-associated lifestyle. This study provides insights into the mechanisms that drive the genome evolution and adaption to various environments of a bacterial species.

Project description:Ruminococcus gnavus is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of R. gnavus. We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of R. gnavus was 42.73±0.33 mol%, and the mean genome size was 3.46±0.34 Mbp. Genome-wide evolutionary analysis revealed R. gnavus genomes were divided into three major phylogenetic clusters. Pan-core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74 % (1051/28 072), 1.75 % (491/28 072), 9.88 % (2774/28 072) and 84.63 % (23 756/28 072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among R. gnavus strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are tetO (tetracycline-resistance gene, present in 75 strains) and cps4J (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of R. gnavus. This study provides new insights for understanding the genomic features and health relevance of R. gnavus, and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.

Project description:BACKGROUND:Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous. RESULTS:In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to >?13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively. CONCLUSIONS:The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding.

Dataset Information

Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.

Publications

Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets