Global Genome Diversity and Recombination in Mycoplasma pneumoniae.
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ABSTRACT:
SUBMITTER: Hsieh YC
PROVIDER: S-EPMC8714221 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMycoplasma pneumoniae is a common pathogen that causes upper and lower respiratory tract infections in people of all ages, responsible for up to 40% of community-acquired pneumonias. It also causes a wide array of extrapulmonary infections and autoimmune phenomena. Phylogenetic studies of the organism have been generally restricted to specific genes or regions of the genome, because whole genome sequencing has been completed for only 4 strains. To better understand the physiology and pathogenicity of this important human pathogen, we performed comparative genomic analysis of 15 strains of M. pneumoniae that were isolated between the 1940s to 2009 from respiratory specimens and cerebrospinal fluid originating from the USA, China and England.ResultsIllumina MiSeq whole genome sequencing was performed on the 15 strains and all genome sequences were completed. Results from the comparative genomic analysis indicate that although about 1500 SNP and indel variants exist between type1 and type 2 strains, there is an overall high degree of sequence similarity among the strains (>99% identical to each other). Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed. The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex. Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes.ConclusionsThese data indicate that despite conclusions drawn from 16S rRNA sequences suggesting rapid evolution, the M. pneumoniae genome is extraordinarily stable over time and geographic distance across the globe with a striking lack of evidence of horizontal gene transfer.
| S-EPMC4537597 | biostudies-literature
Project description:Toxoplasma gondii is a highly successful protozoan parasite that infects all warm-blooded animals and causes severe disease in immunocompromised and immune-naïve humans. It has an unusual global population structure: In North America and Europe, isolated strains fall predominantly into four largely clonal lineages, but in South America there is great genetic diversity and the North American clonal lineages are rarely found. Genetic variation between Toxoplasma strains determines differences in virulence, modulation of host-signaling pathways, growth, dissemination, and disease severity in mice and likely in humans. Most studies on Toxoplasma genetic variation have focused on either a few loci in many strains or low-resolution genome analysis of three clonal lineages. We use whole-genome sequencing to identify a large number of SNPs between 10 Toxoplasma strains from Europe and North and South America. These were used to identify haplotype blocks (genomic regions) shared between strains and construct a Toxoplasma haplotype map. Additional SNP analysis of RNA-sequencing data of 26 Toxoplasma strains, representing global diversity, allowed us to construct a comprehensive genealogy for Toxoplasma gondii that incorporates sexual recombination. These data show that most current isolates are recent recombinants and cannot be easily grouped into a limited number of haplogroups. A complex picture emerges in which some genomic regions have not been recently exchanged between any strains, and others recently spread from one strain to many others.
| S-EPMC3421188 | biostudies-literature
Project description:Two main articles have used this data. The small bacterium Mycoplasma pneumoniae with its annotated 689 protein-coding genes and 44 RNAs constitutes an ideal system for global and conditional transcription analysis in bacteria. We have combined spotted arrays under more than 120 conditions with several strand-specific, high resolution tiling arrays to obtain an unprecedented level of detail of bacterial gene expression. We have found 68 new non-annotated transcripts, of which the vast majority are potential regulatory RNAs, 53 of them in antisense to known genes. Integration of all data confirmed a dynamic and complex view of bacterial transcription: Under reference conditions in a rich medium, 138 polycistronic and 212 monocistronic transcripts could be identified, with almost half of the polycistronic operons showing a ‘staircase’-like expression pattern, i.e. the expression level within each gene is constant, but succeeding genes have lower expression. Furthermore, under different conditions, operons can divide into smaller transcriptional units, possibly by utilization of internal promoters resulting in many alternative transcripts. More complex bacteria show similar responses to external stresses, although M. pneumoniae lacks the respective transcription regulators, indicating the existence of yet uncharacterized common response mechanisms. This is supported by the concerted expression of genes, some of which with common upstream DNA motifs, form distinct operons under different conditions indicating additional factors regulating their expression. Frequent antisense transcripts, alternative transcripts and multiple regulators per gene thus cannot longer be seen as indicators of eukaryote-specific regulatory complexity. Keywords: stress response, time series
2009-12-11 | GSE14014 | GEO
Project description:Two main articles have used this data. The small bacterium Mycoplasma pneumoniae with its annotated 689 protein-coding genes and 44 RNAs constitutes an ideal system for global and conditional transcription analysis in bacteria. We have combined spotted arrays under more than 120 conditions with several strand-specific, high resolution tiling arrays to obtain an unprecedented level of detail of bacterial gene expression. We have found 68 new non-annotated transcripts, of which the vast majority are potential regulatory RNAs, 53 of them in antisense to known genes. Integration of all data confirmed a dynamic and complex view of bacterial transcription: Under reference conditions in a rich medium, 138 polycistronic and 212 monocistronic transcripts could be identified, with almost half of the polycistronic operons showing a ‘staircase’-like expression pattern, i.e. the expression level within each gene is constant, but succeeding genes have lower expression. Furthermore, under different conditions, operons can divide into smaller transcriptional units, possibly by utilization of internal promoters resulting in many alternative transcripts. More complex bacteria show similar responses to external stresses, although M. pneumoniae lacks the respective transcription regulators, indicating the existence of yet uncharacterized common response mechanisms. This is supported by the concerted expression of genes, some of which with common upstream DNA motifs, form distinct operons under different conditions indicating additional factors regulating their expression. Frequent antisense transcripts, alternative transcripts and multiple regulators per gene thus cannot longer be seen as indicators of eukaryote-specific regulatory complexity. Keywords: Stress, genetic modification, time series, drug treatment
2009-12-11 | GSE14015 | GEO
Project description:Mycoplasmas are cell wall-less bacteria that evolved by drastic reduction of the genome size. Complete genome analysis of Mycoplasma pneumoniae revealed the presence of numerous copies of four distinct large M. pneumoniae repetitive elements (RepMPs). One copy each of RepMP2/3, RepMP4, and RepMP5 are localized within the P1 operon (MPN140 to MPN142 loci), and their involvement in sequence variation in adhesin P1 and adherence-related protein B/C has been documented. Here we analyzed a clinical strain of M. pneumoniae designated S1 isolated from a 1993 outbreak of respiratory infections in San Antonio, TX. Based on the type of RepMPs within the P1 operon, we classified clinical isolate S1 as type 2 with unique minor sequence variations. Hybridization with oligonucleotide arrays revealed sequence divergence in two previously unsuspected hypothetical genes (MPN137 and MPN138 loci). Closer inspection of this region revealed that the MPN137 and MPN138 loci harbored previously unrecognized unique RepMP1 sequences found only in M. pneumoniae. PCR and sequence analyses revealed a recombination event involving three RepMP1-containing genes that resulted in fusion of MPN137 and MPN138 reading frames and loss of all but a short fragment of another RepMP1-containing locus, MPN130. The multiple copies of unique RepMP1 elements spread throughout the chromosome could allow vast numbers of sequence variations in clinical strains. Comparisons of amino acid sequences showed the presence of leucine zipper motifs in MPN130 and MPN138 proteins in reference strain M129 and the absence of these motifs in the fused protein of S1. The presence of tandem leucine and other repeats points to possible regulatory functions of proteins encoded by RepMP1-containing genes.
| S-EPMC2292888 | biostudies-literature
Project description:The entire genome of the bacterium Mycoplasma pneumoniae M129 has been sequenced. It has a size of 816,394 base pairs with an average G+C content of 40.0 mol%. We predict 677 open reading frames (ORFs) and 39 genes coding for various RNA species. Of the predicted ORFs, 75.9% showed significant similarity to genes/proteins of other organisms while only 9.9% did not reveal any significant similarity to gene sequences in databases. This permitted us tentatively to assign a functional classification to a large number of ORFs and to deduce the biochemical and physiological properties of this bacterium. The reduction of the genome size of M. pneumoniae during its reductive evolution from ancestral bacteria can be explained by the loss of complete anabolic (e.g. no amino acid synthesis) and metabolic pathways. Therefore, M. pneumoniae depends in nature on an obligate parasitic lifestyle which requires the provision of exogenous essential metabolites. All the major classes of cellular processes and metabolic pathways are briefly described. For a number of activities/functions present in M. pneumoniae according to experimental evidence, the corresponding genes could not be identified by similarity search. For instance we failed to identify genes/proteins involved in motility, chemotaxis and management of oxidative stress.
| S-EPMC146264 | biostudies-other
Project description:The contribution of intracellular and fastidious bacteria in Cystic fibrosis (CF) pulmonary exacerbations, and progressive lung function decline remains unknown. This project aimed to explore their impact on bacterial microbiota diversity over time in CF children. Sixty-one children enrolled in the MUCOVIB multicentre prospective cohort provided 746 samples, mostly nasopharyngeal swabs, throat swabs and sputa which were analysed using culture, specific real-time qPCRs and 16S rRNA amplicon metagenomics. Chlamydia pneumoniae (n = 3) and Mycoplasma pneumoniae (n = 1) were prospectively documented in 6.6% of CF children. Microbiota alpha-diversity in children with a documented C. pneumoniae was highly variable, similarly to children infected with Staphylococcus aureus or Pseudomonas aeruginosa. The transition from routine follow-up visits to pulmonary exacerbation (n = 17) yielded variable changes in diversity indexes with some extreme loss of diversity. The high rate of C. pneumoniae detection supports the need for regular screenings in CF patients. A minor impact of C. pneumoniae on the microbial community structure was documented. Although detected in a single patient, M. pneumoniae should also be considered as a possible aetiology of lung infection in CF subjects.
| S-EPMC7787906 | biostudies-literature
Project description:Although Mycoplasma genitalium is a common sexually transmitted pathogen causing clinically distinct diseases both in male and females, few genomes have been sequenced up to now, due mainly to its fastidious nature and slow growth. Hence, we lack a robust phylogenetic framework to provide insights into the population structure of the species. Currently our understanding of the nature and diversity of M. genitalium relies on molecular tests targeting specific genes or regions of the genome and knowledge is limited by a general under-testing internationally. This is set against a background of drug resistance whereby M. genitalium has developed resistance to mainly all therapeutic antimicrobials.We sequenced 28 genomes of Mycoplasma genitalium from temporally (1980-2010) and geographically (Europe, Japan, Australia) diverse sources. All the strain showed essentially the same genomic content without any accessory regions found. However, we identified extensive recombination across their genomes with a total of 25 regions showing heightened levels of SNP density. These regions include the MgPar loci, associated with host interactions, as well as other genes that could also be involved in this role. Using these data, we generated a robust phylogeny which shows that there are two main clades with differing degrees of genomic variability. SNPs found in region V of 23S rRNA and parC were consistent with azithromycin/erythromycin and fluoroquinolone resistances, respectively, and with their phenotypic MIC data.The sequence data here generated is essential for designing rational approaches to type and track Mycoplasma genitalium as antibiotic resistance increases. It represents a first approach to its population genetics to better appreciate the role of this organism as a sexually transmitted pathogen.
| S-EPMC5745988 | biostudies-literature
Project description:DNA-binding proteins are central regulators of chromosome organization; however, in genome-reduced bacteria their diversity is largely diminished. Whether the chromosomes of such bacteria adopt defined three-dimensional structures remains unexplored. Here we combine Hi-C and super-resolution microscopy to determine the structure of the Mycoplasma pneumoniae chromosome at a 10 kb resolution. We find a defined structure, with a global symmetry between two arms that connect opposite poles, one bearing the chromosomal Ori and the other the midpoint. Analysis of local structures at a 3 kb resolution indicates that the chromosome is organized into domains ranging from 15 to 33 kb. We provide evidence that genes within the same domain tend to be co-regulated, suggesting that chromosome organization influences transcriptional regulation, and that supercoiling regulates local organization. This study extends the current understanding of bacterial genome organization and demonstrates that a defined chromosomal structure is a universal feature of living systems.
| S-EPMC5344976 | biostudies-literature
Project description: Not available
2015-06-19 | MSV000079167 | MassIVE