102 research outputs found
Differentiation of regions with atypical oligonucleotide composition in bacterial genomes
BACKGROUND: Complete sequencing of bacterial genomes has become a common technique of present day microbiology. Thereafter, data mining in the complete sequence is an essential step. New in silico methods are needed that rapidly identify the major features of genome organization and facilitate the prediction of the functional class of ORFs. We tested the usefulness of local oligonucleotide usage (OU) patterns to recognize and differentiate types of atypical oligonucleotide composition in DNA sequences of bacterial genomes. RESULTS: A total of 163 bacterial genomes of eubacteria and archaea published in the NCBI database were analyzed. Local OU patterns exhibit substantial intrachromosomal variation in bacteria. Loci with alternative OU patterns were parts of horizontally acquired gene islands or ancient regions such as genes for ribosomal proteins and RNAs. OU statistical parameters, such as local pattern deviation (D), pattern skew (PS) and OU variance (OUV) enabled the detection and visualization of gene islands of different functional classes. CONCLUSION: A set of approaches has been designed for the statistical analysis of nucleotide sequences of bacterial genomes. These methods are useful for the visualization and differentiation of regions with atypical oligonucleotide composition prior to or accompanying gene annotation
Global features of sequences of bacterial chromosomes, plasmids and phages revealed by analysis of oligonucleotide usage patterns
BACKGROUND: Oligonucleotide frequencies were shown to be conserved signatures for bacterial genomes, however, the underlying constraints have yet not been resolved in detail. In this paper we analyzed oligonucleotide usage (OU) biases in a comprehensive collection of 155 completely sequenced bacterial chromosomes, 316 plasmids and 104 phages. RESULTS: Two global features were analyzed: pattern skew (PS) and variance of OU deviations normalized by mononucleotide content of the sequence (OUV). OUV reflects the strength of OU biases and taxonomic signals. PS denotes asymmetry of OU in direct and reverse DNA strands. A trend towards minimal PS was observed for almost all complete sequences of bacterial chromosomes and plasmids, however, PS was substantially higher in separate genomic loci and several types of plasmids and phages characterized by long stretches of non-coding DNA and/or asymmetric gene distribution on the two DNA strands. Five of the 155 bacterial chromosomes have anomalously high PS, of which the chromosomes of Xylella fastidiosa 9a5c and Prochlorococcus marinus MIT9313 exhibit extreme PS values suggesting an intermediate unstable state of these two genomes. CONCLUSIONS: Strand symmetry as indicated by minimal PS is a universally conserved feature of complete bacterial genomes that results from the matching mutual compensation of local OU biases on both replichors while OUV is more a taxon specific feature. Local events such as inversions or the incorporation of genome islands are balanced by global changes in genome organization to minimize PS that may represent one of the leading evolutionary forces driving bacterial genome diversification
The epistatic landscape of antibiotic resistance of different clades of Mycobacterium tuberculosis
Drug resistance (DR) remains a global challenge in tuberculosis (TB) control. In order to
develop molecular-based diagnostic methods to replace the traditional culture-based diagnostics,
there is a need for a thorough understanding of the processes that govern TB drug resistance. The
use of whole-genome sequencing coupled with statistical and computational methods has shown
great potential in unraveling the complexity of the evolution of DR-TB. In this study, we took an
innovative approach that sought to determine nonrandom associations between polymorphic sites in
Mycobacterium tuberculosis (Mtb) genomes. Attributable risk statistics were applied to identify the
epistatic determinants of DR in different clades of Mtb and the possible evolutionary pathways of DR
development. It was found that different lineages of Mtb exploited different evolutionary trajectories
towards multidrug resistance and compensatory evolution to reduce the DR-associated fitness cost.
Epistasis of DR acquisition is a new area of research that will aid in the better understanding of
evolutionary biological processes and allow predicting upcoming multidrug-resistant pathogens
before a new outbreak strikes humanity.The South African National Research Foundation (NRF)https://www.mdpi.com/journal/antibioticsam2022BiochemistryGeneticsMicrobiology and Plant Patholog
Analysis of genomic rearrangements, horizontal gene transfer and role of plasmids in the evolution of industrial important Thermus species
BACKGROUND: Bacteria of genus Thermus inhabit both man-made and natural thermal environments. Several
Thermus species have shown biotechnological potential such as reduction of heavy metals which is essential for
eradication of heavy metal pollution; removing of organic contaminants in water; opening clogged pipes,
controlling global warming among many others. Enzymes from thermophilic bacteria have exhibited higher activity
and stability than synthetic or enzymes from mesophilic organisms.
RESULTS: Using Meiothermus silvanus DSM 9946 as a reference genome, high level of coordinated rearrangements
has been observed in extremely thermophilic Thermus that may imply existence of yet unknown evolutionary
forces controlling adaptive re-organization of whole genomes of thermo-extremophiles. However, no remarkable
differences were observed across species on distribution of functionally related genes on the chromosome
suggesting constraints imposed by metabolic networks. The metabolic network exhibit evolutionary pressures
similar to levels of rearrangements as measured by the cross-clustering index. Using stratigraphic analysis of
donor-recipient, intensive gene exchanges were observed from Meiothermus species and some unknown sources to
Thermus species confirming a well established DNA uptake mechanism as previously proposed.
CONCLUSION: Global genome rearrangements were found to play an important role in the evolution of Thermus
bacteria at both genomic and metabolic network levels. Relatively higher level of rearrangements was observed in
extremely thermophilic Thermus strains in comparison to the thermo-tolerant Thermus scotoductus. Rearrangements
did not significantly disrupt operons and functionally related genes. Thermus species appeared to have a developed
capability for acquiring DNA through horizontal gene transfer as shown by the donor-recipient stratigraphic analysis.http://www.biomedcentral.com/bmcgenomics/am201
Distribution of horizontally transferred heavy metal resistance operons in recent outbreak bacteria
Mankind is confronted by the outbreaks
of highly virulent and
multi-drug resistant pathogens. The
outbreak strains often belong to wellknown
disease-associated species belonging
to genera such as Salmonella,
Klebsiella and Mycobacterium, but even
normally commensal and environmental
microorganisms may suddenly acquire
properties of virulent bacteria and cause
nosocomial infections. The acquired virulence
is often associated with lateral
exchange of pathogenicity genomic
islands containing drug and heavy metal
resistance determinants. Metal ions are
used by the immune system of macroorganisms
against bactericidal agents.
The ability to control heavy metal
homeostasis is a factor that allows the
survival of pathogenic microorganisms in
macrophages. In this paper, we investigate
the origin of heavy metal resistance
operons in the recent outbreak strains and
the possible routes which may lead to
acquisitions of these genes by potentially
new pathogens. We hypothesize that new
outbreak microorganisms appear intermittently
on an intersection of the nonspecialized,
genetically naïve strains of
potential pathogens and virulence factor
comprising vectors (plasmid and/or phages)
newly generated in the environmental
microflora. Global contamination of the
environment and climate change may also
have an effect toward the acceleration and
appearance of new pathogens.The National
Research Foundation of South Africa
grant NRF 71261.http://www.landesbioscience.com/journals/mge
The SeqWord Genome Browser: an online tool for the identification and visualization of atypical regions of bacterial genomes through oligonucleotide usage
<p>Abstract</p> <p>Background</p> <p>Data mining in large DNA sequences is a major challenge in microbial genomics and bioinformatics. Oligonucleotide usage (OU) patterns provide a wealth of information for large scale sequence analysis and visualization. The purpose of this research was to make OU statistical analysis available as a novel web-based tool for functional genomics and annotation. The tool is also available as a downloadable package.</p> <p>Results</p> <p>The SeqWord Genome Browser (SWGB) was developed to visualize the natural compositional variation of DNA sequences. The applet is also used for identification of divergent genomic regions both in annotated sequences of bacterial chromosomes, plasmids, phages and viruses, and in raw DNA sequences prior to annotation by comparing local and global OU patterns. The applet allows fast and reliable identification of clusters of horizontally transferred genomic islands, large multi-domain genes and genes for ribosomal RNA. Within the majority of genomic fragments (also termed genomic core sequence), regions enriched with housekeeping genes, ribosomal proteins and the regions rich in pseudogenes or genetic vestiges may be contrasted.</p> <p>Conclusion</p> <p>The SWGB applet presents a range of comprehensive OU statistical parameters calculated for a range of bacterial species, plasmids and phages. It is available on the Internet at <url>http://www.bi.up.ac.za/SeqWord/mhhapplet.php</url>.</p
Resistance sniffer : an online tool for prediction of drug resistance patterns of Mycobacterium tuberculosis isolates using next generation sequencing data
The effective control of multidrug resistant tuberculosis (MDR-TB) relies upon the timely diagnosis and correct
treatment of all tuberculosis cases. Whole genome sequencing (WGS) has great potential as a method for the
rapid diagnosis of drug resistant Mycobacterium tuberculosis (Mtb) isolates. This method overcomes most of the
problems that are associated with current phenotypic drug susceptibility testing. However, the application of
WGS in the clinical setting has been deterred by data complexities and skill requirements for implementing the
technologies as well as clinical interpretation of the next generation sequencing (NGS) data. The proposed diagnostic
application was drawn upon recent discoveries of patterns of Mtb clade-specific genetic polymorphisms
associated with antibiotic resistance. A catalogue of genetic determinants of resistance to thirteen anti-TB drugs
for each phylogenetic clade was created. A computational algorithm for the identification of states of diagnostic
polymorphisms was implemented as an online software tool, Resistance Sniffer (http://resistance-sniffer.bi.up.
ac.za/), and as a stand-alone software tool to predict drug resistance in Mtb isolates using complete or partial
genome datasets in different file formats including raw Illumina fastq read files. The program was validated on
sequenced Mtb isolates with data on antibiotic resistance trials available from GMTV database and from the TB
Platform of South African Medical Research Council (SAMRC), Pretoria. The program proved to be suitable for
probabilistic prediction of drug resistance profiles of individual strains and large sequence data sets.The South African National Research Foundation (NRF)https://www.elsevier.com/locate/ijmmam2020BiochemistryGeneticsMicrobiology and Plant Patholog
Does the applicability of Bacillus strains in probiotics rely upon their taxonomy?
The taxonomic position and biological activities of two Bacillus strains used in veterinary
probiotics were studied in this work. These microorganisms inhibit growth of a broad spectrum
of pathogenic cultures. They synthesize proteolytic enzymes and other biologically active
metabolites, and to some extent, supplement each other with probiotic activities. It is not clear
whether these versatile activities are properties of individual strains or bacterial taxa as whole.
16S rRNA comparisons were conducted and illustrated the relatedness of these strains to Bacillus
amyloliquefaciens. Their cell wall fatty acid contents were consequently analysed and specified a relation to the ‘B. velezensis’ ecomorph. On account of the previous observations, a simple
method of 16S rRNA profiling by polymorphic nucleotides was proposed to determine a group
of organisms closely related to ‘B. velezensis’ and B. amyloliquefaciens ssp. plantarum, for they
are biologically active strains suitable for use in biotechnology. The extreme genetic plasticity of
these bacteria endowed each strain with a unique spectrum of antagonistic activity.National Research Foundation (NRF) of South Africa by the MetaLingvo grant 71261.http://www.nrcresearchpress.com/journal/cjmnf201
Mupirocin promotes wound healing by stimulating growth factor production and proliferation of human keratinocytes
Mupirocin has been reported for its role in the treatment of infected wounds through its
antibacterial activity, however the role of mupirocin in promoting wound healing via
alternative mechanisms has not been extensively evaluated. This study aimed to
evaluate the potential effect of mupirocin to promote wound healing, not only through
its antibacterial activity but by increasing human keratinocyte proliferation and growth
factor production. In the scratch assay, using human keratinocytes (HaCat), mupirocin (at
0.1 and 0.2 mM) significantly increased wound closure compared to the vehicle control.
Cell viability, measured from the scratch assay, verified the increase in wound closure,
where mupirocin at both concentrations showed higher cell viability compared to the
vehicle control. In addition, mupirocin at 0.1 mM significantly stimulated the production of
hepatocyte growth factor and M-CSF in HaCat cells, whereas at 0.2 mM, PDGF-AA and
EPO were increased. The findings of this study suggest that mupirocin, which is commonly
used as an antibacterial agent for the treatment of wounds, also facilitates the wound
healing process by stimulating the proliferation of human keratinocytes and enhancing the
production of several growth factors involved in wound healing. This is the first report on
the effect of mupirocin on growth factors expressed by human keratinocytes as well as the
stimulation of keratinocyte proliferation.The National Research Foundation and Department of Science
Innovation South African Research Chairs Initiative (SARChI).https://www.frontiersin.org/journals/pharmacologydm2022BiochemistryGeneticsMicrobiology and Plant PathologyPlant Production and Soil Scienc
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