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Mosquera-Rendon J.,Bioinformatics Analysis Group GABi | Mosquera-Rendon J.,University of Antioquia | Rada-Bravo A.M.,University of Antioquia | Rada-Bravo A.M.,Major College of Antioquia | And 6 more authors.
BMC Genomics | Year: 2016

Background: Drug treatments and vaccine designs against the opportunistic human pathogen Pseudomonas aeruginosa have multiple issues, all associated with the diverse genetic traits present in this pathogen, ranging from multi-drug resistant genes to the molecular machinery for the biosynthesis of biofilms. Several candidate vaccines against P. aeruginosa have been developed, which target the outer membrane proteins; however, major issues arise when attempting to establish complete protection against this pathogen due to its presumably genotypic variation at the strain level. To shed light on this concern, we proposed this study to assess the P. aeruginosa pangenome and its molecular evolution across multiple strains. Results: The P. aeruginosa pangenome was estimated to contain more than 16,000 non-redundant genes, and approximately 15 % of these constituted the core genome. Functional analyses of the accessory genome indicated a wide presence of genetic elements directly associated with pathogenicity. An in-depth molecular evolution analysis revealed the full landscape of selection forces acting on the P. aeruginosa pangenome, in which purifying selection drives evolution in the genome of this human pathogen. We also detected distinctive positive selection in a wide variety of outer membrane proteins, with the data supporting the concept of substantial genetic variation in proteins probably recognized as antigens. Approaching the evolutionary information of genes under extremely positive selection, we designed a new Multi-Locus Sequencing Typing assay for an informative, rapid, and cost-effective genotyping of P. aeruginosa clinical isolates. Conclusions: We report the unprecedented pangenome characterization of P. aeruginosa on a large scale, which included almost 200 bacterial genomes from one single species and a molecular evolutionary analysis at the pangenome scale. Evolutionary information presented here provides a clear explanation of the issues associated with the use of protein conjugates from pili, flagella, or secretion systems as antigens for vaccine design, which exhibit high genetic variation in terms of non-synonymous substitutions in P. aeruginosa strains. © 2016 Mosquera-Rendón et al. Source


Benitez-Paez A.,Research Center y Desarrollo en Biotecnologia | Cardenas-Brito S.,Research Center y Desarrollo en Biotecnologia | Corredor M.,University of Antioquia | Villarroya M.,Research Center Principe Felipe | Armengod M.E.,Research Center Principe Felipe
Biomédica : revista del Instituto Nacional de Salud | Year: 2014

INTRODUCTION: Aminoglycosides like streptomycin are well-known for binding at specific regions of ribosome RNA and then acting as translation inhibitors. Nowadays, several pathogens have been detected to acquire an undefined strategy involving mutation at non structural ribosome genes like those acting as RNA methylases. rsmG is one of those genes which encodes an AdoMet-dependent methyltransferase responsible for the synthesis of m 7 G527 in the 530 loop of bacterial 16S rRNA. This loop is universally conserved, plays a key role in ribosomal accuracy, and is a target for streptomycin binding. Loss of the m 7 G527 modification confers low-level streptomycin resistance and may affect ribosomal functioning.OBJECTIVES: After taking into account genetic information indicating that some clinical isolates of human pathogens show streptomycin resistance associated with mutations at rsmG , we decided to explore new hot spots for mutation capable of impairing the RsmG in vivo function and of promoting low-level streptomycin resistance.MATERIALS AND METHODS: To gain insights into the molecular and genetic mechanism of acquiring this aminoglycoside resistance phenotype and the emergence of high-level streptomycin resistance in rsmG mutants, we mutated Escherichia coli rsmG and also performed a genotyping study on rpsL from several isolates showing the ability to grow at higher streptomycin concentrations than parental strains.RESULTS: We found that the mutations at rpsL were preferentially present in these mutants, and we observed a clear synergy between rsmG and rpsL genes to induce streptomycin resistance.CONCLUSION: We contribute to understand a common mechanism that is probably transferable to other ribosome RNA methylase genes responsible for modifications at central sites for ribosome function. Source


Benitez-Paez A.,Research Center y Desarrollo en Biotecnologia | Benitez-Paez A.,Research Center Principe Felipe | Cardenas-Brito S.,Research Center y Desarrollo en Biotecnologia | Corredor M.,Research Center y Desarrollo en Biotecnologia | And 3 more authors.
Biomedica | Year: 2014

Introduction: Aminoglycosides like streptomycin are well-known for binding at specific regions of ribosome RNA and then acting as translation inhibitors. Nowadays, several pathogens have been detected to acquire an undefined strategy involving mutation at non structural ribosome genes like those acting as RNA methylases. rsmG is one of those genes which encodes an AdoMet-dependent methyltransferase responsible for the synthesis of m7G527 in the 530 loop of bacterial 16S rRNA. This loop is universally conserved, plays a key role in ribosomal accuracy, and is a target for streptomycin binding. Loss of the m7G527 modification confers low-level streptomycin resistance and may affect ribosomal functioning. Objectives: After taking into account genetic information indicating that some clinical isolates of human pathogens show streptomycin resistance associated with mutations at rsmG, we decided to explore new hot spots for mutation capable of impairing the RsmG in vivo function and of promoting low-level streptomycin resistance. Materials and methods: To gain insights into the molecular and genetic mechanism of acquiring this aminoglycoside resistance phenotype and the emergence of high-level streptomycin resistance in rsmG mutants, we mutated Escherichia coli rsmG and also performed a genotyping study on rpsL from several isolates showing the ability to grow at higher streptomycin concentrations than parental strains. Results: We found that the mutations at rpsL were preferentially present in these mutants, and we observed a clear synergy between rsmG and rpsL genes to induce streptomycin resistance. Conclusion: We contribute to understand a common mechanism that is probably transferable to other ribosome RNA methylase genes responsible for modifications at central sites for ribosome function. Source


Benitez-Paez A.,Research Center y Desarrollo en Biotecnologia | Cardenas-Brito S.,Research Center y Desarrollo en Biotecnologia
Biomedica | Year: 2010

Bioinformatics emerged about 50 years ago, but it was developed greatly during the early 1980's by robust databases such as GenBank, EMBL, and DNA Database of Japan (DDBJ). Bioinformatic routines were rapidly adapted once the main algorithms for sequence analysis became available worldwide. As in other science fields, bioinformatics had minimal impact in low-income countries of Latin America until the last decade. We revised the bioinformatics state of art in Colombia and found a few bioinformatics groups carrying out basic computational biology research. Nowadays, bioinformatics in Colombia has a hopeful scenario thanks to recent science policies adopted by the Colombian Government. Such policies have been adopted in order to establish a new model of sustainable scientific research. In this brief report we revise the bioinformatics state of the art in Colombia. Finally, we conclude with some considerations for the proposed science model and we describe different perspectives of interest for the Colombian scientific community. Source


Munoz-Gomez A.,University of Antioquia | Munoz-Gomez A.,Research Center y Desarrollo en Biotecnologia | Corredor M.,University of Antioquia | Corredor M.,Research Center y Desarrollo en Biotecnologia | And 3 more authors.
Advances in Intelligent Systems and Computing | Year: 2014

Isobaric tags for relative and absolute quantification of protein expression (iTRAQ®) is a powerful tool which is combined with the accuracy of Mass Spectrometry for protein identification. This tool was approached to detect proteins associated to the innate immune system of Galleria mellonella in response to pathogenesis caused by Fusarium oxysporum. After experimental approaches, iTRAQ data was used to set up computational analysis based on identification and quantification of peptides and proteins against different protein databases by using ProteinPilot™ and Mascot Distiller search engines. iTRAQ battery was able to identify more than 340 peptides corresponding to 39 putative proteins from G. mellonella and close related species. Despite the low level of genomic and proteomic information available for G. mellonella, iTRAQ demonstrated to be reliable strategy to determine changes in protein expression as a consequence of the infection process induced in G. mellonella. Consequently, it was found differential expression in proteins directly involved in innate immune response such as cecropin-D-like peptide, lysozyme, and hemolin, indicating an active response of G. mellonella in early stages of fungal infection. © Springer International Publishing Switzerland 2014. Source

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