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dc.contributor.authorMartin-Galiano, Antonio Javier 
dc.contributor.authorYuste, Jose Enrique 
dc.contributor.authorCercenado, Maria I 
dc.contributor.authorde la Campa, Adela G
dc.identifier.citationBMC Genomics. 2014 Aug 5;15:652.es_ES
dc.description.abstractBACKGROUND: The major Gram-positive coccoid pathogens cause similar invasive diseases and show high rates of antimicrobial resistance. Uncharacterised proteins shared by these organisms may be involved in virulence or be targets for antimicrobial therapy. RESULTS: Forty four uncharacterised proteins from Streptococcus pneumoniae with homologues in Enterococcus faecalis and/or Staphylococcus aureus were selected for analysis. These proteins showed differences in terms of sequence conservation and number of interacting partners. Twenty eight of these proteins were monodomain proteins and 16 were modular, involving domain combinations and, in many cases, predicted unstructured regions. The genes coding for four of these 44 proteins were essential. Genomic and structural studies showed one of the four essential genes to code for a promising antibacterial target. The strongest impact of gene removal was on monodomain proteins showing high sequence conservation and/or interactions with many other proteins. Eleven out of 40 knockouts (one for each gene) showed growth delay and 10 knockouts presented a chaining phenotype. Five of these chaining mutants showed a lack of putative DNA-binding proteins. This suggest this phenotype results from a loss of overall transcription regulation. Five knockouts showed defective autolysis in response to penicillin and vancomycin, and attenuated virulence in an animal model of sepsis. CONCLUSIONS: Uncharacterised proteins make up a reservoir of polypeptides of different physiological importance and biomedical potential. A promising antibacterial target was identified. Five of the 44 examined proteins seemed to be virulence factors.es_ES
dc.description.sponsorshipThis work was supported by a Miguel Servet Research contract funded by the Fondo de Investigación Sanitaria (Ministerio de Economía y Competitividad de España) to Antonio J. Martin-Galiano, a Plan Nacional de I + D + I of Ministerio de Ciencia e Innovación grant (BIO2011-25343) to Adela G. de la Campa, and funds from the CIBER Enfermedades Respiratorias group (an initiative of the Instituto de Salud Carlos III).es_ES
dc.publisherBiomed Centrales_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectAntibiotic targetes_ES
dc.subjectBacterial pathogenesises_ES
dc.subjectHypothetical proteines_ES
dc.subjectProtein functiones_ES
dc.subjectVirulence factorses_ES
dc.subject.meshAnti-Bacterial Agents es_ES
dc.subject.meshBacterial Proteins es_ES
dc.subject.meshGene Knockout Techniques es_ES
dc.subject.meshPhenotype es_ES
dc.subject.meshProtein Structure, Tertiaryes_ES
dc.subject.meshSequence Homology, Amino Acid es_ES
dc.subject.meshStreptococcus pneumoniae es_ES
dc.subject.meshBiomedical Research es_ES
dc.subject.meshConserved Sequence es_ES
dc.titleInspecting the potential physiological and biomedical value of 44 conserved uncharacterised proteins of Streptococcus pneumoniaees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderFondo de Investigaciones Sanitariases_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.identifier.journalBMC genomicses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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Atribución 4.0 Internacional
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