2026-04-29T04:09:04Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/72012025-05-27T12:13:23Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Martin-Galiano, Antonio Javier
author
Yuste, Jose Enrique
author
Cercenado, Maria I
author
de la Campa, Adela G
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
2019-02-20T13:54:25Z
2019-02-20T13:54:25Z
2014-08-05
BMC Genomics. 2014 Aug 5;15:652.
1471-2164
http://hdl.handle.net/20.500.12105/7201
25096389
10.1186/1471-2164-15-652
BMC genomics
BACKGROUND: 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.
eng
Antibiotic target
Bacterial pathogenesis
Hypothetical protein
Post-genomics
Protein function
Proteinspace
Proteomics
Virulence factors
Inspecting the potential physiological and biomedical value of 44 conserved uncharacterised proteins of Streptococcus pneumoniae
research article
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InspectingTheOotentialPhysiological_2014.pdf
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InspectingTheOotentialPhysiological_2014.pdf.txt