Abstract
BackgroundThe 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.ResultsForty 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.ConclusionsUncharacterised 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-652) contains supplementary material, which is available to authorized users.
Highlights
The major Gram-positive coccoid pathogens cause similar invasive diseases and show high rates of antimicrobial resistance
In order to select Conserved hypothetical protein (cHP) of S. pneumoniae R6 that were truly uncharacterised and that were chemically amenable to experimental analysis, 858 potential cHPs were initially selected (Figure 1)
This paper reports an attempt to characterize the genes coding for cHPs in Gram-positive cocci using S. pneumoniae as a model organism
Summary
The major Gram-positive coccoid pathogens cause similar invasive diseases and show high rates of antimicrobial resistance. The roles of many of the proteins apparently involved in the pathobiology of Gram-positive cocci are poorly understood. This is true with respect to the transition from commensal to pathogenic status. A number of pathogens rely on the autolysis – sometimes non-fatal – of some of their population. This releases highly inflammatory fragments of cell wall and cytoplasmic virulence factors into host tissues, and frees other virulence factors, facilitating invasion by the population as a whole [8,9,10]
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