Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-3-26
pubmed:abstractText
Attempted allelic replacement of 144 Streptococcus pneumoniae open reading frames of previously uncharacterized function led to the identification of 36 genes essential for growth under laboratory conditions. Of these, 14 genes (obg, spoIIIJ2, trmU, yacA, yacM, ydiC, ydiE, yjbN, yneS, yphC, ysxC, ytaG, yloI and yxeH4) were also essential in Staphylococcus aureus and Haemophilus influenzae or Escherichia coli, 2 genes (yrrK and ydiB) were only essential in H. influenzae as well as S. pneumoniae and 8 genes were necessary for growth of S.pneumoniae and S. aureus and did not have a homolog in H. influenzae(murD2, ykqC, ylqF, yqeH, ytgP, yybQ) or were not essential in that organism (yqeL, yhcT). The proteins encoded by these genes could represent good targets for novel antibiotics covering different therapeutic profiles. The putative functions of some of these essential proteins, inferred by bioinformatic analysis, are presented. Four mutants, with deletions of loci not essential for in vitro growth, were found to be severely attenuated in a murine respiratory tract infection model, suggesting that not all targets for antibacterial therapeutics are revealed by simple in vitro essentiality testing. The results of our experiments together with those collated from previously reported studies including Bacillus subtilis, E. coli and Mycoplasma sp. demonstrate that gene conservation amongst bacteria does not necessarily indicate that essentiality in one organism can be extrapolated to others. Moreover, this study demonstrates that different experimental procedures can produce apparently contradictory results.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1464-1801
pubmed:author
pubmed:copyrightInfo
Copyright 2003 S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-26
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:15044829-Alleles, pubmed-meshheading:15044829-Animals, pubmed-meshheading:15044829-Bacterial Proteins, pubmed-meshheading:15044829-Computational Biology, pubmed-meshheading:15044829-Disease Models, Animal, pubmed-meshheading:15044829-Gene Expression Regulation, Bacterial, pubmed-meshheading:15044829-Genes, Essential, pubmed-meshheading:15044829-Genome, Bacterial, pubmed-meshheading:15044829-Haemophilus influenzae, pubmed-meshheading:15044829-Humans, pubmed-meshheading:15044829-Male, pubmed-meshheading:15044829-Mice, pubmed-meshheading:15044829-Mice, Inbred CBA, pubmed-meshheading:15044829-Mutagenesis, pubmed-meshheading:15044829-Pneumonia, Pneumococcal, pubmed-meshheading:15044829-Pyelonephritis, pubmed-meshheading:15044829-Recombination, Genetic, pubmed-meshheading:15044829-Respiratory Tract Infections, pubmed-meshheading:15044829-Staphylococcal Infections, pubmed-meshheading:15044829-Staphylococcus aureus, pubmed-meshheading:15044829-Streptococcus pneumoniae
pubmed:year
2003
pubmed:articleTitle
A global approach to identify novel broad-spectrum antibacterial targets among proteins of unknown function.
pubmed:affiliation
Microbial, Musculoskeletal and Proliferative Diseases CEDD, Collegeville, PA 17426, USA. magdalena_zalacain-1@gsk.com
pubmed:publicationType
Journal Article, Evaluation Studies