A global approach to identify novel broad-spectrum antibacterial targets among proteins of unknown function
| Autor: | Alexander P. Bryant, Chi So, Serban Iordanescu, Sylvester Daniel R, Patrick Vernon Warren, David J. Holmes, James R. Brown, Jing Fan, Damien McDevitt, Craig Volker, Jennifer Ambrad, Leslie Marie Palmer, Sanjoy Biswas, Karen O'Dwyer, Frank Fan, Karen A. Ingraham, Magdalena Zalacain, R. Dwayne Lunsford, Martin Karl Russel Burnham, Alison F. Chalker |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Staphylococcus aureus Physiology Mutant Bacillus subtilis Biology medicine.disease_cause Applied Microbiology and Biotechnology Biochemistry Microbiology Haemophilus influenzae Mice Bacterial Proteins Streptococcus pneumoniae medicine Animals Humans Escherichia coli Gene Respiratory Tract Infections Alleles Genetics Recombination Genetic Genes Essential Pyelonephritis Computational Biology Cell Biology Gene Expression Regulation Bacterial Pneumonia Pneumococcal Staphylococcal Infections biology.organism_classification Open reading frame Disease Models Animal Mutagenesis Mice Inbred CBA Function (biology) Genome Bacterial Biotechnology |
| Zdroj: | Journal of molecular microbiology and biotechnology. 6(2) |
| ISSN: | 1464-1801 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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