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A genomic analysis of two‐component signal transduction in Streptococcus pneumoniae
Author(s) -
Throup John P.,
Koretke Kristin K.,
Bryant Alexander P.,
Ingraham Karen A.,
Chalker Alison F.,
Ge Yigong,
Marra Andrea,
Wallis Nicola G.,
Brown James R.,
Holmes David J.,
Rosenberg Martin,
Burnham Martin K. R.
Publication year - 2000
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2000.01725.x
Subject(s) - biology , response regulator , histidine kinase , streptococcus pneumoniae , genetics , orfs , two component regulatory system , signal transduction , gene , transduction (biophysics) , open reading frame , bacillus subtilis , microbiology and biotechnology , computational biology , mutant , peptide sequence , biochemistry , bacteria
A genomics‐based approach was used to identify the entire gene complement of putative two‐component signal transduction systems (TCSTSs) in Streptococcus pneumoniae . A total of 14 open reading frames (ORFs) were identified as putative response regulators, 13 of which were adjacent to genes encoding probable histidine kinases. Both the histidine kinase and response regulator proteins were categorized into subfamilies on the basis of phylogeny. Through a systematic programme of mutagenesis, the importance of each novel TCSTS was determined with respect to viability and pathogenicity. One TCSTS was identified that was essential for the growth of S. pneumoniae This locus was highly homologous to the yycFG gene pair encoding the essential response regulator/histidine kinase proteins identified in Bacillus subtilis and Staphylococcus aureus . Separate deletions of eight other loci led in each case to a dramatic attenuation of growth in a mouse respiratory tract infection model, suggesting that these signal transduction systems are important for the in vivo adaptation and pathogenesis of S. pneumoniae . The identification of conserved TCSTSs important for both pathogenicity and viability in a Gram‐positive pathogen highlights the potential of two‐component signal transduction as a multicomponent target for antibacterial drug discovery.