PMID- 21041497
OWN - NLM
STAT- MEDLINE
DCOM- 20110125
LR  - 20220318
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 79
IP  - 1
DP  - 2011 Jan
TI  - Genome-wide identification of Streptococcus pneumoniae genes essential for 
      bacterial replication during experimental meningitis.
PG  - 288-97
LID - 10.1128/IAI.00631-10 [doi]
AB  - Meningitis is the most serious of invasive infections caused by the Gram-positive 
      bacterium Streptococcus pneumoniae. Vaccines protect only against a limited 
      number of serotypes, and evolving bacterial resistance to antimicrobials impedes 
      treatment. Further insight into the molecular pathogenesis of invasive 
      pneumococcal disease is required in order to enable the development of new or 
      adjunctive treatments and/or pneumococcal vaccines that are efficient across 
      serotypes. We applied genomic array footprinting (GAF) in the search for S. 
      pneumoniae genes that are essential during experimental meningitis. A total of 
      6,000 independent TIGR4 marinerT7 transposon mutants distributed over four 
      libraries were injected intracisternally into rabbits, and cerebrospinal fluid 
      (CSF) was collected after 3, 9, and 15 h. Microarray analysis of mutant-specific 
      probes from CSF samples and inocula identified 82 and 11 genes mutants of which 
      had become attenuated or enriched, respectively, during infection. The results 
      point to essential roles for capsular polysaccharides, nutrient uptake, and amino 
      acid biosynthesis in bacterial replication during experimental meningitis. The 
      GAF phenotype of a subset of identified targets was followed up by detailed 
      studies of directed mutants in competitive and noncompetitive infection models of 
      experimental rat meningitis. It appeared that adenylosuccinate synthetase, 
      flavodoxin, and LivJ, the substrate binding protein of a branched-chain amino 
      acid ABC transporter, are relevant as targets for future therapy and prevention 
      of pneumococcal meningitis, since their mutants were attenuated in both models of 
      infection as well as in competitive growth in human cerebrospinal fluid in vitro.
FAU - Molzen, T E
AU  - Molzen TE
AD  - Department of Clinical Microbiology, Copenhagen University Hospital, Herlev 
      Ringvej 75, 2730 Herlev, Denmark. molzen@dadlnet.dk
FAU - Burghout, P
AU  - Burghout P
FAU - Bootsma, H J
AU  - Bootsma HJ
FAU - Brandt, C T
AU  - Brandt CT
FAU - van der Gaast-de Jongh, Christa E
AU  - van der Gaast-de Jongh CE
FAU - Eleveld, M J
AU  - Eleveld MJ
FAU - Verbeek, M M
AU  - Verbeek MM
FAU - Frimodt-Moller, N
AU  - Frimodt-Moller N
FAU - Ostergaard, C
AU  - Ostergaard C
FAU - Hermans, P W M
AU  - Hermans PW
LA  - eng
SI  - GEO/GSE21729
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101101
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Bacterial Proteins)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/genetics/*metabolism
MH  - *Cell Division
MH  - Gene Expression Regulation, Bacterial/physiology
MH  - Gene Library
MH  - *Genome, Bacterial
MH  - Meningitis, Pneumococcal/*microbiology
MH  - Mutation
MH  - Rabbits
MH  - Rats
MH  - Streptococcus pneumoniae/*cytology/*genetics
PMC - PMC3019918
EDAT- 2010/11/03 06:00
MHDA- 2011/01/28 06:00
PMCR- 2011/07/01
CRDT- 2010/11/03 06:00
PHST- 2010/11/03 06:00 [entrez]
PHST- 2010/11/03 06:00 [pubmed]
PHST- 2011/01/28 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - IAI.00631-10 [pii]
AID - 0631-10 [pii]
AID - 10.1128/IAI.00631-10 [doi]
PST - ppublish
SO  - Infect Immun. 2011 Jan;79(1):288-97. doi: 10.1128/IAI.00631-10. Epub 2010 Nov 1.