Linked Life Data

15668009

Source:http://linkedlifedata.com/resource/pubmed/id/15668009

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-25
pubmed:abstractText
Tolerance to antimicrobial agents is a universal phenomenon in bacteria which are no longer multiplying or whose growth rate slows. Since slowly multiplying bacteria occur in clinical infections, extended periods of antimicrobial chemotherapy are needed to eradicate these organisms and to achieve cure. In this study, the molecular basis of antibiotic tolerance was investigated using transposon mutagenesis. We screened 5000 Escherichia coli Tn10Cam mutants for reduction of kanamycin tolerance in late stationary phase and found that 4935 mutants were able to grow to late stationary phase. Reduced tolerance was observed in nine mutants which became sensitive to killing by kanamycin. The mutant KS639 was the most sensitive one to kanamycin, and its genome was disrupted in an intergenic region which lies between aldB and yiaW open reading frames. This mutant showed increased sensitivity not only to kanamycin but also to gentamicin, ciprofloxacin and rifampicin. Reduced tolerance of KS639 to kanamycin was also observed in a murine thigh infection model. P1 transduction to the wild type strains confirmed that the intergenic region was responsible for the tolerance of the bacterium to antibiotics. Using PCR-directed one-step gene replacement, we inactivated the genes aldB, yiaW and yiaV. We also deleted the intergenic region. There was no difference in kanamycin tolerance between each mutant (DeltaaldB, DeltayiaW and DeltayiaV) and the parental strain. But the mutant lacking the intergenic region showed reduced tolerance to kanamycin. These data suggest that the intergenic region between aldB and yiaW genes may be involved in tolerance to antimicrobial agents in E. coli. Furthermore, they show that it is important in murine infection during antibiotic treatment and lead to a faster kill of the mutant bacteria.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0378-1097
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
243
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-24
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Transposon mutagenesis identifies genes which control antimicrobial drug tolerance in stationary-phase Escherichia coli.
pubmed:affiliation
Department of Medical Microbiology, St. George's Hospital Medical School, London SW17 ORE, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't