Linked Life Data

15790069

Source:http://linkedlifedata.com/resource/pubmed/id/15790069

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-3-25
pubmed:abstractText
A collection of laboratory mutants and clinical MRSA strains, additionally exhibiting resistance to glycopeptide antibiotics, was studied in detail. The nature of resistance to glycopeptides was found to be different from that existing in vancomycin resistant (VR) enterococci. The mutants produced abnormal murein in which the level of highly oligomeric muropeptides was drastically reduced. Biochemical and genetic analyses of Penicillin Binding Proteins (PBPs) showed inactivation of PBP4. Changes in other PBPs were not apparent, except for PBP2a that was inactivated in the highly VR mutant VM. Transposon inactivation of the pbpB gene and several other genes involved in synthesis of staphylococcal peptidoglycan all caused dramatic reduction of glycopeptide resistance in the staphylococcal mutants. While inactivation of PBP2a slightly increased the levels of glycopeptide resistance, a combination of vancomycin or teicoplanin with beta-lactam inhibitors, chosen on the basis of their relatively selective affinities for individual staphylococcal PBPs completely inhibited the expression of glycopeptide resistance in MRSA. Glycopeptide antibiotics caused a virtually complete inhibition of cell wall turnover and autolysis and massive overgrowth of cell wall material in the glycopeptide resistant mutants. Bacteria were able to remove quantitatively glycopeptide molecules from the growth medium, and sequestered antibiotic could be recovered in biologically active form from the purified cell walls. These observations and the results of the vancomycin binding studies suggest alterations in the structural organization of the mutants' cell wall such that access of glycopeptide molecules to the sites of wall biosynthesis is blocked by steric hindrance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1733-1331
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
207-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Mechanism of vancomycin resistance in methicillin resistant Staphylococcus aureus.
pubmed:affiliation
Rockefeller University, 1230 York Ave, 10021 New York, NY, USA. sieradk@mail.rockefeller.edu
pubmed:publicationType
Journal Article