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Carbohydrate mimetics for Staphylococcus aureus capsule
Author(s) -
Fagan Diana Lee,
Vicarel Monica L.,
Alhassan AbdulBasit,
Norris Peter
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a766-d
Subject(s) - staphylococcus aureus , microbiology and biotechnology , trypsinization , capsule , bacteria , bacterial capsule , monoclonal antibody , carbohydrate , virulence , antibody , antibiotics , chemistry , immune system , enzyme , biology , biochemistry , immunology , trypsin , genetics , botany , gene
There is a need for new treatment methods for antibiotic‐resistant S. aureus . Capsule production appears to be an important virulence determinant, as capsular types 5 and 8 account for 75–90% of hospital‐acquired infections and anti‐capsular antibodies decrease mortality following S. aureus infections in mice. S. aureus vaccines may prove effective before surgery, but are less promising for patients with acute infections or a weakened immune response. Important advances in understanding the enzymatic pathways used to make the capsular polymers make capsular biosynthesis a viable target for disruption with carbohydrate mimics. To measure capsule production, monoclonal antibodies were produced against S. aureus , type 5. MAb SM.T5.B2.A12.C9 was shown to bind to type 5 purified capsular carbohydrate (but not to type 8). An ELISA was developed to test the effect of carbohydrate mimics on capsule synthesis. Bacteria were incubated with carbohydrate mimics overnight, then formalinized and trypsinized prior to use in the ELISA. Treatment of bacteria with MV‐II‐065 ( N ‐glucosyl 1,2,3‐triazole) significantly decreased (50–75%) capsule production by the bacteria. Preliminary studies with AB‐5‐83 (analog of L‐FucNAc) also indicated inhibition of capsule synthesis (60–80%). Effective compounds will be used to determine the importance of capsule production for virulence. Support: NIH R15 2003–2006, YSU PACER.