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Carbohydrate mimetics as potential antiinfective treatments for Staphylococcus aureus
Author(s) -
Fagan Diana L.,
Royal Maurice,
Vicarel Monica,
Norris Peter
Publication year - 2008
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.22.1_supplement.859.20
Subject(s) - staphylococcus aureus , microbiology and biotechnology , trypsinization , bacteria , incubation , bacterial capsule , antibody , antibiotics , monoclonal antibody , capsule , chemistry , virulence , biology , enzyme , biochemistry , immunology , trypsin , genetics , botany , gene
Antibiotic resistant strains of Staphylococcus aureus are an important cause of nosocomial infections. These strains are currently causing community‐acquired infections, resulting in an increased need for alternative therapies. S. aureus capsules appear to act as important virulence determinants, as bacteria with type 5 and 8 capsules cause 75–90% of nosocomial infections and anti‐capsular antibodies decrease mortality in infected mice. Our research involves construction of analogs of the aminosugars found in S. aureus capsules that we are testing for their ability to prevent capsule synthesis. To measure capsule production, bacteria were incubated with MV‐II‐065 or MV‐II‐063 (both n‐glucosyl 1,2,3‐triazoles with different functional groups), formalinized, trypsinized, and the bacteria used as an antigen in an ELISA. The presence of capsular carbohydrate was determined by incubation with anti‐capsular monoclonal antibodies, followed by a secondary incubation with peroxidase‐conjugate anti‐mouse Ig and a colorimetric substrate. Incubation type 5 S. Aureus with MV‐II‐065 decreased antibody binding, but the compound had no effect on Type 8 capsule synthesis. Studies with MV‐II‐063 (shown below) have indicated inhibition of capsule synthesis in Type 8 bacteria, while type 5 capsule synthesis remains to be tested. In addition to their possible therapeutic potential, the differential effects of these two compounds may be used to investigate the synthetic pathways for these capsules. Support: NIH R15 2003‐2006, YSU PACER.