Genetic approach to study the relationship between penicillin-binding protein 3 mutations and Haemophilus influenzae beta-lactam resistance by using site-directed mutagenesis and gene recombinants.

ABSTRACT: To clarify the relationship between mutations commonly found for penicillin-binding protein 3 (PBP 3) of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae isolates and beta-lactam resistance, single and multiple amino acid mutations at positions 377, 385, 389, 517, and 526 were introduced into PBP 3 of a beta-lactam-susceptible Rd strain by site-directed mutagenesis. Twelve isogenic recombinant strains were challenged with nine beta-lactam antibiotics. Replacement of the asparagine at position 526 with lysine (N526K) increased the resistance to imipenem eightfold and increased the resistance to various cephalosporins two- to eightfold. Substitution of threonine for serine at position 385 (S385T) and/or substitution of phenylalanine for leucine at position 389

SUBMITTER: Osaki Y 

PROVIDER: S-EPMC1168665 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature