Alterations in high molecular mass penicillin-binding protein 1 associated with beta-lactam resistance in Shigella...

Beta-lactam resistance poses a major problem in the chemotherapy of shigellosis caused by Shigella dysenteriae. Such resistance may arise from alterations in the affinities or amounts of the penicillin-binding proteins (PBPs) for beta-lactams, elaboration of beta-lactamases and reduced permeability across the outer membrane. The mechanisms of resistance in S. dysenteriae have not been studied in depth. This report describes a laboratory mutant, M19 which was characterized by the appearance of two high molecular mass PBPs of 84 (PBP1') and 82 kDa (PBP1"). M19 was more resistant to cefsulodin and cefoxitin. Resistance could be correlated with lower second order rate constants (k+2/K) of acylation. Moreover there was an overall two-fold increase in the relative amount of PBP1 (i.e. 1' + 1") in the mutant M19 compared to C152. This is the first report which presents evidence of the involvement of altered high molecular mass PBPs in beta-lactam resistance in S. dysenteriae.