Ghosh A S, Kar A K, Kundu M
Department of Chemistry, Bose Institute, Calcutta, India.
Biochem Biophys Res Commun. 1998 Jul 30;248(3):669-72. doi: 10.1006/bbrc.1998.9042.
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.
β-内酰胺耐药性是痢疾志贺氏菌引起的志贺氏菌病化疗中的一个主要问题。这种耐药性可能源于青霉素结合蛋白（PBPs）对β-内酰胺的亲和力或数量的改变、β-内酰胺酶的产生以及外膜通透性的降低。痢疾志贺氏菌的耐药机制尚未得到深入研究。本报告描述了一个实验室突变体M19，其特征是出现了两个高分子量的PBPs，分别为84 kDa（PBP1'）和82 kDa（PBP1"）。M19对头孢磺啶和头孢西丁的耐药性更强。耐药性可能与酰化反应的二级速率常数（k+2/K）较低有关。此外，与C152相比，突变体M19中PBP1（即1'+1"）的相对含量总体增加了两倍。这是第一份提出高分子量PBPs改变参与痢疾志贺氏菌β-内酰胺耐药性证据的报告。
