Möllmann U, Ghosh A, Dolence E K, Dolence J A, Ghosh M, Miller M J, Reissbrodt R
Hans-Knöll Institut für Naturstoff-Forschung, Jena, Germany.
Biometals. 1998 Jan;11(1):1-12. doi: 10.1023/a:1009266705308.
Conjugates of a carbacephalosporin with hydroxamate, spermexatol, N alpha,N epsilon-bis(2,3-dihydroxybenzoyl)-L-lysine, mixed catecholate/hydroxamate and cyanuric acid-based siderophores were investigated for their potential to promote growth of siderophore indicator strains of Gram-negative and Gram-positive bacteria under iron depleted conditions, for their antibacterial activity and for their ability to use iron transport pathways to penetrate the Gram-negative bacterial outer membrane. The selective growth promotion of enterobacterial and pseudomonas strains by hydroxamate, spermexatol and mixed catecholate-hydroxamate siderophore-based conjugates bearing a L- or D-amino acid spacer was correlated with TonB dependent uptake routes. The preferred outer membrane siderophore receptor used in Escherichia coli was found to be Fiu, followed by Cir. Antagonistic effects of siderophores administered with the conjugates to determine antibacterial activity confirmed the active transport of conjugates via siderophore receptors. All of the conjugates were still able to diffuse through the porin proteins OmpC and OmpF. Nevertheless, strong inhibition of E. coli and Pseudomones aeruginosa outer membrane mutants DC2 and K799/61 compared to the parent strains indicated inefficient penetrability of all types of conjugates tested. Mycobacterium smegmatis SG 987 was able to use all of the siderophore-cephalosporin conjugates as growth promotors. Consequently there was no growth inhibition of this strain.
研究了碳头孢菌素与异羟肟酸、精子外毒素、Nα，Nε-双（2,3-二羟基苯甲酰基）-L-赖氨酸、混合儿茶酚盐/异羟肟酸和基于氰尿酸的铁载体的缀合物，考察它们在缺铁条件下促进革兰氏阴性和革兰氏阳性细菌铁载体指示菌株生长的潜力、抗菌活性以及利用铁转运途径穿透革兰氏阴性细菌外膜的能力。带有L-或D-氨基酸间隔基的基于异羟肟酸、精子外毒素和混合儿茶酚盐-异羟肟酸铁载体的缀合物对肠杆菌和假单胞菌菌株的选择性生长促进作用与TonB依赖性摄取途径相关。发现大肠杆菌中使用的首选外膜铁载体受体是Fiu，其次是Cir。与缀合物一起施用的铁载体的拮抗作用以确定抗菌活性，证实了缀合物通过铁载体受体的主动转运。所有缀合物仍能够通过孔蛋白OmpC和OmpF扩散。然而，与亲本菌株相比，大肠杆菌和铜绿假单胞菌外膜突变体DC2和K799/61受到的强烈抑制表明，所测试的所有类型的缀合物的穿透效率低下。耻垢分枝杆菌SG 987能够将所有铁载体-头孢菌素缀合物用作生长促进剂。因此，该菌株没有生长抑制。
