Yamano Y, Nishikawa T, Komatsu Y
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
J Antimicrob Chemother. 1990 Aug;26(2):175-84. doi: 10.1093/jac/26.2.175.
Porin-deficient mutants of Pseudomonas aeruginosa PAO1 were selected by isolating latamoxef-resistant mutants following chemical mutagenesis. Highly latamoxef-resistant mutants had alterations in both the outer membrane proteins and penicillin-binding protein 3, a lethal target of latamoxef. Both of these alterations may be essential for cells to acquire high resistance to latamoxef. Many of the latamoxef-resistant mutants were also resistant to new quinolones and chloramphenicol. Resistance to these compounds was simultaneously co-transduced from one mutant into strain PAO1 when selection was made for transduction of ofloxacin resistance. Study of these transductants indicated that decreased amounts of outer membrane proteins C, D2, E1, and E2 lowered the outer membrane permeability and resulted in resistance. Three of these proteins were apparently identical to proteins previously reported to function as small pores. The results suggested that at least one of the four proteins was functioning as a porin for the antibacterial agents studied.
通过化学诱变分离出拉氧头孢抗性突变体，从而筛选出铜绿假单胞菌PAO1的孔蛋白缺陷型突变体。高拉氧头孢抗性突变体的外膜蛋白和青霉素结合蛋白3（拉氧头孢的致死靶点）均发生了改变。这两种改变对于细胞获得对拉氧头孢的高抗性可能都是必不可少的。许多拉氧头孢抗性突变体对新型喹诺酮类药物和氯霉素也具有抗性。当选择转导氧氟沙星抗性时，对这些化合物的抗性可同时从一个突变体共转导至菌株PAO1中。对这些转导子的研究表明，外膜蛋白C、D2、E1和E2数量的减少降低了外膜通透性并导致了抗性。其中三种蛋白显然与先前报道的作为小孔发挥作用的蛋白相同。结果表明，这四种蛋白中至少有一种作为所研究抗菌剂的孔蛋白发挥作用。
