Gilleland L B, Gilleland H E, Gibson J A, Champlin F R
Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
J Med Microbiol. 1989 May;29(1):41-50. doi: 10.1099/00222615-29-1-41.
Aminoglycoside-resistant variants of Pseudomonas aeruginosa strain PAO1 were readily selected by culturing the organism in medium containing increasing concentrations of gentamicin, tobramycin or amikacin until the strains were growing in a concentration of drug 128-fold greater than the minimal inhibitory concentration for the sensitive parent strain. These resistant strains exhibited characteristics previously associated with the impermeability type of resistance mechanism, i.e., they grew more slowly than the parent strain, the resistance was unstable in the absence of the antibiotic, and adaptation to one of the antibiotics conferred cross-resistance to other aminoglycosides. The adapted strains grew, with minimal morphological alterations, in concentrations of the various aminoglycosides that normally produced cell envelope damage, misshapen and filamentous cell formation, and cell lysis in the sensitive strain. Neither protein H1 nor phospholipid alterations appear to play a significant role in adaptive resistance to aminoglycoside antibiotics in this model system. The acquisition of adaptive resistance to the aminoglycoside antibiotics did not confer resistance to polymyxin B, another cationic antibiotic which is thought to share binding sites within the outer membrane with the aminoglycosides.
通过在含有浓度不断增加的庆大霉素、妥布霉素或阿米卡星的培养基中培养铜绿假单胞菌PAO1菌株，很容易筛选出对氨基糖苷类抗生素耐药的变异菌株，直至这些菌株能在比敏感亲本菌株的最低抑菌浓度高128倍的药物浓度中生长。这些耐药菌株表现出以前与通透性耐药机制相关的特征，即它们的生长速度比亲本菌株慢，在没有抗生素的情况下耐药性不稳定，并且对一种抗生素的适应会导致对其他氨基糖苷类抗生素产生交叉耐药性。适应后的菌株在各种氨基糖苷类抗生素的浓度下生长，形态改变极小，而这些浓度的抗生素在敏感菌株中通常会导致细胞包膜损伤、细胞畸形和丝状形成以及细胞裂解。在这个模型系统中，蛋白质H1和磷脂的改变似乎都没有在对氨基糖苷类抗生素的适应性耐药中发挥重要作用。获得对氨基糖苷类抗生素的适应性耐药并没有使菌株对多粘菌素B产生耐药性，多粘菌素B是另一种阳离子抗生素，被认为与氨基糖苷类抗生素在外膜内共享结合位点。
