研究一株imipenem-resistant Proteus mirabilis的抗藥性機轉

Investigating the Antibiotic Resistant Mechanisms of a Strain of imipenem-resistant Proteus mirabilis

在南台灣的某區域醫院分離出一株imipenem-resistant Proteus mirabilis，此菌株因為imipenem的最低抑菌濃度＞32 mg/ml，屬於罕見菌株，我們利用分子生物學方法研究其抗藥性機轉。此菌株具有一條可自我轉移的IncA/C質體，並且攜帶有blaCMY-2及aac(6')-Ib-cr兩種抗藥基因。原本敏感性的Escherichia coli J53在接受這條抗藥性質體後，呈現出對b-lactams、aminoglycosides、以及ciprofloxacin的抗藥性，但對imipenem仍然保持敏感性。進一步分析外膜蛋白的結果顯示，OmpF發生插入式突變，在第321與322個胺基酸之間，多了Cysteine與Serine兩個胺基酸。在另一個44 KD的外膜蛋白，則是在第78個胺基酸的位置發生取代性突變，由Isoleucine變成Threonine。抗藥性基因blaCMY-2的存在合併外膜蛋白的變異，可能就是此一研究菌株對imipenem表現抗藥性的原因。我們發現的這一條可以自我轉移的抗藥性質體，也代表著一個嚴重的問題，值得多加注意。 At a regional hospital in Southern Taiwan, a strain of imipenem-resistant Proteus mirabilis was isolated. With the high minimum inhibitory concentration (＞32 g/ml) of imipenem, it was deemed as a rare strain and was subjected to molecular investigation. A 200-Kb IncA/C plasmid which carried both blaCMY-2 and aac(6')-Ib-cr genes was identified. The resistance plasmid was also found to be conjugative. Its introduction in Escherichia coli J53 led to the observed resistance to -lactams, aminoglycosides, and ciprofloxacin, but not the imipenem resistance. Outer membrane protein (OMP) analysis revealed an insertional mutation of two extra amino acids, Cysteine and Serine, at the position between amino acids 321-322 in OmpF. In another 44KD OMP, one substitutional mutation from Isoleucine to Threonine was found at amino acid 78. The presence of blaCMY-2 and OMP defects may together contribute to the imipenem resistance in the study strain. The self-transferrable resistance plasmid may represent an important problem that deserves more attention.