Molecular Biological Study on Hospital-Acquired Infections and Drug-Resistance of Pneumocystis carinii

基于rRNA基因内部转录间隔区1和2（分别为ITS1和ITS2）的核苷酸序列变异，对日本24例BALF分离的卡氏肺囊虫（Pc）进行了基因分型检测。发现ITS1基因型11个，其中2个为新基因型；ITS2基因型11个，其中3个为新基因型。ITS1和ITS2基因型组合得到30个ITS基因型，其中10个为本文新报道。24例患者中有16例在标本中观察到ITS区域的两种或两种以上基因型。本研究结果对Pc感染的流行病学调查有一定的指导意义。2。我们检测了日本24例Pc肺炎（PCP）分离的Pc二氢蝶酸合成酶（DHPS）基因突变。在24例患者中的6例（25.0%）分离株中，在55和/或57个氨基酸位置发现了DHPS突变。DHPS突变株患者的复方新诺明治疗失败率高于DHPS野生型患者（n=4[100%]对n=2 [11.1%]； P=0.002）。因此，我们的研究结果表明，DHPS突变可能导致复方新诺明治疗PCP失败。

I.Genotyping of Pneumocystis carinii (Pc) isolated from 24 BALF in Japan was examined based on nucleotide sequence variations in internal transcribed spacer regions 1 and 2 (ITS1 and ITS2, respectively) of rRNA genes. We found 11 ITS1 genotypes including 2 novel ones and 11 ITS2 genotypes including 3 new ones. Combination of ITS1 and ITS2 genotypes resulted in 30 ITS genotypes, of which 10 were newly described in this report. Two or more genotypes in ITS regions in a specimen were observed in 16 of 24 patients. Our results will be of help for the epidemiological investigation of Pc infection. II.We examined mutations in dihydropteroate synthase (DHPS) gene of Pc isolated from 24 patients with Pc pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0 %) of 24 patients. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n=4 [100%] versus n=2 [11.1%] ; P=0.002). Our results thus suggest that DHPS mutations may contribute to failures of co-trimoxazole treatment for PCP.