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

I.根据rRNA基因内转录间隔区1和2(分别为ITS1和ITS2)的核苷酸序列变异，对从日本24个BALF分离的卡氏肺孢子虫(Pc)进行了基因分型。共发现11种ITS1和11种ITS2基因，其中2种为新基因，3种为新基因。ITS1和ITS2两种基因组合产生30种ITS基因，其中10种为本文新描述。在24例患者中，有16例在同一标本的ITS区域观察到两种或两种以上的基因型。我们的研究结果将有助于Pc感染的流行病学调查。II.我们检测了从日本分离的24例肺炎肺炎(PCP)患者的Pc的二氢翼酸合成酶(DHPS)基因突变。在24例患者中有6例(25.0%)发现DHPs基因在55位和/或57位氨基酸发生突变。在DHPS基因突变的患者中，联用新诺明治疗失败的几率高于携带野生型DHPS的患者(n=4[100%]对n=2[11.1%]；P=0.002)。因此，我们的结果提示DHPS突变可能是联用新诺明治疗PCP失败的原因之一。

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.