Pneumocystis jiroveci isolates with dihydropteroate synthase mutations in patients with chronic bronchitis

Pneumocystis jiroveci isolates with dihydropteroate synthase mutations in patients with chronic bronchitis
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DOI:
10.1007/s10096-004-1151-3
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发表时间:
2004-07-01
影响因子:
4.5
通讯作者:
Varela, JM
Varela, JM
中科院分区:
医学3区
文献类型:
--
作者:
Calderón, E;de la Horra, C;Varela, JM

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由于二氢蝶酸合成酶(DHPS)基因突变可能与磺胺耐药有关,已报道在耶氏肺囊虫(以前是卡氏)肺炎患者中,并且耶氏肺囊虫定植于慢性肺部疾病患者中最近被证实,本研究旨在调查耶氏肺囊虫DHPS突变在慢性支气管炎患者中的可能发生。通过巢式PCR扩增核糖体RNA线粒体基因大亚基,在37例非选择性慢性支气管炎患者中检测到15例吉罗氏疟原虫定植。通过触地PCR和限制性内切酶分析,在8名慢性支气管炎患者中的2名和来自同一地区的6名患有艾滋病相关肺囊虫肺炎的患者中的2名中证实了DHPS突变。在所有病例中,突变均发生在先前未接触过磺胺类药物的受试者中。这些数据可能对公共卫生具有重要意义,因为(i)氏疟原虫定植可加速慢性支气管炎的进展,(ii)这些患者通常是痰生产者,可能是磺胺耐药菌株的储存库,具有将其传播给易感染肺囊虫肺炎的免疫功能低下宿主的潜在能力。
Since mutations in the dihydropteroate synthase (DHPS) gene possibly associated with sulfonamide resistance have been reported in patients with Pneumocystis jiroveci (previously carinii) pneumonia, and since P. jiroveci colonization has been recently demonstrated in patients with chronic pulmonary diseases, the present study aimed to investigate the possible occurrence of P. jiroveci DHPS mutations in patients with chronic bronchitis. P. jiroveci colonization was detected in 15 of 37 non-selected patients with chronic bronchitis by amplifying the large subunit of the mitochondrial gene of the ribosomal RNA using nested PCR. DHPS mutations were demonstrated using touchdown PCR and restriction enzyme analysis in two of eight patients with chronic bronchitis and in two of six patients from the same region who had AIDS-associated Pneumocystis pneumonia. In all cases, mutations were observed in subjects with no prior exposure to sulfonamides. These data could have important implications for public health, since (i) P. jiroveci colonization could speed the progression of chronic bronchitis, and (ii) these patients, who are customary sputum producers, could represent a reservoir for sulfonamide-resistant strains with the potential ability to transmit them to immunocompromised hosts susceptible to Pneumocystis pneumonia.