Mpiga Philomene, Ravaoarinoro Madeleine
Department of Clinical Microbiology, Centre Hospitalier de l'Université de Montréal (CHUM)-Hôtel-Dieu, 3850 St-Urbain, Room 5-206, Montréal, QC, Canada H2W 1T7.
Int J Antimicrob Agents. 2006 Apr;27(4):316-24. doi: 10.1016/j.ijantimicag.2005.11.010. Epub 2006 Mar 9.
Chlamydia trachomatis is a human pathogen that causes multiple diseases worldwide. Despite appropriate therapy with existing antichlamydial antibiotics, chronic exacerbated diseases often occur and lead to serious sequelae. Since C. trachomatis has been found to enter a persistent state after exposure to deleterious conditions, the role of persistence in the failure of chlamydial antibiotherapy is questioned. HeLa, THP-1 and U-937 cells were infected with 10(4)C. trachomatis serovar L2 infectious particles. Three days later the infected cells were treated with minimal bactericidal concentrations of doxycycline (DOX), erythromycin (ERY) or tetracycline (TET) for 24 days or 30 days. Antibiotic efficacy was assessed by measuring chlamydial inclusions and infectious particles, by investigating the resumption of chlamydial growth after antibiotic removal and by testing Chlamydia viability using reverse transcriptase polymerase chain reaction targeting unprocessed 16S rRNA, processed 16S rRNA and Omp-1 mRNA. Treatment of infected HeLa cells with the usual antichlamydial antibiotics suppressed chlamydial active growth. The infection remained unapparent. However, 24 days post treatment the bacterium was found to be viable, as proved by continued expression of unprocessed and processed 16S rRNA and Omp-1 mRNA. This inactive unapparent chlamydial state is not infectious, suggesting Chlamydia persistence. Chlamydia trachomatis also developed persistence both in permissive THP-1 and non-permissive U-937 cells. Unlike in HeLa cells, persistent chlamydial infection in THP-1 and U-937 cells was resolved after 30 days of DOX treatment. Of interest, we noticed that only THP-1 and U-937 cells that were persistently infected following their interaction with infected HeLa cells remained capable of transmitting active infection to HeLa cells. These findings suggest that DOX, TET and ERY, usually administered to combat chlamydial diseases, fail to resolve persistent infection occurring during treatment in non-immune HeLa cells. However, in immune THP-1 and U-937 cells, the persistent infection is resolved by therapy with DOX. Epithelial cells could be the reservoir of persistent chlamydial particles.
沙眼衣原体是一种在全球范围内引发多种疾病的人类病原体。尽管使用现有的抗衣原体抗生素进行了适当治疗，但慢性加重疾病仍经常发生并导致严重后遗症。由于已发现沙眼衣原体在暴露于有害条件后会进入持续状态，因此持续性在衣原体抗微生物治疗失败中的作用受到质疑。用10⁴个沙眼衣原体血清型L2感染性颗粒感染HeLa细胞、THP - 1细胞和U - 937细胞。三天后，用最低杀菌浓度的强力霉素（DOX）、红霉素（ERY）或四环素（TET）处理感染细胞24天或30天。通过测量衣原体包涵体和感染性颗粒、研究抗生素去除后衣原体生长的恢复情况以及使用针对未加工的16S rRNA、加工后的16S rRNA和Omp - 1 mRNA的逆转录酶聚合酶链反应检测衣原体活力来评估抗生素疗效。用常用的抗衣原体抗生素处理感染的HeLa细胞可抑制衣原体的活跃生长。感染仍不明显。然而，治疗后24天发现细菌仍有活力，未加工和加工后的16S rRNA以及Omp - 1 mRNA的持续表达证明了这一点。这种无活性的不明显衣原体状态不具有传染性，提示衣原体持续性。沙眼衣原体在允许性的THP - 1细胞和非允许性的U - 937细胞中也会形成持续性感染。与HeLa细胞不同，DOX处理30天后，THP - 1细胞和U - 937细胞中的持续性衣原体感染得到解决。有趣的是，我们注意到只有在与感染的HeLa细胞相互作用后持续感染的THP - 1细胞和U - 937细胞仍能够将活跃感染传播给HeLa细胞。这些发现表明，通常用于对抗衣原体疾病的DOX、TET和ERY无法解决在非免疫性HeLa细胞治疗期间发生的持续性感染。然而，在免疫性的THP - 1细胞和U - 937细胞中，DOX治疗可解决持续性感染。上皮细胞可能是持续性衣原体颗粒的储存库。
