Frequency of spontaneous mutations that confer antibiotic resistance in Chlamydia spp.
Frequency of spontaneous mutations that confer antibiotic resistance in Chlamydia spp.
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DOI：
10.1128/aac.49.7.2865-2873.2005
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发表时间：
2005-07-01
影响因子：
4.9
通讯作者：
Maurelli, AT
中科院分区：
文献类型：
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作者：
Binet, R;Maurelli, AT
赋予对核糖体抑制剂抗性的 rRNA 基因 (rrn) 突变通常是隐性或弱共显性的，并且大多数报道是针对仅拥有一个或两个 rrn 操纵子的临床病原体菌株，例如幽门螺杆菌和分枝杆菌属。对衣原体科几个成员的基因组序列的分析表明，这些专性细胞内细菌仅含有一组或两组 rRNA 基因。为了研究 rRNA 突变对衣原体耐药性出现的影响，我们使用沙眼衣原体 L2（两个 rrn 操纵子）和鹦鹉热衣原体 6BC（一个 rrn 操纵子）对氨基糖苷类大观霉素的敏感性作为模型。在噬菌斑测定中，用大约 108 个野生型感染颗粒感染汇合的单层细胞，然后用抗生素处理。两周的孵育时间后，对于鹦鹉热衣原体6BC，自发壮观霉素抗性(Spc(r)) 突变体形成的噬斑出现频率为5 x 10(-5)。尽管两种菌株的利福平耐药频率在相同范围内（即 10(-7)），但没有分离出沙眼衣原体 L2 的 Spc(r) 突变体。讨论了对四环素和大环内酯类（目前用于治疗衣原体感染的核糖体药物）出现耐药的衣原体菌株的风险。
Mutations in rRNA genes (rrn) that confer resistance to ribosomal inhibitors are typically recessive or weakly codominant and have been mostly reported for clinical strains of pathogens possessing only one or two rrn operons, such as Helicobacterpylori and Mycobacterium spp. An analysis of the genome sequences of several members of the Chlamydiaceae revealed that these obligate intracellular bacteria harbor only one or two sets of rRNA genes. To study the contribution of rRNA mutations to the emergence of drug resistance in the Chlamydiaceae, we used the sensitivities of Chlainydia trachomatis L2 (two rrn operons) and Chlamydophila psittaci 6BC (one rrn operon) to the aminoglycoside spectinomycin as a model. Confluent cell monolayers were infected in a plaque assay with about 108 wild-type infectious particles and then treated with the antibiotic. After a 2-week incubation time, plaques formed by spontaneous spectinomycin-resistant (Spc(r)) mutants appeared with a frequency of 5 x 10(-5) for C. psittaci 6BC. No Spc(r) mutants were isolated for C. trachomatis L2, although the frequencies of rifampin resistance were in the same range for both strains (i.e., 10(-7)). The risk of emergence of Chlainydia strains resistant to tetracyclines and macrolides, the ribosomal drugs currently used to treat chlamydial infections, is discussed.