Comparison of transposon and deletion mutants in Mycobacterium tuberculosis: The case of rv1248c, encoding 2-hydroxy-3-oxoadipate synthase

详细信息    查看全文

• 作者：Christina Maksymiuk^a ; ¹ ; Thomas Ioerger^b ; ¹ ; Anand Balakrishnan^a ; Ruslana Bryk^a ; Kyu Rhee^c ; James Sacchettini^d ; Carl Nathan^a ; ^{cnathan@med.cornell.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Genetic complementation ; Whole genome sequencing ; Transposon mutagenesis ; CDC1551 ; Hyroxyoxoadipate synthase
• 刊名：Tuberculosis
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：95
• 期：6
• 页码：689-694
• 全文大小：750 K

文摘

We compared phenotypes of five strains of Mycobacterium tuberculosis (Mtb) differing in their expression of rv1248c and its product, 2-hydroxy-3-oxoadipate synthase (HOAS), with a focus on carbon source-dependent growth rates and attenuation in mice. Surprisingly, an rv1248c transposon mutant on a CDC1551 background grew differently than an rv1248c deletion mutant on the same background. Moreover, the same rv1248c deletion in two different yet genetically similar strain backgrounds (CDC1551 and H37Rv) gave different phenotypes, though each could be complemented. Whole genome re-sequencing did not provide an obvious explanation for these discrepancies. These observations offer a cautionary lesson about the strength of inference from complementation and sequence analysis, and commend consideration of more complex phenomena than usually contemplated in Mtb, such as epigenetic control.