title: Comparison of transposon and deletion mutants in Mycobacterium tuberculosis: The case of rv1248c, encoding 2-hydroxy-3-oxoadipate synthase.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Maksymiuk
authors.affiliation: Department of Computer Science and Engineering, Texas A&M University, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ioerger
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Ruslana
authors.initials: R
authors.lastname: Bryk
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Kyu
authors.initials: K
authors.lastname: Rhee
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, USA.
authors.forename: James
authors.initials: J
authors.lastname: Sacchettini
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: cnathan@med.cornell.edu.
authors.forename: Carl
authors.initials: C
authors.lastname: Nathan
mesh_terms: D019880:Aldehyde-Ketone Transferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D005838:Genotype; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D010641:Phenotype; D017384:Sequence Deletion; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D019880:Aldehyde-Ketone Transferases; C021414:2-hydroxy-3-oxoadipate synthase
keywords: CDC1551; Genetic complementation; Hyroxyoxoadipate synthase; Transposon mutagenesis; Whole genome sequencing