Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster

Sivagami Sundaram Chavadi, Karen L. Stirrett, Uthamaphani R. Edupuganti, Olivia M. Vergnolle, Gigani Sadhanandan, Emily Marchiano, Che Martin, Wei Gang Qiu, Clifford E. Soll, Luis E N Quadri

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The mycobactin siderophore system is present in many Mycobacterium species, including M. tuberculosis and other clinically relevant mycobacteria. This siderophore system is believed to be utilized by both pathogenic and nonpathogenic mycobacteria for iron acquisition in both in vivo and ex vivo iron-limiting environments, respectively. Several M. tuberculosis genes located in a so-called mbt gene cluster have been predicted to be required for the biosynthesis of the core scaffold of mycobactin based on sequence analysis. A systematic and controlled mutational analysis probing the hypothesized essential nature of each of these genes for mycobactin production has been lacking. The degree of conservation of mbt gene cluster orthologs remains to be investigated as well. In this study, we sought to conclusively establish whether each of nine mbt genes was required for mycobactin production and to examine the conservation of gene clusters orthologous to the M. tuberculosis mbt gene cluster in other bacteria. We report a systematic mutational analysis of the mbt gene cluster ortholog found in Mycobacterium smegmatis. This mutational analysis demonstrates that eight of the nine mbt genes investigated are essential for mycobactin production. Our genome mining and phylogenetic analyses reveal the presence of orthologous mbt gene clusters in several bacterial species. These gene clusters display significant organizational differences originating from an intricate evolutionary path that might have included horizontal gene transfers. Altogether, the findings reported herein advance our understanding of the genetic requirements for the biosynthesis of an important mycobacterial secondary metabolite with relevance to virulence.

Original languageEnglish (US)
Pages (from-to)5905-5913
Number of pages9
JournalJournal of Bacteriology
Volume193
Issue number21
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

Multigene Family
Mycobacterium
Siderophores
Tuberculosis
Iron
Genes
Mycobacterium smegmatis
Horizontal Gene Transfer
Essential Genes
Sequence Analysis
Virulence
mycobactins
Genome
Bacteria

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Chavadi, S. S., Stirrett, K. L., Edupuganti, U. R., Vergnolle, O. M., Sadhanandan, G., Marchiano, E., ... Quadri, L. E. N. (2011). Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster. Journal of Bacteriology, 193(21), 5905-5913. https://doi.org/10.1128/JB.05811-11

Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster. / Chavadi, Sivagami Sundaram; Stirrett, Karen L.; Edupuganti, Uthamaphani R.; Vergnolle, Olivia M.; Sadhanandan, Gigani; Marchiano, Emily; Martin, Che; Qiu, Wei Gang; Soll, Clifford E.; Quadri, Luis E N.

In: Journal of Bacteriology, Vol. 193, No. 21, 11.2011, p. 5905-5913.

Research output: Contribution to journalArticle

Chavadi, SS, Stirrett, KL, Edupuganti, UR, Vergnolle, OM, Sadhanandan, G, Marchiano, E, Martin, C, Qiu, WG, Soll, CE & Quadri, LEN 2011, 'Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster', Journal of Bacteriology, vol. 193, no. 21, pp. 5905-5913. https://doi.org/10.1128/JB.05811-11
Chavadi SS, Stirrett KL, Edupuganti UR, Vergnolle OM, Sadhanandan G, Marchiano E et al. Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster. Journal of Bacteriology. 2011 Nov;193(21):5905-5913. https://doi.org/10.1128/JB.05811-11
Chavadi, Sivagami Sundaram ; Stirrett, Karen L. ; Edupuganti, Uthamaphani R. ; Vergnolle, Olivia M. ; Sadhanandan, Gigani ; Marchiano, Emily ; Martin, Che ; Qiu, Wei Gang ; Soll, Clifford E. ; Quadri, Luis E N. / Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster. In: Journal of Bacteriology. 2011 ; Vol. 193, No. 21. pp. 5905-5913.
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