Identification of a Desaturase Involved in Mycolic Acid Biosynthesis in Mycobacterium smegmatis

Research output: Contribution to journalArticle

Authors

  • Albel Singh
  • Kiranmai Bhatt
  • Houdini H T Wu
  • Nagatoshi Fujiwara
  • Kanae Teramoto
  • Apoorva Bhatt

Colleges, School and Institutes

External organisations

  • School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.

Abstract

Mycolic acids are unique long chain fatty acids found in the cell walls of mycobacteria including the tubercle bacillus, Mycobacterium tuberculosis. The introduction of double bonds in mycolic acids remains poorly understood, however, genes encoding two potential aerobic desaturases have been proposed to be involved in this process. Here we show that one of these genes, desA1, is essential for growth of the saprophytic Mycobacterium smegmatis. Depletion of desA1 in a M. smegmatis conditional mutant led to reduction of mycolic acid biosynthesis and loss of viability. The DesA1-depleted cells exhibited two other phenotypes: using 14[C]-labelling, we detected the accumulation of minor mycolic acid-related species that migrated faster in a silver TLC plate. Spiral Time of Flight Mass Spectroscopic analysis suggested the presence of species with sizes corresponding to what were likely monoenoic derivatives of α-mycolic acids. Additionally, conditional depletion led to the presence of free fatty acyl species of lengths ~C26-C48 in the lysing cells. Cell viability could be rescued in the conditional mutant by Mycobacterium tuberculosis desA1, highlighting the potential of desA1 as a new drug target in pathogenic mycobacteria.

Details

Original languageEnglish
Article numbere0164253
JournalPLoS ONE
Volume11
Issue number10
Publication statusPublished - 14 Oct 2016