Genome-wide Studies of Mycolic Acid Bacteria: Computational Identification and Analysis of a Minimal Genome

  • Frederick Kinyua Kamanu

Student thesis: Doctoral Thesis


The mycolic acid bacteria are a distinct suprageneric group of asporogenous Grampositive, high GC-content bacteria, distinguished by the presence of mycolic acids in their cell envelope. They exhibit great diversity in their cell and morphology; although primarily non-pathogens, this group contains three major pathogens Mycobacterium leprae, Mycobacterium tuberculosis complex, and Corynebacterium diphtheria. Although the mycolic acid bacteria are a clearly defined group of bacteria, the taxonomic relationships between its constituent genera and species are less well defined. Two approaches were tested for their suitability in describing the taxonomy of the group. First, a Multilocus Sequence Typing (MLST) experiment was assessed and found to be superior to monophyletic (16S small ribosomal subunit) in delineating a total of 52 mycolic acid bacterial species. Phylogenetic inference was performed using the neighbor-joining method. To further refine phylogenetic analysis and to take advantage of the widespread availability of bacterial genome data, a computational framework that simulates DNA-DNA hybridisation was developed and validated using multiscale bootstrap resampling. The tool classifies microbial genomes based on whole genome DNA, and was deployed as a web-application using PHP and Javascript. It is accessible online at A third study was a computational and statistical methods in the identification and analysis of a putative minimal mycolic acid bacterial genome so as to better understand (1) the genomic requirements to encode a mycolic acid bacterial cell and (2) the role and type of genes and genetic elements that lead to the massive increase in genome size in environmental mycolic acid bacteria. Using a reciprocal comparison approach, a total of 690 orthologous gene clusters forming a putative minimal genome were identified across 24 mycolic acid bacterial species. In order to identify new potential drug candidates against the pathogenic mycolic acid bacteria, a drug target analysis of the protein-coding genes, that are conserved across 15 pathogens, identified a total of 175 potential broad spectrum drug candidates. The activity of the predicted targets can be modified by a total of 306 chemical compounds, 34 of which have been approved by the Food and Drug Administration (FDA), for human treatment.
Date of AwardDec 2012
Original languageEnglish (US)
Awarding Institution
  • Computer, Electrical and Mathematical Sciences and Engineering
SupervisorVladimir Bajic (Supervisor) & John Archer (Supervisor)


  • Bioinformatics
  • Phylogeny
  • Mycolic Acid Bacteria
  • Genomics
  • Systematics

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